Percutaneous Coronary Intervention (PCI) 

Updated: Oct 11, 2016
Author: George A Stouffer, III, MD; Chief Editor: Karlheinz Peter, MD, PhD 


Practice Essentials

Percutaneous coronary intervention (PCI), also known as coronary angioplasty, is a nonsurgical technique for treating obstructive coronary artery disease, including unstable angina, acute myocardial infarction (MI), and multivessel coronary artery disease (CAD). See the image below.

Example of intravascular ultrasonography (IVUS) im Example of intravascular ultrasonography (IVUS) image in percutaneous transluminal coronary angioplasty (PTCA).

Indications and contraindications

Clinical indications for PCI include the following:

  • Acute ST-elevation myocardial infarction (STEMI)
  • Non–ST-elevation acute coronary syndrome (NSTE-ACS)
  • Unstable angina
  • Stable angina
  • Anginal equivalent (eg, dyspnea, arrhythmia, or dizziness or syncope)
  • High risk stress test findings

In an asymptomatic or mildly symptomatic patient, objective evidence of a moderate to large area of viable myocardium or moderate to severe ischemia on noninvasive testing is an indication for PCI. Angiographic indications include hemodynamically significant lesions in vessels serving viable myocardium (vessel diameter >1.5 mm).

Clinical contraindications for PCI include intolerance of long-term antiplatelet therapy or the presence of any significant comorbid conditions that severely limit the lifespan of the patient (this is a relative contraindication). A Heart Team approach (involving interventional cardiologists and cardiac surgeons) should be used in patients with diabetes and multivessel coronary artery disease and in patients with severe left main disease and a high Syntax score.

Relative angiographic contraindications include the following:

  • Arteries < 1.5 mm in diameter
  • Diffusely diseased saphenous vein grafts
  • Other coronary anatomy not amenable to PCI

In patients with stable angina, medical therapy is recommended as first-line therapy unless one or more of the following indications for cardiac catheterization and PCI or coronary artery bypass grafting (CABG) are present:

  • Severe symptoms
  • A change in symptom severity
  • Failed medical therapy
  • High-risk coronary anatomy
  • Worsening left ventricular (LV) dysfunction

For patients with STEMI, immediate coronary angiography with PCI is recommended (primary PCI).

For patients with NSTE-ACS, American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines on the management of NSTE-ACS (updated in 2014[1] ) recommend an early invasive strategy in most cases, with timing as follows:

  • Immediate (within 2 hours) - Patients with refractory angina,  recurrent angina after initial treatment, signs/symptoms of heart failure, new/worsening mitral regurgitation, hemodynamic instability, sustained ventricular tachycardia, or ventricular fibrillation
  • Early (within 24 hours) - None of the immediate characteristics but new ST-segment depression, a GRACE risk score >140, or temporal change in troponin
  • Delayed invasive (within 25-72 hours) - None of the immediate or early characteristics but renal insufficiency (glomerular filtration rate [GFR] < 60 mL/min/1.73 m 2), left ventricular ejection fraction (LVEF) < 40%, early postinfarct angina, history of PCI within the preceding 6 months, prior CABG, GRACE risk score of 109-140, or TIMI score of 2 or higher

Ischemia-guided approach is recommended for patients with a low-risk score (TIMI 0 or 1, GRACE < 109).

See Overview for more detail.


Balloon catheters for PCI have the following features:

  • A steerable guide wire precedes the balloon into the artery and permits navigation through the coronary tree
  • Inflation of the balloon compresses and axially redistributes atheromatous plaque and stretches the vessel wall
  • The balloon catheter also serves as an adjunctive device for many other interventional therapies

Atherectomy devices have the following features:

  • These devices are designed to physically remove coronary atheroma, calcium, and excess cellular material
  • Rotational or orbital atherectomy, which relies on plaque abrasion and pulverization, is used mostly for fibrotic or heavily calcified lesions that can be wired but not crossed or dilated by a balloon catheter
  • Atherectomy devices may be used to facilitate stent delivery in complex lesions
  • Directional coronary atherectomy (DCA) has been used to debulk coronary plaques
  • Laser atherectomy is not widely used at present
  • Atherectomy is typically followed by balloon dilation and stenting

Intracoronary stents have the following features:

  • Stents differ with respect to composition (eg, cobalt chromium or platinum chromium), architectural design, delivery system and the drug delivered
  • Drug-eluting stents (DESs) have demonstrated significant reductions in restenosis and target-lesion revascularization rates, with further reduction with the second-generation DESs (compared with first-generation DESs or bare-metal stents [BMSs])
  • In the United States, the commercially available DESs are second-generation models that elute everolimus and zotarolimus
  • Both stents with bioabsorbable polymer and fully bioresorbable scaffolds have been apprpoved by the FDA and are available for commercial use in the United States
  • Stents are conventionally placed after balloon predilation, but in selected coronary lesions, direct stenting may lead to better outcomes

Other devices used for PCI include the following:

  • Thrombus aspiration is no longer recommended as a routine practice in patients undergoing primary PCI; two large randomized trials showed no reduction in the rate of death from any cause or the composite of death from any cause, rehospitalization for myocardial infarction, or stent thrombosis [2]
  • Distal embolic protection during saphenous vein graft intervention can be considered when technically feasible

See Periprocedural Care and Devices for more detail.


Intravascular ultrasonography (IVUS) and optical coherence tomography (OCT) are used in PCI for the following purposes:

  • Provision of information about atherosclerotic plaque composition and burden, the vessel wall, vessel size, degree of calcium, and degree of luminal narrowing
  • Assessment of indeterminate lesions
  • Evaluation of adequate stent deployment

Intracoronary pressure wires are used in PCI as follows:

  • Characterization of coronary lesion physiology and estimation of lesion severity
  • Comparison of pressure distal to a lesion with aortic pressure enables determination of fractional flow reserve (FFR); FFR < 0.80 during maximal hyperemia (induced via administration of adenosine) is consistent with a hemodynamically significant lesion

Antithrombotic therapy

  • Aspirin 162-325 mg is given to all patients on the day of PCI
  • Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or bivalirudin may be used at the time of balloon angioplasty or PCI; fondaparinux must be supplemented with UFH to prevent catheter thrombosis and therefore is less commonly used

Antiplatelet therapy

Patients receiving stents are treated with a combination of aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor). The minimum duration of P2Y12 receptor inhibitor therapy, as per the current ACCF/AHA guidelines, is as follows:

  • BMSs - Minimum of 4 weeks
  • DESs (for acute coronary syndrome patients) - Minimum of 12 months
  • DESs (for stable ischemic heart disease patients) - Minimum of 6 months
  • DESs (for patients who are at high risk for bleeding) - Minimum of 3 months may be reasonable

Use of proton pump inhibitors (PPIs) is appropriate in patients with multiple risk factors for gastrointestinal bleeding who require antiplatelet therapy.

Glycoprotein inhibitor therapy

  • Abciximab, tirofiban, and eptifibatide have all been shown to reduce ischemic complications in patients undergoing balloon angioplasty and coronary stenting; however, evidence supporting their use was established largely before the use of oral P2Y12 inhibitors; all glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors are associated with an increased risk of bleeding
  • Several studies have failed to show the benefit of “upstream” administration of GPIIb/IIIa inhibitors in the era of dual antiplatelet therapy (DAPT); because GPIIb/IIIa inhibitors increase the risk of bleeding, their routine use before PCI is no longer recommended
  • GPIIb/IIIa inhibitors can be used as an adjunctive therapy at the time of PCI, on an individual basis, for large thrombus burden or inadequate P2Y12 receptor antagonist loading

See Technique and Medication for more detail.


Since the first human percutaneous transluminal coronary angioplasty (PTCA) procedure was performed in 1977, the use of percutaneous coronary intervention (PCI) has increased dramatically; it is now one of the most commonly performed medical interventions. Originally developed in Switzerland by Andreas Gruentzig, PCI has transformed the practice of revascularization for coronary artery disease (CAD).

Coronary angioplasty, initially used in the treatment of patients with stable angina and discrete lesions in a single coronary artery, currently has multiple indications, including unstable angina, acute myocardial infarction (AMI), and multivessel CAD. With the combination of sophisticated equipment, experienced operators, and modern drug therapy, PCI has evolved into an effective nonsurgical modality for treating patients with CAD. Ongoing technical advances are allowing more patients with chronic total occlusions (CTOs) to be successfully treated percutaneously.

Improvements in catheter technique and the development of new devices and medications have paralleled our growing understanding of cardiovascular physiology, the pathogenesis of atherosclerosis, and the response to vascular injury. Intracoronary stents and atherectomy devices have been developed to increase the success and decrease the complications of conventional balloon dilation, as well as to expand the indications for revascularization. Interventionalists now can safely treat more complex coronary lesions and restenosis.

The development of drug-eluting stents (DESs) has substantially reduced the problem of restenosis seen with bare-metal stents (BMSs). At the same time, advances in intravascular ultrasonography (IVUS), optical coherence tomography (OCT), and fractional flow reserve (FFR) evaluation have improved the understanding of coronary plaque morphology, plaque vulnerability, and coronary physiology.

Furthermore, many of these technologies are able to help identify patients who will benefit most from PCI, coronary artery bypass grafting (CABG), or medical therapy. Adjunctive pharmacologic therapies aimed at preventing acute reocclusion have also improved the safety and efficacy of PCI.

The growth of PCI has been remarkable. Stents are now used in more than 80% of PCI cases in the United States. This prominent use of stents will be sustained they result in improved outcomes. Over the past two decades, innovations in PCI have been paralleled by dramatic reductions in 30-day death, myocardial infarction (MI), and target-vessel revascularization rates. (See Unstable Angina.)


Clinical indications for PCI include the following:

  • Acute ST-elevation MI (STEMI)
  • Non–ST-elevation acute coronary syndrome (NSTE-ACS)
  • Stable angina
  • Anginal equivalent (eg, dyspnea, arrhythmia, or dizziness or syncope)
  • Asymptomatic or mildly symptomatic patient with objective evidence of a moderate-sized to large area of viable myocardium or moderate to severe ischemia on noninvasive testing

Angiographic indications include hemodynamically significant lesions in vessels serving viable myocardium (vessel diameter >1.5 mm).


Clinical contraindications for PCI include intolerance of chronic antiplatelet therapy and the presence of any significant comorbid conditions that severely limit patient lifespan (this is a relative contraindication). A Heart Team approach (involving interventional cardiologists and cardiac surgeons) should be used in patients with diabetes and multivessel CAD and in patients with severe left main disease and a high Syntax score.

Relative angiographic contraindications include the following:

  • Arteries < 1.5 mm in diameter
  • Diffusely diseased saphenous vein grafts
  • Other coronary anatomy not amenable to PCI

Although CABG has been considered the standard of care for patients with unprotected left main CAD (ie, patients without prior CABG or a patent graft to the left anterior descending [LAD] or left circumflex artery), PCI to improve survival is a reasonable alternative to CABG in selected stable patients who have ≥50% diameter stenosis and either of the following[3] :

  • Anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of good long-term outcome (eg, stenosis of the ostium or trunk vs distal bifurcation or trifurcation stenoses)
  • Clinical characteristics that predict a significantly higher risk of adverse surgical outcomes

In addition, the patient’s ability to tolerate and comply with dual antiplatelet therapy is a consideration in the choice of PCI rather than CABG.


In the focused update on appropriate use criteria published in 2012,[4] the use of coronary revascularization for patients with ACS and combinations of significant symptoms or ischemia was generally viewed favorably. However, the use of revascularization for asymptomatic patients or patients with low-risk findings on noninvasive testing and minimal medical therapy was viewed probably as unnecessary.

Same-day discharge after PCI

Rao et al examined the safety of same-day discharge in 107,018 low-risk patients 65 years or older who underwent elective PCI at 903 sites.[5] Only 1.25% of patients were discharged on the same day, and there was significant variation across facilities. Patients who were discharged on the same day had shorter procedures with less multivessel intervention. Notably, there were no significant differences between same-day discharge and overnight-stay patients with regard to mortality or rehospitalization rate either at 2 days or at 30 days.

Two meta-analyses that compared same-day discharge after elective PCI with overnight admission, including both radial and femoral approaches, showed no evidence for harm.[6, 7] Same-day discharge seems reasonable in carefully selected patients undergoing largely elective PCI.

PCI vs medical therapy: stable angina

Early trials demonstrated the advantages of PCI over medical therapy for symptomatic angina in single-vessel and multivessel CAD, with amelioration of symptoms, reduction of the need to take antianginal medications, improvement in exercise duration, and maintenance of survival rates comparable to those of medical therapy.[8, 9, 10]

There have been limited trials of coronary stenting versus medical therapy in patients with stable angina. Most of the data are derived from studies of balloon angioplasty vs medical therapy (eg, the RITA-II [Randomized Intervention in the Treatment of Angina][11] and AVERT [Atorvastatin Versus Revascularization Treatment][12] trials) or studies involving minimally symptomatic patients (eg, the COURAGE [Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation][13] trial).

The RITA-II study, in which 1018 patients with stable angina were randomized to balloon angioplasty or medical therapy, demonstrated that balloon angioplasty results in better control of ischemic symptoms and greater improvement in exercise capacity than medical therapy does, though balloon angioplasty was associated with an increased incidence of the combined endpoint of death and myocardial infarction.[11]

In this study, death or definite myocardial infarction occurred in 6.3% of the balloon angioplasty patients and in 3.3% of the medical patients; only 44% of the deaths were actually due to heart disease.[11] Angina improved in both groups, but a 16.5% absolute excess of grade 2 or worse angina was noted in the medical group 3 months after randomization.

In the medical group, 23% of patients required revascularization during follow-up.[11] In the angioplasty group, 7.9% of patients required bypass surgery during follow-up, compared with 5.8% in the medically treated group. It is important to emphasize that although the patients in RITA-II were asymptomatic or mildly symptomatic, most had severe anatomic CAD: 62% had multivessel CAD, and 34% had important disease of the proximal LAD artery.

In the AVERT trial, 13% of the medically treated group and 21% of the angioplasty group had ischemic events at 18 months, suggesting that in low-risk patients with stable CAD, aggressive lipid-lowering therapy may reduce ischemic events as effectively as balloon angioplasty does.[12] A total of 341 patients with stable CAD symptoms, normal left ventricular (LV) function, and class I or II angina were assigned randomly to balloon angioplasty or atorvastatin therapy.

On the basis of the limited data available from randomized trials comparing medical therapy with balloon angioplasty, it seems appropriate to consider medical therapy for initial management of most patients with Canadian Cardiovascular Society Classification class I and II symptoms and to reserve percutaneous or surgical revascularization for patients with more severe symptoms and ischemia.

The COURAGE trial demonstrated that in patients with minimal, stable angina symptoms and coronary artery stenosis, medical therapy alone may be an appropriate strategy if such therapy can control the angina symptoms.[13] The trial randomized the addition of PCI to intensive pharmacologic therapy, with the endpoints of death from any cause and nonfatal MI during a median follow-up period of 4.6 years.

It is important to emphasize that all patients in the COURAGE study underwent coronary angiography. Inclusion criteria included the presence of a 70% or greater lesion in 1 or more proximal epicardial arteries, American College of Cardiology (ACC)/American Heart Association (AHA) class I or II indications for PCI, and objective evidence of myocardial ischemia on stress testing.[13] For both primary endpoints, there was no statistically significant difference between patients who received PCI with medical therapy and those who received only medical therapy.

The COURAGE trial has been heavily criticized on several grounds, including the following:

  • All patients underwent coronary angiography before enrollment
  • Only one in 12 patients who were screened were actually enrolled
  • At the time of enrollment, most patients were either asymptomatic or had minimal symptoms

Teo et al found that in older patients with stable CAD, optimal medical treatment without PCI remains an appropriate initial management strategy.[13] Analysis of 904 patients aged 65 years or older showed that, during a median 4.6-year follow-up, clinical outcome was no better or worse in patients randomized to optimal medical treatment plus PCI than in patients who received optimal medical treatment alone.

Compared with 1381 patients younger than 65 years with CAD, older patients had similar success in achieving treatment targets and similar rates of myocardial infarction, stroke, and major cardiac events, though the death rate was two to three times higher in the older patients.[13] It should be kept in mind that the analysis was done from patients enrolled in the COURAGE trial and thus must be interpreted in terms of the limitations outlined above.

Overall, medical therapy is recommended as first-line therapy in patients with stable angina unless one or more of the following indications for cardiac catheterization and PCI or CABG are present:

  • Severe symptoms
  • A change in symptom severity
  • Failed medical therapy
  • High-risk coronary anatomy or noninvasive findings
  • Worsening LV dysfunction

PCI vs surgical revascularization: stable angina

Two prospective clinical trials evaluated balloon angioplasty against surgery for revascularization of isolated LAD artery disease.[14, 15]

Using a combined endpoint (cardiac death, myocardial infarction, or refractory angina necessitating revascularization by surgery), the MASS (Medicine, Angioplasty, or Surgery Study) trial showed that after 3 years of follow-up, endpoint events occurred in 24% of angioplasty patients, 17% of medical patients, and 3% of surgical patients.[14] However, overall survival rates were similar in the three groups.

The other trial evaluated balloon angioplasty against bypass surgery with an internal thoracic (mammary) artery graft to the LAD artery and also reported no difference in survival during follow-up.[15] Although 94% of angioplasty patients and 95% of bypass patients were free of limiting symptoms, the former required more antianginal drugs. At 2.5 years’ follow-up, 86% of surgery patients were free from late events, compared with 43% of angioplasty patients. This difference was primarily due to restenosis necessitating a second revascularization procedure.

It is important to emphasizing that balloon angioplasty, rather than stent placement, was used in both of these trials; with the almost exclusive use of stenting in the current era, restenosis rates are now lower.

Five large (N > 300) randomized trials comparing balloon angioplasty with bypass surgery in patients with multivessel CAD all showed that in appropriately selected patients, the rates of death or of MI were similar, regardless of which treatment was employed.[16, 17, 18, 19, 20] However, more of the angioplasty-treated patients required a second revascularization procedure. Three of these studies are summarized in Table 1 below.

Table 1. Comparison of Surgical Therapy and Coronary Angioplasty (Open Table in a new window)


Pocock et al*

Pocock et al†

BARI Study‡













Death (%)







Death or MI







Repeat CABG







Repeat CABG or PTCA







More than mild angina







*Meta-analysis of results of 3 trials at 1 year. Patients with single-vessel disease were studied.[20]

†Meta-analysis of results of 3 trials at 1 year. Patients with multivessel disease were studied.[20]

‡Reported results are for 5-year follow-up. Patients with multivessel disease were studied.[19]

§ P < .05.

BARI = Bypass Angioplasty Revascularization Investigation; CABG = coronary artery bypass grafting; MI = myocardial infarction; PTCA = percutaneous transluminal coronary angioplasty.

In the BARI (Bypass Angioplasty Revascularization Investigation) study, 5-year survival was 86.3% for those assigned to angioplasty versus 89.3% for those assigned to surgery, and 5-year freedom from Q-wave MI was 78.7% for the former and 80.4% for the latter.[19] However, after 5 years of follow-up, 54% of those assigned to angioplasty required an additional revascularization procedure, compared with only 8% of those assigned to surgery.

Similarly, the ERACI (Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Multivessel Disease) study showed that freedom from combined cardiac events at 3 years was significantly better for bypass surgery than for angioplasty (77% vs 47%), though the groups did not differ in terms of overall and cardiac mortality or frequency of MI.[21] Bypass patients were more often free of angina (79% vs 57%) and had fewer additional revascularization procedures (6% vs 37%).

In most patient subgroups with multivessel CAD, long-term mortality after CABG is comparable to that after PCI; therefore, the choice of treatment should depend on patient preference. In a collaborative analysis of individual patient data from 10 randomized trials, Hlatky et al found CABG to be a superior option for patients with diabetes and patients aged 65 years or older because mortality was lower in these subgroups.[22, 23]

Bare-metal stents vs CABG

The major limitations of balloon angioplasty were acute vessel closure and restenosis. Early studies with intracoronary stents showed that these devices were highly effective for treating or preventing acute or threatened vessel closure and thereby avoiding emergency bypass surgery.

Two randomized trials, BENESTENT (Belgian Netherlands Stent)[24] and STRESS (Stent Restenosis Study),[25] demonstrated that coronary stenting of de novo lesions in native vessels reduced angiographic restenosis by approximately 30% as compared with conventional balloon angioplasty. Stenting produces a larger lumen diameter than conventional balloon angioplasty both immediately after the procedure (acute gain) and at follow-up (net gain), resulting in less restenosis.

The use of BMSs was compared to bypass surgery for the treatment of multivessel CAD in the ARTS (Arterial Revascularization Therapies Study) trial.[26] After 1 year of follow-up, no difference was noted between the groups in the rate of death, stroke, or MI. Event-free survival was better in the surgery group than in the stent group (87.8% vs 73.8%), and only 3.5% in the surgery group required a second revascularization procedure, compared with 16.8% in the stent group.

The SoS (Stent or Surgery) trial compared BMSs with CABG and reported a 2-year target vessel revascularization rate of 21% in stent patients, compared with 6% in CABG patients.[27] Death and MI rates were similar in the two groups. However, the SoS trial had a higher noncardiac death rate in the PCI arm, thought to be attributed to a type II error that may have affected the study results.

The SoS trial and the ARTS study demonstrate the safety of PCI treatment in multivessel disease. Cardiac mortality risk is low, and the rates of repeat target vessel revascularization are less than half of those seen with balloon angioplasty.[28]

According to the New York Cardiac Registry, as with the prior trials, patients who received PCI as the initial therapy had a higher incidence of target vessel revascularization (35.1%) than those who received CABG (4.9%).[29] The registry identified 59,314 patients with multivessel disease who either underwent CABG (n = 37,212) or had PCI with bare-metal stents (n = 22,102), with reported endpoints of repeat revascularization and survival rates within 3 years.

Using unadjusted survival curves, the registry demonstrated that for patients who had two-vessel disease without LAD artery involvement, PCI offered a small survival benefit.[29] For patients who had two-vessel disease with proximal LAD artery involvement, the two procedures had similar mortalities (91.4% for CABG and 91.2% for PCI). The registry reported a statistically significant survival benefit of CABG over PCI in patients who had three-vessel disease with proximal LAD artery involvement.

Drug-eluting stents vs CABG

In the ARTS II trial, a registry comparing the use of sirolimus-eluting stents (SESs) with the PTCA and CABG arms of the ARTS I trial, SESs were associated with an 8% major cardiovascular event (MACE) rate (vs 13% for CABG in ARTS I) and an 8.5% target vessel revascularization rate (vs 4% for CABG and 21% for PTCA in ARTS I). The 1-year MACE rate was 10.5% for SES patients.[30]

The New York Cardiac Registry found that patients who underwent PCI with a DES had a higher rate of target vessel revascularization than those who underwent CABG (30.6% vs 5.2%).[29] They analyzed 17,400 patients who either received a DES (n = 9963) or underwent CABG (n = 7437) and observed them for 18 months. Unadjusted survival curves did not demonstrate a statistical significance in survival for two- or three-vessel disease.

Nevertheless, when adjustments were made for several factors (ie, age; sex; ejection fraction; hemodynamic state; history or no history of MI before the procedure; the presence or absence of cerebrovascular disease, peripheral arterial disease, congestive heart failure, chronic obstructive pulmonary disease [COPD], diabetes, and renal failure; and involvement of the proximal LAD artery), CABG had a statistically significant 18-month survival benefit over PCI with a DES.[29]

The SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) study was a large randomized controlled trial that enrolled 1800 patients with multi-vessel CAD to receive either a paclitaxel-eluting stent or CABG.[31]

At 5 years, the major adverse cardiac and cerebrovascular events (MACCE)—a composite of death, stroke, MI, or repeat revascularization—was significantly higher in patients with PCI than in those with CABG (37.5% vs 24.2%).[31] PCI, as opposed to CABG, resulted in significantly higher rates of all-cause death (14.6% vs 9.2%), MI (9.2 vs 4.0%), and repeat revascularization (25.4% vs 12.6%); however, the rate of stroke was similar.

In this trial, the extent of CAD was assessed by using a SYNTAX score that was based on location, severity, and degree of stenosis.[31] In patients with a low (0-22) SYNTAX score, PCI and CABG resulted in similar rates of MACCE (33.3% vs 26.8%) but PCI was associated with significantly more repeat revascularization (25.4% vs 12.6%). In patients with intermediate (23-32) or high (≥33) SYNTAX scores, CABG demonstrated clear superiority, with lower rates of MACCE, all-cause death, MI, and repeat revascularization.

In conclusion, the SYNTAX trial suggested that in patients with multivessel CAD, survival rates with CABG and PCI are comparable in patients with relatively uncomplicated and lesser degrees of CAD.[31] However, in patients with complex and diffuse CAD, CABG appears to be preferable. One caveat to be remembered is that the SYNTAX trial used first-generation paclitaxel-eluting stents. These stents have a higher rate of restenosis than the currently used second-generation DESs.

In summary, in deciding between PCI and CABG in patients with complex multivessel CAD, a Heart Team approach is recommended.

Diabetics with multivessel coronary artery disease

Patients with diabetes mellitus appear to constitute an exception to the general findings that balloon angioplasty and bypass surgery yield essentially equivalent results in patients with multivessel disease.

Among diabetic patients in the BARI trial, 5-year survival was 65.5% in those treated by balloon angioplasty and 80.6% for those treated with bypass surgery.[19] The improved survival with surgery was due to reduced cardiac mortality (5.8% vs 20.6%) and was confined to those receiving at least one internal thoracic artery graft. Better survival among diabetic patients with multivessel disease treated with bypass surgery rather than angioplasty was also observed in a large retrospective study.

The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial randomized 2364 men and women with type 2 diabetes mellitus, documented CAD, stable symptoms, and myocardial ischemia treated with optimal medical therapy to an initial strategy of either coronary revascularization or watchful waiting with the option of subsequent revascularization.[32] At 5 years, rates of survival or the composite endpoint of cardiovascular death, MI, and stroke did not differ significantly between the groups.

A substudy of the BARI 2D trial reported that the coronary revascularization strategy improved outcomes at the 3-year follow-up, with patients experiencing a lower rate of worsening angina, new angina, and subsequent coronary revascularizations, as well as a higher rate of angina-free status.[33]

The FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus Optimal Management of Multivessel Disease) trial randomly assigned 1900 patients with diabetes and multivessel CAD to either PCI with a DES or CABG. At 5 years, the rate of primary outcome—a composite of death, nonfatal MI, or nonfatal stroke—was lower in the CABG group (18.7%) than in the DES group (26.6%). CABG also had lower rates of death (10.9% vs 16.3% for PCI) and MI (6.0% vs 13.9% for PCI) but higher rates of stroke (5.2% vs 2.4% for PCI).[34]

A meta-analysis of 3131 patients from eight randomized, controlled trials (including SYNTAX and FREEDOM) that compared CABG with PCI in patients with diabetes suggested that all-cause mortality was lower with CABG than with PCI.[35]

In summary, in deciding between PCI and CABG in patients with diabetes mellitus and complex multivessel CAD, a Heart Team approach is recommended. CABG is generally recommended in preference to PCI, provided that the patient is a good candidate for surgery, there is extensive CAD (eg, three-vessel CAD or complex two-vessel CAD involving the proximal LAD artery), and the LAD artery can be anastomosed with a left internal mammary artery (LIMA) graft, CABG is generally recommended in preference to PCI.

PCI in NSTE-ACS (unstable angina and non-STEMI)

The management of patients with non-STEMI (NSTEMI) and unstable angina (called NSTE-ACS in the 2014 ACC/AHA guideline update to reflect the similarity between the two groups) has changed considerably over the past 15 years.[1] Several trials have helped provide a better understanding of risk stratification, selection of initial management strategy, and appropriate use of adjunctive medical therapy and revascularization, thereby leading to improved outcomes.

In general, two pathways have emerged for the treatment of NSTE-ACS. The early invasive strategy, with a diagnostic coronary angiogram for risk stratification, allows rapid definitive evaluation and affords the option for early revascularization to prevent ACS complications and facilitate early discharge.

In contrast, the ischemia-guided strategy (previously termed conservative strategy) recommends invasive evaluation only if patients have failed medical therapy, have objective evidence of ischemia on stress test, or have high prognostic risk (ie, high Thrombolysis in Myocardial Infarction [TIMI] or Global Registry of Acute Coronary Events [GRACE] scores). This is based on the premise that medical therapy alone can stabilize some patients, thus obviating costly and possibly unnecessary invasive procedures.

In terms of outcome data, several studies have assessed the use of an ischemia-guided strategy against the use of an early invasive strategy of revascularization

The VANQWISH (Veterans Affairs Non–Q-Wave Infarction Strategies in Hospital) trial compared an invasive strategy with conservative medical treatment in patients with non–Q-wave MI and found that the rates of death or nonfatal MI were higher in the invasive strategy group than in the conservative strategy group before hospital discharge, at 1 month, and at 1 year.[36]

Criticisms of this study include the exclusion of patients at very high risk; the lack of current aggressive medical therapies; a high rate of crossover to angiography in the conservative arm; a higher surgical mortality than expected in view of with contemporary standards; and the observation that most of the complications at 30 days occurred in patients who underwent CABG, with very few occurring in those who underwent balloon angioplasty.[36]

In contrast to the VANQWISH trial, four randomized studies found that an early invasive approach in patients with ACS was associated with improved outcomes.

The TIMI IIIb study showed less ischemia, shorter hospital stays, fewer readmissions, and fewer symptoms in patients treated by an early invasive approach.[37]

The FRISC (Fragmin and Fast Revascularization during Instability in Coronary Artery Disease) II trial prospectively randomized 2457 patients to receive either early invasive treatment with intracoronary stenting or noninvasive treatment and found that at 6 months, the composite endpoint of death or MI was higher in the latter arm than in the former.[38] Additionally, symptoms of angina and hospital readmissions were twice as common in the noninvasive arm as in the invasive arm.

The RITA-III study reported improved outcomes with early invasive therapy in 1810 patients at 5 years’ follow-up.[39] There was a statistically significant difference favoring an interventional strategy over conservative therapy with respect to all-cause mortality (15.1% vs 12.1%) and the rate of cardiac death or MI (15.9% vs 12.2%).

Data from the TACTICS-TIMI (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy–Thrombolysis in Myocardial Infarction) 18 trial showed that the primary endpoint of death, MI, or rehospitalization at 6 months occurred in 19.4% of the conservative group and 15.9% of the invasive group, with death or MI occurring in 9.5% and 7.3%, respectively.[40]

In this study, patients who had a positive troponin test result, those who had ST-segment changes, those who were older than 65 years, and, especially, those who were women with elevated brain natriuretic peptide (BNP) and C-reactive protein (CRP) levels derived particular benefit from an early invasive strategy.[40]

The ICTUS (Early Invasive versus Selectively Invasive Management for Acute Coronary Syndromes) trial, which compared an early invasive strategy (angiography and revascularization within 48 hours) with a selective invasive strategy (medical stabilization with angiography and revascularization in refractory cases) in 1200 Dutch patients, demonstrated no statistical difference in mortality or the composite endpoint (death, nonfatal MI, or rehospitalization for anginal symptoms within 1 year).[41]

At 3 years’ follow-up, the ICTUS trial documented a trend toward significance favoring the selective invasive strategy for the combined endpoints (30% early invasive vs 26% selective invasive) but reported no differences in all-cause mortality and cardiac death. Overall, the weight of evidence has favored early invasive therapy over the ischemia-guided strategy, with one collaborative meta-analysis of randomized trials showing an 18% relative reduction in death or MI.[42] The invasive arm was also associated with less angina and fewer hospitalizations.

In a meta-analysis of patient-level data from FRISC, ICTUS, and RITA trials, 14.7% of patients treated according to the early invasive strategy had cardiovascular death or nonfatal MI, versus 17.9% in the selective invasive group.[43] Absolute risk reduction of cardiovascular death and nonfatal MI was 2-3.8 % in the low-to-intermediate group and 11.1% in the highest-risk patient.

With respect to the timing of the invasive strategy, some studies have demonstrated the benefit of early angiography,[44] particularly in high-risk patients (GRACE >140). A more delayed strategy is reasonable in low-to-intermediate risk patients. Two meta-analyses showed that whereas the early invasive approach yields no survival benefit or reduction in recurrent MI or major bleeding rates, it also poses no early hazard and has the advantages of less recurrent ischemia and a shorter hospital stay.[45, 46]

The 2014 ACC Foundation/AHA guidelines for management of unstable angina/NSTEMI recommend the use of an early invasive strategy or ischemia-guided strategy in patients with NSTE-ACS. An ischemia-guided approach is recommended for patients with a low-risk score (TIMI 0 or 1, GRACE < 109). Other patients will benefit from an early invasive strategy stratified by timing as follows:

  • Immediate (within 2 hours) - Patients with refractory or recurrent angina with initial treatment, signs/symptoms of heart failure, new/worsening mitral regurgitation, hemodynamic instability, sustained ventricular tachycardia, or ventricular fibrillation
  • Early (within 24 hours) - None of the immediate characteristics but new ST-segment depression, a GRACE risk score > 140, or temporal change in troponin
  • Delayed invasive (within 25-72 hours) - None of the immediate or early characteristics but renal insufficiency (Glomerular filtration rate [GFR] < 60 mL/min/1.73 m 2), left ventricular ejection fraction (LVEF) < 40%, early postinfarct angina, history of PCI within the past 6 months, prior CABG, GRACE risk score of 109-140, or TIMI score of 2 or higher

PCI in acute ST-elevation myocardial infarction (STEMI)

The recognition that intracoronary thrombosis from a ruptured plaque is the primary cause of vessel occlusion in STEMI and that prompt restoration of vessel patency provides significant clinical benefit has led to the development of two main reperfusion strategies.

Thrombolytic therapies, such as front-loaded tissue plasminogen activator (t-PA), reteplase (r-PA), and tenecteplase (TNK), open approximately 60-80% of infarct-related vessels within 90 minutes, but only 50% of these vessels will have normal (TIMI grade 3) flow. In addition, 10% of vessels opened by thrombolysis either become reoccluded or are the source for recurrent symptoms of angina. Also, patients older than 75 years, who have the most to gain from reperfusion, have unacceptably high rates of intracerebral hemorrhage with thrombolysis.

Because of these limitations, several randomized trials have evaluated mechanical revascularization with primary angioplasty in the setting of STEMI. The advantage of this approach is that the artery can be opened more frequently (>95%), and the underlying plaque rupture can be treated.

An analysis of 23 trials confirmed the superiority of primary angioplasty to thrombolytic therapy in terms of adverse events and mortality reduction, both in the short term and in the long term. Overall, primary PCI was associated with significant reductions in death, recurrent MI, reinfarction, and the combined endpoint of death, MI, and stroke.[47]

Subsequent studies showed the importance of rapid reperfusion. Rathore et al, in a prospective cohort study of 43,801 patients enrolled in the ACC National Cardiovascular Data Registry in 2005-2006, found that any delay in primary PCI after a patient with STEMI arrives at the hospital is associated with higher mortality.[48]

In this study, longer door-to-balloon times were associated with a higher adjusted risk of in-hospital mortality, in a continuous nonlinear fashion (30 min = 3%, 60 min = 3.5%, 90 min = 4.3%, 120 min = 5.6%, 150 min = 7%, 180 min = 8.4%).[48] A reduction in door-to-balloon time from 90 minutes to 60 minutes was associated with a 0.8% reduction in mortality, and a reduction from 60 minutes to 30 minutes was associated with a 0.5% reduction in mortality.

Brodie et al, analyzing the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial and the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial, found that a door-to-balloon time of less than 90 minutes was associated with a lower mortality in patients with STEMI; however, the benefit was primarily noted in patients who presented with less than 90 minutes of symptoms.[49]

In this study, a door-to-balloon time shorter than 90 minutes was associated with similar relative risk reductions in high-risk and low-risk patients, though the absolute benefit was greatest in high-risk patients.[49]

The salient recommendations from the 2013 update of the ACCF/AHA STEMI guidelines, which were written in collaboration with the PCI guideline writing group, are as follows[2] :

  • Emergency medical services should transport patients directly to a PCI-capable hospital for primary PCI, with an ideal goal of a first medical contact (FMC)-to-device time of 90 minutes or less
  • Non–PCI-capable hospitals should immediately transfer patients to a PCI-capable hospital, with an FMC-to-device goal of 120 minutes or less; the concept of door-in-door-out time is discussed, and whereas no specific time frame is set, it is emphasized that a time of ≤30 minutes (associated with lower in-hospital mortality), is achieved in only 11% of patients; factors to improve (shorten) treatment time for PCI-treated patients include use of prehospital electrocardiography (ECG) to diagnose STEMI, emergency physician activation of the PCI team, use of a central paging system to activate the PCI team, and establishing a goal of having the PCI team arrive in the catheterization laboratory within 20 minutes of being paged
  • Primary PCI is indicated (class I) in patients with ischemic symptoms < 12 hours and contraindications to thrombolytic therapy (irrespective of the time delay from FMC), patients with cardiogenic shock, and patients with acute severe heart failure (irrespective of the time delay from MI onset); primary PCI is reasonable (class IIa) in patients with ongoing ischemia 12-24 hours after symptom onset

When thrombolytic therapy is used as the primary reperfusion strategy in a non–PCI-capable facility, the goal remains administration of such therapy within 30 minutes of hospital arrival. Whereas a great deal of research has been devoted to comparing primary PCI, facilitated PCI, and thrombolytic strategies, the guidelines emphasize that “the appropriate and timely use of some form of reperfusion therapy is likely more important than the choice of therapy.”

The use of thrombolytic therapy followed by referral for intentional PCI (facilitated PCI) has not been shown to be superior to primary PCI and may actually worsen outcomes, with increased risk of stroke and bleeding (ASSENT 4). However, urgent transfer to a PCI-capable hospital for coronary angiography and possible “rescue PCI” is reasonable for STEMI patients with failed reperfusion or reocclusion after thrombolytic therapy.[2] Indeed, the term facilitated PCI is now considered obsolete.

The recommended strategy for thrombolysis is a full dose of a thrombolytic, aspirin, clopidogrel, and immediate transfer to a PCI-capable facility.

On the basis of the OAT (Occluded Artery Trial) data, delayed PCI of a totally occluded infarct artery more than 24 hours after STEMI should generally not be performed in most asymptomatic patients.[50]

PCI of a noninfarct artery at the time of PCI in patients without hemodynamic compromise is classified as a “class III – harm” recommendation and should not be performed.

Trials are planned that will assess the risks and benefits of complete revascularization at the time of STEMI. The treatment of non–infarct-related artery in STEMI and cardiogenic shock remains a controversial area, with some evidence of benefit for revascularization.[51]

Current STEMI guidelines recommend the use of a GPIIb/IIIa inhibitor (class IIa abciximab, tirofiban or eptifibatide) at the time of primary PCI in selected patients who are receiving unfractionated heparin (those who have a large thrombus burden or inadequate P2Y12 receptor antagonist loading). Routine use of GPIIb/IIIa inhibitors with bivalirudin is not recommended and may be considered as an adjunctive or “bailout” strategy in selected cases.

Intracoronary abciximab administration, in comparison with the intravenous (IV) standard route, can improve short-term clinical outcomes in patients with STEMI undergoing primary PCI.

A pooled analysis of individual data of 1198 patients enrolled in five trials showed that intracoronary abciximab administration, as compared with IV abciximab, significantly reduced the risk of the composite of death and reinfarction and death. After correction for baseline differences, there were no significant differences in target vessel revascularization or the risk of reinfarction.[52]

However, most of the evidence for these drugs was obtained in the era before early dual antiplatelet therapy (DAPT). A later randomized trial using bivalirudin and either prasugrel or clopidogrel in 452 patients with an anterior STEMI reported an improvement in infarct size (17.9% vs 15.1%) with intracoronary abciximab use.[53]

Stone et al studied the safety and efficacy of DESs and BMSs in 3006 patients with STEMI who underwent primary PCI.[16] Patients were assigned in a 3:1 ratio to receive paclitaxel-eluting stents or otherwise identical BMSs. The paclitaxel-eluting stents significantly reduced angiographic evidence of restenosis and recurrent ischemia necessitating repeat revascularization at 12-month follow-up. The rates of death and stent thrombosis were similar for the two groups.

The STEMI guidelines recommend 1 year of P2Y12 inhibitor therapy for patients who receive a BMS or a DES with clopidogrel, prasugrel, or ticagrelor.


From a procedural perspective, because primary PCI involves a thrombotic plaque, there is a potential for thrombotic complications including no-reflow and distal embolization. In these patients, there is some evidence that stenting plus GPIIb/IIIa inhibition will improve outcomes, as well as reduce target vessel revascularization and MI rates.

An analysis of 291,380 patients with AMI who underwent PCI of native coronary artery stenoses showed that no-reflow developed in 2.3%. Risk factors included older age, STEMI, prolonged interval from symptom onset to admission, and cardiogenic shock.[54] Angiographic factors associated with no-reflow included longer lesion length, class C lesions, bifurcation lesions, and impaired preprocedural TIMI flow. No-reflow was associated with greater in-hospital mortality. The authors concluded that no-reflow, though uncommon, is associated with adverse clinical outcomes.

Of interest has been the recognition that failure of complete reperfusion based on myocardial blush grade or incomplete ST-segment resolution (~50 % of patients with primary PCI) is associated with poorer outcomes despite normal epicardial flow. Efforts to reduce distal embolization using several strategies have been developed. Despite early promise from mechanical aspiration devices, intracoronary GPIIb/IIIa inhibitor use, and stent-based exclusion (Mesh Guard), none of these approaches has been proved to offer definitive benefit.


Periprocedural Care


Initially, percutaneous coronary intervention (PCI) was accomplished with balloon catheters. As a result of the technical challenges of percutaneous coronary artery balloon angioplasty, suboptimal clinical outcomes, and significant rates of restenosis after the procedure, two innovative types of devices were developed: atherectomy devices and coronary stents.

Long-term outcomes from atherectomy alone have been disappointing and, in most cases, little better than those from balloon angioplasty. Stents, particularly stents that elute medications that reduce inflammatory and cell growth responses, have resulted in greatly improved outcomes. Atherectomy is still used for specific niche indications, but the most common intracoronary device used today is a stent.

Various ancillary devices are also used for PCI.

Balloon catheters

The original description of angioplasty by Dotter and Judkins described enlargement of the vessel lumen through a mechanism of atheromatous plaque compression. This mechanism is also partially responsible for luminal enlargement with balloon angioplasty.

In addition, however, the increase in luminal diameter after balloon angioplasty also results from stretching of the vessel wall by the balloon. Balloon inflation actually results in overstretching of the vessel wall and partial disruption of not only the intimal plaque but also the media and adventitia, resulting in enlargement of the lumen and the outer diameter of the vessel.

Axial redistribution of plaque material also contributes to improvements in lumen diameter. Atherectomy devices and, subsequently, intracoronary stents were developed, in part, to decrease the early and late loss in luminal diameter observed with conventional balloon angioplasty.

Several different balloon catheter designs have existed (eg, over-the-wire, monorail, and fixed wire) and have used balloon materials with different compliance characteristics that allow varying degrees of expansion with increasing pressure. Irrespective of the balloon design, a steerable guide wire precedes the balloon into the artery and permits navigation through a considerable portion of the coronary tree.

The development of bending capability, allowing easy advancement through tortuous vascular segments (trackability), as well as increased shaft stiffness (pushability), allowing the catheter to be forced through stenotic lesions, has significantly increased the versatility of balloon catheters. Another evolving feature of catheter design has been a reduction in the diameter of the deflated balloon, allowing easier passage through very stenotic lesions.

Improvements in catheter design have been partially responsible for the improved success rates of PCI. The balloon catheter also serves as an adjunctive device for many other interventional therapies, including atherectomy and coronary stenting.

Atherectomy devices

Atherectomy devices were developed to permit drilling, grinding, or sanding of atheroma, calcium, and excess cellular material from the site of a coronary occlusion or stenosis. Both mechanical and laser-based approaches are used.

The rotational atherectomy catheter (Rotablator) is designed for the removal of plaque from coronary arteries. This device (see the image below), which has a diamond-studded burr at its tip, rotates at about 160,000 revolutions per minute (rpm) and is particularly well suited for ablation of calcific or fibrotic plaque material.

Percutaneous transluminal coronary angioplasty (PT Percutaneous transluminal coronary angioplasty (PTCA). Rotational atherectomy catheter (Rotablator) is designed for removal of plaque from coronary arteries. This device has diamond-studded burr at its tip, rotates at about 160,000 rpm, and is particularly well suited for ablation of calcific or fibrotic plaque material.

Unlike other atherectomy devices that rely on tissue cutting, the rotational atherectomy device relies on plaque abrasion and pulverization. Rotational atherectomy is successful in 92-97% of these cases, with a low incidence of major complications. It causes dislodgment of particles into the microcirculation, which occasionally may lead to infarction and no-reflow (impaired distal coronary flow). Currently, the use of rotational atherectomy is largely confined to fibrotic or heavily calcified lesions that can be wired but not crossed or dilated by a balloon catheter.

The ERBAC (Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison) Study showed that rotational atherectomy was associated with a higher short-term success rate than balloon angioplasty (90% vs 80%) was but that rates of major ischemic complications and repeat revascularization were higher 6 months after treatment (46% vs 37%).[55]

A meta-analysis failed to show any significant differences in mortality, major adverse cardiovascular events (MACE), or revascularization rates in patients treated with rotational atherectomy, laser, or cutting balloon angioplasty in comparison with balloon angioplasty alone.[56] In some cases, rotational atherectomy was actually associated with an increase in periprocedural myocardial infarction (MI).

However, none of these trials compared stent-related outcomes. In fact, many of these devices may be used to facilitate stent delivery in complex lesions, especially when balloon angioplasty alone has failed.

Beginning in 1987, directional coronary atherectomy (DCA) was used to debulk coronary plaques. In this procedure, a steel fenestrated cage housing a cup-shaped blade is positioned against the coronary lesion by a low-pressure positioning balloon, allowing any protruding plaque to be removed.

Complications (eg, distal embolization of plaque, transient side-branch occlusion, coronary vasospasm, the no-reflow phenomenon, non–Q-wave MI) are more frequent with DCA than with balloon angioplasty. Because of the increased complication rates and the greater technical demands of DCA as compared with balloon angioplasty or stenting, the use of DCAs has greatly decreased in recent years.

A 2006 meta-analysis demonstrated that DCA was superior to stenting alone with regard to acute angiographic results and target-lesion revascularization, with a similar prevalence of late MACE. There was, however, a higher prevalence of early MACE with DCA before stenting, which was probably related to distal embolization.[57]

Although the development of laser atherectomy generated considerable initial excitement, the procedure is not widely used at present, because of the technical demands imposed by the device and the lack of any clear improvements in outcome versus other devices.

Orbital atherectomy has only come into clinical use relatively recently. Orbital atherectomy utilizes an eccentrically mounted “crown” that is diamond-coated and rotates at speeds ranging from 60,000 to 200,000 rpm. Unlike the rotational atherectomy device, the orbital atherectomy crown is eccentric in shape and therefore has an elliptical orbit rather than spinning concentrically on the wire.

The ORBIT (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) II trial was a prospective single-arm multicenter study designed to evaluate orbital atherectomy for vessel preparation before stent implantation in severely calcified lesions.[58]  A total of 443 patients were enrolled, and the median follow-up was 25.1 months. The 2-year outcomes were reported as follows:

  • MACE, 19.4%
  • Death, 7.5%
  • Cardiac death, 4.3%
  • Target vessel revascularization, 8.1%
  • Target lesion revascularization (TLR), 6.2%

These rates were lower than those previously reported with alternative strategies. However, they once again highlighted detrimental effects of severe calcium in coronary revascularization. As expected, the TLR rate was threefold higher with bare-metal stents (BMSs) than with drug eluting stents (DESs), making the use of a DES more attractive in these circumstances.[58]

Intracoronary stents

Intracoronary stents have been used widely since the early 1990s. Various stents are available, differing with respect to composition (eg, cobalt chromium or platinum chromium), architectural design, and delivery system (see the images below).

Percutaneous transluminal coronary angioplasty (PT Percutaneous transluminal coronary angioplasty (PTCA). TRISTAR stent.
Percutaneous transluminal coronary angioplasty (PT Percutaneous transluminal coronary angioplasty (PTCA). NIR stent.
Percutaneous transluminal coronary angioplasty (PT Percutaneous transluminal coronary angioplasty (PTCA). Wallstent.

Bare-metal coronary artery stents are used in PCI for a variety of indications, including stable and unstable angina, acute myocardial infarction (AMI), and multivessel coronary artery disease (CAD). Drug-eluting coronary artery stents have a stent framework with a polymer coating that elutes an antiproliferative drug into the coronary wall for weeks after stent implantation. They were developed to reduce restenosis (ie, recurrent narrowing) rates in stented coronary lesions.

The development of DESs revolutionized coronary intervention to the same degree that balloon angioplasty and bare-metal stents did in the 1980s and 1990s. The first-generation DESs were sirolimus-eluting (Cypher) and paclitaxel-eluting (Taxus) stents. The major clinical endpoint difference between BMSs and first-generation DESs was significantly lower rates of restenosis and target lesion revascularization with DESs.

The goals of further reducing the rate of restenosis and decreasing the frequency of stent thrombosis led to the evolution of second-generation DESs. Those currently used in the United States are either everolimus-eluting (Xience, Promus) or zotarolimus-eluting (Resolute).

DESs have been extensively tested in a wide spectrum of coronary lesions, all of which have demonstrated significant reductions in restenosis and target-lesion revascularization rates in comparison with BMSs or first-generation DESs. The zotarolimus-eluting stent and the everolimus-eluting stent have improved deliverability, thinner struts, and a thinner polymer layer, and they may have clinical advantages over sirolimus-eluting and paclitaxel-eluting stents.[59, 60]

A meta-analysis of 28 randomized, controlled clinical trials involving more than 34,000 patient-years of follow-up indicated that in comparison with BMSs, newer-generation DESs, particularly the everolimus-eluting stent, significantly reduced the risk of target vessel revascularization in patients with ST-segment elevation MI (STEMI) without increasing the risk of adverse safety outcomes, including rates of stent thrombosis.[61]

Currently, DESs have more favorable outcomes than BMSs do, primarily because of significantly lower target vessel revascularization. Therefore, DESs are preferred to BMSs in most PCI settings, including chronic total occlusion (CTO) recanalization, saphenous vein graft (SVG) PCI, bifurcation PCI, aorto-ostial lesions, calcified lesions, PCI in diabetic patients, and PCI in patients with cardiac allograft vasculopathy.

BMSs are recommended for use in patients who have a high bleeding risk, are unable to comply with 1 year of dual antiplatelet therapy, have very large arteries, or are likely to undergo invasive or surgical procedures in the next year.

Although stents are conventionally placed after balloon predilation, a meta-analysis by Piscione et al suggests that in selected coronary lesions, direct stenting may lead to better outcomes.[62] MI rates were lower with direct stenting than with conventional stenting (3.16% vs 4.04%), whereas rates of target vessel revascularization were comparable.

Metallic stents (including both BMSs and DESs) have a low but definite rate of very late adverse events, such as stent thrombosis (0.2-0.6% annually) and restenosis. These late events are partly attributable to the persistence of the polymer and the metallic frame in the vessel. Therefore, the current investigational focus is on developing metallic DESs with bioabsorbable polymers, polymer-free metallic DESs, and bioresorbable scaffolds. Two such stents have been approved by the US Food and Drug Administration and are available for commercial use.

The SYNERGY (Boston Scientific, Marlborough, MA) is an everolimus-eluting platinum chromium stent with an abluminal coating of bioabsobable polymer. This polymer, poly DL-lactide-co-glycolide (PLGA), is mixed with everolimus (the same drug used in the Promus Element DES made by Boston Scientific). In-vivo studies showed that the polymer degradation is essentially complete by 4 months, leaving just the metal stent behind (in contrast to conventional DESs, in which both metal and polymer are permanent). This polymer is believed to play at least a partial role in late stent thrombosis.

The EVOLVE II was a prospective multicenter randomized, controlled, single-blind non-inferiority study (N = 1684) that compared the SYNERGY stent with the Promus Element stent. The primary end point, target lesion failure (TLF), was defined as ischemia-driven revascularization of the target lesion, MI related to the target vessel, or cardiac death at 12 months. The SYNERGY stent was noninferior to the Promus Element stent for TLF (6.7% vs 6.5%; P = .0005) in the intention-to-treat population. There were no significant differences in the secondary end points of stent thrombosis (0.4% vs 0.6%; P = .50), death (1.1% vs 1.1%; P = .95), MI (5.4% vs 5.0%; P = .68) or TLR (2.6% vs 1.7%; P = .50).[63]

The 2-year results presented at the American College of Cardiology’s scientific session in 2016 showed numerically lower definite/probable stent thrombosis with the SYNERGY stent as compared with the Promus Element stent. Long-term data will help determine whether complete degradation of the polymer truly reduces the incidence of very late stent thrombosis.

The Absorb GT1 Bioresorbable Vascular Scaffold (BVS) System (Abbott Vascular, Abbott Park, IL) releases everolimus to limit the growth of scar tissue, but unlike the contemporary metallic stents, it gradually (in ~3 years) dissolves. That is, the scaffold and the polymer are both bioresorbable, leaving behind only the platinum markers at the scaffold edge for fluoroscopic landmarking. The Absorb GT1 is the first BVS stent to receive FDA approval, and it offers a new treatment option for patients who are candidates for PCI but prefer an absorbable device to a permanent metallic stent.

ABSORB III was a multicenter randomized trial of 2008 patients who were randomized to receive either the Absorb or an everolimus-eluting cobalt chromium stent (Xience; Abbott Vascular).[64] At 1 year, the Absorb stent was noninferior for TLF (cardiac death, target vessel MI or ischemia driven target-lesion revascularization). Device thrombosis was more common with the Absorb stent (1.5% vs 0.7%; P = 0.13) and in this study was attributed to a higher rate of in-device postprocedural residual stenosis as a consequence of greater strut thickness or recoil. This is an area of great interest, and future generations will have thinner struts. 


In addition to balloons, stents, and atherectomy devices, other devices, such as thrombus extraction catheters and distal embolic protection devices, play a role in PCI.

In the TAPAS (Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction) trial, thrombus aspiration with an Export catheter before stenting yielded reductions in all-cause mortality (4.7% vs 7.6%) and cardiac death (3.6% vs 6.7%) at 1 year as compared with conventional PCI.[65]

In a pooled analysis of data from three prospective randomized trials, De Vita et al found that although increasing time to treatment was associated with a decreased rate of optimal reperfusion in patients receiving standard PCI, this trend was not seen in patients treated with thrombus aspiration.[66] The investigators concluded that the use of thrombus aspiration limits the adverse effects that prolonged time to treatment has on myocardial reperfusion.

The TASTE (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) trial randomly assigned 7244 STEMI patients to undergo manual thrombus aspiration followed by PCI or to undergo PCI alone.[67] At 30 days, there was no significant difference in all-cause mortality between the thrombus aspiration group (2.8%) and the PCI-only group (3%). At 30 days, the rates of hospitalization for recurrent MI were 0.5% and 0.9% in the two groups, respectively, and the rates of stent thrombosis were 0.2% and 0.5%, respectively.

When followed out to 1 year, the TASTE trial showed that routine thrombus aspiration before PCI in STEMI patients did not significantly reduce the rate of death from any cause or the composite of death from any cause, rehospitalization for MI, or stent thrombosis at 1 year.[68]

In TOTAL (Trial of Routine Aspiration Thrombectomy with PCI versus PCI Alone in Patients with STEMI), the largest trial on routine thrombus aspiration, 10,732 patients with STEMI were randomly assigned to upfront manual aspiration thrombectomy or PCI alone.[69] There were no differences between the two groups with respect to cardiovascular death, recurrent MI, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The rates of stent thrombosis or target-vessel revascularization were also similar.

As suggested in a previous meta-analysis, the thrombectomy group had a higher incidence of stroke within 30 days: 0.7% in the thrombectomy group versus 0.3% in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13-3.75; P = .02).[69] Interestingly, there was a continued increase in strokes even at 30 days and 180 days in the thrombectomy group, which could not be easily explained and could also be a matter of chance. The subgroup analysis showed no benefit in heavy thrombus burden, TIMI 0-1 flow, or anterior infarcts.

A meta-analysis of these three thrombectomy trials showed no benefit of routine aspiration thrombectomy with respect to death, reinfarction, or stent thrombosis. There was small but nonsignificant increase in stroke with thrombectomy.[70]

In the 2016 update of STEMI guidelines from ACC/AHA/SCAI, routine aspiration thrombectomy was no longer recommended before primary PCI. The level of recommendation was changed from class IIa to class III. Because of insufficient data, “bailout” thrombectomy was a class IIb recommendation.[71]

Distal embolic protection devices

PCI in a saphenous vein graft (SVG) is considered a high-risk procedure, given the increased incidence of distal embolization and no-reflow phenomenon. The SAFER (Saphenous Vein Graft Angioplasty Free of Emboli Randomized) trial initially proved the benefit of embolic protection devices (EPDs) in reducing the 30-day incidence of MACE (9.6% vs 16.5%), MI (8.6% vs 14.7%), and no-reflow (3% vs 9%).[56]

Although the ACC/AHA guidelines gave EPDs in SVGs a class I recommendation, EPD use remains low, for a variety of reasons (eg, anatomic challenges, cumbersome devices, increased complications, and emergence of alternate techniques such as direct stenting, mesh stents, undersizing stents with higher stent-to-lesion length ratio) and laser atherectomy.

Observational data from the NCDR Cath Registry on 49,325 patients who underwent SVG intervention reported low EPD use (~21%) and no reduction in adverse events after 3 years of follow-up. In fact, in the EPD group, there were higher procedural complications of no-reflow, dissection, perforation, and periprocedural MI. 

One of the conclusions that can be inferred from the available data is that not all SVG interventions are the same. The decision to use EPDs should be based on thrombus/plaque burden, risk of embolization, anatomic complexity, and operator familiarity with the devices.[72]

There is no indication for EPD use in native coronary arteries. A 15-month follow-up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) trial found that in primary PCI for STEMI, routine use of distal protection increased the incidence of stent thrombosis and clinically driven target lesion/vessel revascularization.[73]

Vascular closure devices

For transfemoral catheterizations, hemostasis can be achieved either by manual compression or by use of vascular closure devices. The results of four meta-analyses suggested that vascular closure devices do not decrease vascular complications, bleeding complications, or the need for blood transfusions, whereas they do decrease time to hemostasis and time to ambulation.[74, 75, 76, 77]

For transradial catheterizations, hemostasis is generally achieved with manual compression using transradial bands and patent hemostasis technique.

Patient Preparation

PCI is performed on an elective as well as an urgent or emergency basis. Elective patients present to the hospital on the morning of the procedure at a scheduled time. A history is obtained and a physical examination performed. Basic blood tests (including a complete blood count [CBC], basic metabolic profile [BMP], and coagulation profile) and electrocardiography (ECG) are performed. Informed consent is obtained.

A full dose of aspirin (325 mg) is given on the day of procedure. If patients have had prior allergic reactions to contrast, prednisone is generally given for at least three doses beforehand. Some laboratories also use Benadryl, a histamine H1 blocker, or both. Patients with food allergies and asthma are also occasionally premedicated with steroids. Coronary angiography is performed with full sterile technique. Preprocedural antibiotic prophylaxis is not recommended.

Anesthesia and positioning

The patient is placed in the supine position, prepared and draped in a standard sterile fashion. The procedure is performed with the patient under conscious sedation (in most instances, using midazolam and fentanyl).

Safe access is extremely important for the success of PCI, and therefore, special attention is paid to the technique. Lidocaine 2% is used as the local anesthetic agent.


In patients undergoing coronary angiography or PCI, the use of sliding-scale hydration guided by left ventricular end-diastolic pressure (LVEDP) reduces not only the risk of contrast nephropathy but also the risk of clinical events at 6 months.[78]

In the POSEIDON (Prevention of Contrast Renal Injury with Different Hydration Strategies) trial, patients treated with the LVEDP-guided hydration and conventional-hydration strategies were given 3 mL/kg of 0.9% saline over the course of an hour before the procedure.[78] During the procedure, patients in the standard arm received 1.5 mL/kg/hr, whereas patients in the LVEDP-guided arm received 5 mL/kg/hr if the LVEDP was below 13 mm Hg, 3 mL/kg/hr if the LVEDP was 13-18 mm Hg, and 1.5 mL/kg/hr if the LVEDP was above 18 mm Hg.

The use of sliding-scale hydration reduced the primary endpoint (defined as a 25% or 0.5-mg/dL increase in serum creatinine levels) by 59%.[78] At 6-months’ follow-up, LVEDP-guided treatment significantly reduced the composite endpoint of death, MI, and dialysis by 68%.

On the basis of several studies, the most widely recommended hydration regimen is isotonic crystalloid (1.0-1.5 mL/kg/hr) for 3-12 hours before the procedure and 6-24 hours after the procedure.

Earlier studies on N-acetyl-L-cysteine produced conflicting results; however, ACT (Acetylcysteine for Contrast-Induced Nephropathy Trial) study data on 2308 randomly assigned patients demonstrated no benefit with respect to reducing the incidence of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients.[79]




Coronary angiography and percutaneous coronary intervention (PCI) are more commonly performed via the femoral or the radial artery and less commonly performed via the brachial or ulnar artery. Overall, the femoral artery is the most common route of access for these procedures in the United States; however, the use of radial access is increasing. In selected labs in the United States and in some parts of Europe, radial artery access exceeds 90%.  

Two randomized, controlled trials reported equal or better outcomes with transradial access than with femoral access in ST-segment elevation myocardial infarction (STEMI) patients undergoing PCI. In the RIFLE STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study, a multicenter randomized trial involving 1001 STEMI patients, radial access was associated with significantly lower rates of cardiac mortality (5.2% vs 9.2%) and bleeding (7.8% vs 12.2%) than femoral access was.[80]

The RIVAL (Radial Versus Femoral Access for Coronary Intervention) trial compared the efficacy and bleeding outcomes of radial and femoral access separately in patients with STEMI and non-STEMI (NSTEMI).[81] Radial access was associated with reduced all-cause mortality (1.3% vs 3.2%) and reduced death/myocardial infarction (MI)/stroke (2.7% vs 4.6%) in STEMI patients but not in NSTEMI patients. In both STEMI and NSTEMI groups, radial access was associated with significantly reduced ACUITY major bleeding and major vascular access site complications.

The MATRIX trial compared outcomes of radial access with those of femoral access in 8404 patients with acute coronary syndrome.[82] The radial group had lower all-cause mortality as well as Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass grafting (CABG).

The European Society of Cardiology (ESC) guidelines on STEMI patients recommend preference of radial over femoral access, if it is performed by an experienced radial operator (class IIa, level B). The Society for Cardiovascular Angiography and Interventions released a consensus statement on best practices for the use of radial access for diagnosing and treating coronary artery disease (CAD), focusing on avoiding radial artery occlusion, reducing radiation exposure, and using the transradial approach in STEMI.[83]

Recommendations for STEMI patients include the following:

  • Before integrating the radial approach into practice, clinicians should gain experience with at least 100 elective radial procedures and have a femoral crossover rate lower than 4%
  • Practitioners should start with easier cases and ensure that all laboratory personnel are comfortable with the procedure
  • A bailout approach to either contralateral radial or femoral access should be prepared in advance


The patient is prepared as described earlier (see Patient Preparation).

For transradial catheterization, an arteriotomy is made approximately 2 cm proximal to the radial styloid process so as to avoid the distal bifurcation and diminutive vessels. While palpation is being done, the radial artery is punctured with a micropuncture needle, and a hydrophilic sheath is placed by means of the modified Seldinger technique.

Once the sheath is in place, an intra-arterial vasodilator is given (nicardipine 500 µg or verapamil 5 mg), with half the dose administered at the beginning of the procedure and the other half at the end. Intravenous (IV) heparin dramatically reduces the risk of radial artery occlusion and is therefore often used in transradial catheterization (usual dose, 50 units/kg; maximum total dose, 5000 units).

For transfemoral catheterization, the arteriotomy site is the common femoral artery, above its bifurcation into the deep femoral artery (profunda femoris) and the superficial femoral artery and below the inferior epigastric artery. Because the skin crease can sometimes be misleading, a combination of various other anatomic landmarks may be used, such as bony landmarks (aiming 2 cm below the center of the inguinal ligament) and the point of maximal palpable impulse.

Fluoroscopy is often used to mark the femoral head, and the target zone for the arteriotomy is the middle of the femoral head. A micropuncture (21-gauge) or 18-gauge needle is used to puncture the femoral artery, and a sheath is placed with the modified Seldinger technique. Sheath size varies according to the preference of the operator; in general, it is in the range of 4-6 French.

Once access is obtained, catheters are advanced over a 0.035-in. J-tip guide wire into the ascending aorta. Various different catheter shapes are available; the choice depends on the operator’s preference and the patient’s anatomy. Selective coronary angiography is performed in different views (at least two orthogonal views for each segment of the coronary) using hand or power injections of iohexol.

Guide catheters have the same external diameter as diagnostic catheters but a larger lumen and are used for PCI. Once the catheter has engaged the coronary ostium and diagnostic angiograms have been obtained, weight-based IV anticoagulant (unfractionated heparin [UFH], bivalirudin, or low-molecular-weight heparin [LMWH]) therapy may be administered. If the patient is not on long-term dual antiplatelet therapy (DAPT), a loading dose of a P2Y12 inhibitor is also given. As noted above, all patients should have been pretreated with aspirin.

A 0.014-in. guide wire is then advanced into the coronary artery across the stenotic lesion. All balloon catheters and other devices will be tracked over this wire. In some cases, direct stenting of the lesion can be done; however, in most cases, vessel preparation with either predilation with a semicompliant balloon or an atherectomy device is performed. The balloon is then withdrawn, and a stent of appropriate length and diameter is advanced over the coronary guide wire, positioned across the lesion, and deployed.

Depending on the angiographic appearance of the stent, postdilation of the stent may or may not be performed with a noncompliant balloon. An intravascular imaging tool, such as intravascular ultrasonography (IVUS) or optical coherence tomography (OCT) (see Anatomic and Physiologic Assessment), can be used for further delineation and assessment of the anatomy including plaque burden, vessel size, and stent deployment.

After the PCI result is deemed adequate, the coronary wire is removed and final angiograms are taken.

Access sheath removal

In transradial catheterization, the sheath is removed immediately after the procedure, and a compression band is applied to the wrist. With a goal of patent hemostasis, this band is left inflated for 90-120 minutes and then gradually deflated.

In transfemoral catheterization, hemostasis is achieved either by the use of vascular closure devices (inserted at the end of the case) or by manual compression (a few hours later when activated clotting time [ACT] is in the appropriate range).

Anatomic and Physiologic Assessment

Intravascular ultrasonography

Although coronary angiography provides a display of luminal narrowing in multiple planes and is useful in guiding PCI, it provides only limited information about the vessel wall, which is where the atherosclerotic process resides.

IVUS (see the image below) was developed to provide information about the plaque, the vessel wall, and the degree of luminal narrowing. It provides a tomographic cross-section of the vessel, allowing operators to gather significant qualitative and quantitative information that is potentially valuable for assessing stenosis severity and determining the true extent of atherosclerotic involvement.

Example of intravascular ultrasonography (IVUS) im Example of intravascular ultrasonography (IVUS) image in percutaneous transluminal coronary angioplasty (PTCA).

The lumen border and the media-adventitia interface are the key landmarks that should be identified during interrogation. Plaque can be distinguished from the lumen on the basis of differences in echogenicity. In addition to providing information about the amount and distribution of plaque, IVUS can identify features of plaque composition (eg, calcification and lipid collections) that may not be appreciated by angiography alone.

Frequent uses of IVUS include assessment of indeterminate lesions and evaluation of adequate stent deployment. The latter is particularly important, in that proper deployment of drug-eluting stents (DESs) is critical for reducing thrombosis rates. Development of other technologies (eg, OCT and plaque thermography) have enhanced our ability to interrogate coronary arteries.

Optical coherence tomography

OCT uses light-based imaging to capture micrometer-resolution images of the artery wall. It has 10 times higher resolution than IVUS does but is unable to penetrate as deep into the vessel wall. OCT’s high resolution enables it to better evaluate stent strut apposition and neointimal stent strut coverage.

Coronary physiologic assessment

Intracoronary Doppler pressure wires are used to characterize coronary lesion physiology and estimate lesion hemodynamic severity. Comparison of the pressure distal to a lesion with aortic pressure at maximal coronary hyperemia enables determination of fractional flow reserve (FFR) (see the image below).

Fractional flow ratio (FFR). Pressure wire is adva Fractional flow ratio (FFR). Pressure wire is advanced across left anterior descending (LAD) artery stenosis, and intracoronary adenosine is given. FFR ratio is recorded at baseline and then after adenosine push is given. Here, LAD lesion and FFR post adenosine are shown.

An FFR measurement lower than 0.80 during maximal hyperemia (induced via administration of adenosine) is consistent with a hemodynamically significant lesion. This determination is useful in deciding whether to perform PCI in an angiographic intermediate lesion. Clinical data—namely, the findings from the DEFER (Deferral of Percutaneous Coronary Intervention) study—support using this approach; a low event rate was seen in medically managed patients with angina and an FFR measurement greater than 0.75.

The FAME (Fractional Flow Reserve versus Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease) trial showed that routine measurement of FFR during angioplasty reduced the risk of death, MI, or repeat revascularization by 30% and the risk of death or MI by 35%, compared with the current practice of using angiography to guide stenting decisions.[84]

In this study, a cutoff FFR value of 0.80 was used to define a nonischemic lesion. A 2-year follow-up of the FAME trial showed continuing significant reductions in the combined endpoint of death and MI with the use of FFR in comparison with standard angiography-guided PCI.[85]

The FAME 2 trial randomly assigned patients with stable CAD who had at least one stenosis with an FFR less than 0.8 to receive either FFR-guided PCI plus optimal medical therapy or optimal medical therapy alone.[86] The occurrence of the primary endpoint—a composite of any-cause mortality, nonfatal MI, or urgent revascularization within 2 years—was significantly lower in the PCI group than in the medical therapy group (8.1% vs 19.5%).

However, it is important to note that this difference in primary endpoint was primarily driven by a reduction in the rate of urgent revascularization in the PCI group (4% vs 16.3); there were no significant between-group differences in mortality and MI rate.[86]

The FAME 3 study, currently under way, is a multinational multicenter trial designed to compare FFR-guided PCI (using second-generation DESs) with coronary artery bypass grafting (CABG) in patients with multivessel CAD.

Currently, the use of FFR is recommended to assess the hemodynamic significance of angiographically intermediate (40-70%) stenosis. Both FFR and IVUS have shown favorable outcomes when used to assess angiographically intermediate lesions; however, the data on FFR are more robust.

A meta-analysis by Johnson et al indicated that FFR values should be viewed not only in the context of a cut point used in deciding whether to revascularize patients through PCI but also as part of a spectrum of values indicating which patients will receive the most benefit from PCI.[87]

The analysis, which utilized data from FFR trials (9173 lesions) and patient-level data (6961 lesions), supported the use of the 0.75-0.80 range, the same range employed in major FFR studies, as the optimal cut point for PCI; however, the results also indicated that the further beneath that range a patient’s FFR falls, the more benefit the patient will receive from PCI.[87] Johnson et al also found evidence that measuring the FFR after PCI can aid in determining a patient’s prognosis, with higher post-PCI numbers being associated with lower subsequent event rates.

Adjunctive Therapies in Catheterization Laboratory

Antithrombotic therapy

Aspirin and heparin have been the traditional adjunctive medical therapies for patients undergoing coronary angioplasty and have been shown to decrease complications after the procedure. Since 1994, several antithrombotic drugs have been developed that have advantages over standard heparin. Although heparin is an effective anticoagulant, it has several limitations, including variable pharmacokinetics requiring careful monitoring, inhibition by substances released from activated platelets, and inability to inhibit fibrin-bound thrombin.

To address these limitations, several direct thrombin inhibitors have been developed. Hirudin and bivalirudin were evaluated in multicenter trials,[22, 88, 89, 90] and both agents were found to be slightly better than heparin in preventing ischemic complications during balloon angioplasty, though they had no effect on restenosis rates.

At some centers, LMWHs are being substituted for standard heparin in the treatment of patients with acute coronary syndrome (ACS) and during coronary interventions. Factor IX and factor Xa inhibitors are being evaluated as potential alternative anticoagulants; however, trials have failed to show a significant difference in efficacy of factor Xa inhibition between these agents and UFH.

In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial,[91] 3602 patients presenting with STEMI and undergoing PCI were treated with bivalirudin and had substantially lower 30-day rates of major hemorrhagic complications and lower rates of net adverse clinical events (ie, major bleeding or composite major adverse cardiovascular events [death, reinfarction, target-vessel revascularization for ischemia, or stroke]) than patients treated with heparin plus a glycoprotein (GP) IIb/IIIa inhibitor.

The investigators continued to follow patients for 1 year.[91] Data were available for 1696 patients in the bivalirudin group and 1702 patients in the heparin plus GPIIb/IIIa inhibitor group. At 1 year, the bivalirudin group continued to have reduced rates for major bleeding and adverse events as compared with the heparin plus GPIIb/IIIa inhibitor group. Death, reinfarction, target-vessel revascularization for ischemia, and stroke rates were similar in the two groups.

The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial,[92] which studied the impact of age on outcomes in moderate- and high-risk non–ST-segment elevation ACS (NSTE-ACS), found that patients aged 75 years or older who were treated with bivalirudin alone had similar ischemic outcomes but significantly lower bleeding rates than those who were treated with heparin plus GPIIb/IIIa inhibitors, both overall and in the PCI subset.

In this trial, outcomes were analyzed at 30 days and at 1 year in four age groups, overall, and in those undergoing PCI.[92] Of the 13,819 patients studied, 3655 (26.4%) were younger than 55 years, 3940 (28.5%) were aged 55-64 years, 3783 (27.4%) were aged 65-74 years, and 2441 (17.7%) were aged 75 years or older. Older patients had more cardiovascular risk factors and had a higher acuity at presentation.

In the NAPLES (Novel Approaches for Preventing or Limiting Events) trial, Tavano et al compared bivalirudin with UFH plus a GPIIb/IIIa inhibitor (ie, tirofiban) during PCI in 335 patients with diabetes mellitus and concluded that elective PCI with bivalirudin monotherapy is safe and feasible in patients with diabetes.[93]

The bivalirudin group experienced significantly less in-hospital bleeding (8.4% vs 20.8%).[93] Non–Q-wave MI rates were similar in the two groups (10.2% for bivalirudin vs 12.5% for UFH-tirofiban. In the early days of stenting, multiple antiplatelet agents and warfarin were used in an attempt to prevent stent thrombosis, but thrombosis continued to occur in approximately 6% of patients.

The EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial randomly assigned 2218 STEMI patients to receive either bivalirudin or UFH or LMWH with optional GP IIb/IIIa inhibitors.[94] The bivalirudin group had a lower risk of the primary outcome, which was a composite of death or major bleeding not associated with CABG (5.1% vs 8.5%). It also had a lower rate of the principal secondary outcome, a composite of death, reinfarction, or non-CABG major bleeding (6.6% vs 9.2%).

These differences reported in the EUROMAX trial were primarily driven by a reduced risk of major bleeding (2.6% vs 6%); there were no significant differences in the rates of death or reinfarction.[94] The bivalirudin group had higher rates of acute stent thrombosis (1.1% vs 0.2%).

The single-center HEAT PPCI (How Effective Are Antithrombotic Therapies in Primary PCI) trial randomly assigned 1812 STEMI patients to receive either bivalirudin or UFH and compared the two regimens with respect to primary efficacy outcome (composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target-lesion revascularization) and primary safety outcome (incidence of major bleeding).[95]

In this trial, heparin reduced the incidence of major adverse ischemic events as compared with bivalirudin (5.7% for heparin vs 8.7% for bivalirudin).[95] There was no increase in the rate of bleeding complications with heparin (3.5% vs 3.1% for bivalirudin).The results of the HEAT PPCI trial differed from those of previous trials and suggested that bleeding risk is not increased with heparin.

In concordance with the HEAT PPCI results were the results of the large MATRIX trial, which randomly assigned 7213 acute coronary syndrome patients undergoing PCI to receive either bivalrudin or UFH.[96] There was no significant difference in major adverse cardiovascular events (MACE; 10.3% vs 10.9%; relative risk [RR], 0.94; 95% confidence interval [CI], 0.81-1.09; P = 0.44) or net adverse clinical events (11.2% vs 12.4%; RR, 0.89; 95% CI, 0.78-1.03; P = 0.12).

Post-PCI bivalrudin infusion was given to a subgroup of patients but did not show significantly lower urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events compared to patients who did not receive the post-PCI infusion.[96]

In summary, the early trials showed better outcomes with reduced bleeding in patients who received bivalrudin, but the two subsequent trials, HEAT PPCI and MATRIX, showed no such benefit. Heparin is significantly cheaper than bivalrudin, and the equivocal results in the more recent trials have led to another change in practice patterns, whereby bivalrudin use in PCI has decreased.

Antiplatelet therapy

The most feared complication of intracoronary stents has been thrombotic occlusion of a freshly deployed metallic endoprosthesis. Aggressive antiplatelet therapy has been shown to significantly reduce the risk of stent thrombosis and is required in all patients receiving a stent.

Patients receiving stents are now treated with a combination of aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, ticagrelor, or cangrelor); with this DAPT, the development of less thrombogenic stents and improvements in stent deployment technology, the incidence of subacute thrombosis currently is less than 1%.

Today, DAPT is provided to all stent patients for a minimum of 4 weeks after a bare-metal stent (BMS) is placed and for a minimum of 6-12 months when a DES is used. Several trials have suggested that a shorter duration of P2Y12 inhibitor administration may be safe in patients with second-generation DESs, but the guidelines still recommend 12 months of DAPT in patients who present with acute coronary syndrome.

For patients who undergo PCI for stable ischemic heart disease (SIHD), the American College of Cardiology (ACC) and the American Heart Association (AHA) now recommend a shorter duration of DAPT.[97] Patients who receive DESs for SIHD should receive DAPT (with clopidogrel) for 6 months (class I recommendation). If such a patient is at high risk for severe bleeding (eg, is undergoing major intracranial surgery) or develops a high risk of bleeding (eg, needs treatment with oral anticoagulation), the P2Y12 inhibitor could be discontinued at 3 months after stent implantation (class II b recommendation).

Issues remain as to whether the duration of aspirin and P2Y12 inhibitor therapy should be longer in patients who received first-generation DESs. In the authors’ view, treatment with 81 mg of aspirin should be maintained for life in all DES patients, and lifetime P2Y12 inhibitor therapy should be considered unless bleeding contraindications restrict its use. Currently, there are multiple ongoing studies designed to evaluate the question of optimal DAPT duration for second-generation DESs.

Although pretreatment with P2Y12 inhibitors has been recommended by the guidelines for years, there has been no evidence supporting this strategy. The ACCOAST (Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention or as Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction) study was very important, in that it was the first, and to date the only, randomized controlled trial to have examined a pretreatment strategy.[98]  The results, surprisingly to many, showed that pretreatment had no benefit in terms of MACE and was associated with an increase in bleeding.

The ACCOAST study compared pretreatment with prasugrel 30 mg and a further 30 mg dose before PCI with a regimen of prasugrel 60 mg after diagnostic angiography but before PCI among 4033 patients with NSTEMI who were scheduled for an early invasive strategy.[98] The median duration of pretreatment was 4.3 hours. Of the 4033 patients, 69% underwent PCI, 6% required surgical revascularization, and the remainder were treated conservatively.

At 7 days, patients randomized to the pretreatment arm experienced no reduction (hazard ratio [HR], 1.02; 95% CI, 0.84-1.25; P = 0.81) in the primary end point (ie, cardiovascular death, recurrent MI, stroke, urgent revascularization, and bailout use of GPIIb/IIIa inhibitors), and no benefits emerged at 30 days.[98] TIMI major bleeds were significantly increased in the pretreatment group at 7 days (2.6% for pretreatment vs 1.4% for no pretreatment; HR, 1.90; 95% CI, 1.19-3.02; P = 0.006). 

As the 2015 ESC guidelines stated,[99] "Initiation of P2Y12 inhibitors soon after the diagnosis of NSTE-ACS irrespective of management strategy has been recommended. This implies pretreatment, defined as P2Y12 inhibitor administration before coronary angiography, in patients scheduled for an invasive approach.... As the optimal timing of ticagrelor or clopidogrel administration in NSTE-ACS patients scheduled for an invasive strategy has not been adequately investigated, no recommendation for or against pretreatment with these agents can be formulated.”

Concerns still exist regarding the risk of bleeding and platelet transfusion requirements in patients taking a P2Y12 inhibitor who require urgent CABG. Because emergency CABG is rare, there may be time to risk-stratify patients and to give a P2Y12 inhibitor before cardiac catheterization. If CABG is required, the effect of a P2Y12 inhibitor usually diminishes within 5 days.

Another important consideration is the clopidogrel loading dose. ACC/AHA guidelines recommend giving 600 mg within the 6 hours preceding PCI with stenting.[3]

Results of the HORIZONS-AMI study also indicated that a 600-mg loading dose of clopidogrel yielded better clinical outcomes than a 300-mg dose.[100] The 2158 patients in the 600-mg group had significantly lower unadjusted 30-day mortality than the 1153 in the 300-mg group (1.9% vs 3.1%), as well as lower rates of reinfarction (1.3% vs 2.3%) and stent thrombosis (1.7% vs 2.8%). Bleeding rates did not differ. Similar differences were shown in patients who received either bivalirudin or UFH plus a GP inhibitor.

The GRAVITAS (Gauging Responsiveness with A VerifyNow Assay—Impact on Thrombosis And Safety) study, which enrolled 2214 patients with high on-treatment reactivity 12-24 hours after PCI, found that high-dose clopidogrel (600 mg initially, 150 mg/day thereafter) provided a 22% absolute reduction in the rate of high on-treatment reactivity at 30 days in comparison with standard treatment (no additional loading dose, 75 mg/day).[101]

However, the GRAVITAS investigators noted no difference in the primary endpoint of 6-month incidence of death from cardiovascular causes, nonfatal MI, or stent thrombosis.[101] Severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition was lower in the standard group, but the decrease did not reach statistical significance.

Use of newer intravenous (IV) antiplatelet agents such as cangrelor may help overcome these issues. In June 2015, cangrelor was approved by the US Food and Drug Administration (FDA) for use in adults undergoing PCI. Aspirin 325 mg should be given before all PCIs and then maintained at a dosage of 81 mg/day.

Clopidogrel is the most frequently utilized P2Y12 inhibitor. Numerous studies have shown the inconsistency in the metabolism of this drug as a result of variations in the CYP2C19 pathway. Clopidogrel is a prodrug that is metabolized to an active form by the cytochrome (CYP) 450 enzyme system in the liver. Research has demonstrated that genetic variation at the CYP450 2C19 locus results in decreased metabolic activation of clopidogrel and increased risk of stent thrombosis and ischemic events. Patients with two or three abnormal alleles in their CYP2C19 genotype are at higher risk for MACE when treated with clopidogrel.[102]

This finding led to an update to the package insert for clopidogrel, which now includes a “black box” warning for use in patients who are “poor metabolizers” (ie, those who have two abnormal alleles at the CYP 2C19 locus; approximately 2-4% of white patients fall into this category).

Individuals with a single abnormal allele have intermediate metabolism of clopidogrel to the active metabolite. In a meta-analysis of nine studies and almost 10,000 patients, Mega et al found that the presence of even one reduced-function CYP2C19 allele in patients treated with clopidogrel after PCI was associated with a significantly increased risk of MACE, particularly stent thrombosis.[103]  

Studies of platelet function testing have shown variability in the pharmacodynamic response to clopidogrel, and studies of genetic testing have identified genetic polymorphisms that affect its absorption (ABCB1), metabolism (eg, CYP2C19) and ultimately its pharmacodynamic effects. Genetic testing for CYP2C19 polymorphisms has potentially important prognostic implications.

In population-based studies, patients with high on-treatment platelet reactivity have had an increased risk of MACE. Unfortunately, studies have not shown that measuring platelet reactivity in an individual patient (primarily with the VerifyNow assay) is useful for identifying those at risk. Currently, measurement of platelet reactivity is still reserved for use as a research tool.[104, 105]

Besides genetic polymorphisms, there are clinical factors to consider, such as obesity and diabetes mellitus, as well as potential drug interactions, such as those with calcium-channel blockers and proton pump inhibitors (PPIs). In particular, omeprazole was implicated in clopidogrel hyporesponsiveness. However, the COGENT trial demonstrated that there was no increase in MACE in patients who took clopidogrel plus a PPI as compared with clopidogrel alone.[106]

Prasugrel is a thienopyridine adenosine diphosphate (ADP) receptor inhibitor that inhibits platelet aggregation. It has been shown to reduce new and recurrent MIs.[107] The loading dose is 60 mg orally given once, and the maintenance dosage is 10 mg/day orally (given with aspirin 75-325 mg/day).

Prasugrel is indicated for reducing thrombotic cardiovascular events (including stent thrombosis) in patients with an ACS that is managed with PCI. It is used specifically for unstable angina or NSTEMI or for acute STEMI that is managed with primary or delayed PCI.

TRITON TIMI (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel—Thrombolysis in Myocardial Infarction) 38 analyzed whether the type, size, and timing of MI affected prasugrel’s ability to reduce new or recurrent MI.[107] Compared with clopidogrel, prasugrel significantly reduced the overall risk of any type of MI (eg, procedure-related, nonprocedural, and consistently across MI size). Significant, sometimes fatal, bleeding occurred more often with prasugrel than with clopidogrel.

Ticagrelor, a cyclopentyl-triazolo-pyrimidine, is an oral P2Y12 receptor antagonist that reversibly inhibits platelets. It does not require hepatic bioactivation, because it is an active drug. The PLATO (Platelet Inhibition and Patient Outcomes) trial, looking at 18,264 patients with ACS (35% STEMI), showed that ticagrelor reduced the composite primary efficacy event (death, MI, or stroke) in comparison with clopidogrel (9.8% vs 11.7%) but increased non–CABG-related major bleeding (2.8% vs 2.2%) and fatal intracranial hemorrhage.[108]

Potential disadvantages of ticagrelor include side effects such as dyspnea, ventricular pauses, significantly greater cost than generic clopidogrel, and increased concentration of uric acid and creatinine.

On the basis of the benefit observed in these trials, current NSTE-ACS guidelines state that it is reasonable to use ticagrelor in preference to clopidogrel for DAPT in patients with NSTE-ACS who undergo an early invasive or ischemia-guided strategy. Prasugrel (at the time of PCI) may be chosen over clopidogrel for DAPT in patients with NSTE-ACS who undergo PCI and are not at high risk for bleeding complications.

In mid-2015, the FDA approved the IV antiplatelet drug cangrelor. It is indicated as an adjunct to PCI to reduce stent thrombosis, periprocedural MI, and repeat coronary revascularization in patients who were not treated with an oral P2Y12 inhibitor for any reason (eg, vomiting or intubation). It is a direct-acting P2Y12 platelet receptor inhibitor that blocks ADP-induced platelet activation and aggregation. It is rapidly distributed and metabolized and reaches Cmax in 2 minutes of infusion. Its effect rapidly clears once the infusion is stopped, and platelet function returns to normal in 60 minutes.

An oral P2Y12 platelet inhibitor should be administered in order to maintain platelet inhibition after discontinuance of the cangrelor infusion. Whereas ticagrelor 180 mg could be initiated at any time during the cangrelor infusion, prasugrel 60 mg and clopidogrel 600 mg should only be given immediately after discontinuance of cangrelor. 

Glycoprotein inhibitor therapy

PCI results in disruption of the coronary endothelium, which leads to platelet activation. Activated platelets bind to the vessel wall (adhesion) and to each other (aggregation) and release numerous vasoactive compounds.

Aspirin blocks the cyclooxygenase pathway and reduces thrombotic complications after balloon angioplasty. However, despite heparin and aspirin therapy, thrombotic complications are not eliminated. Studies identified the importance of the GPIIb/IIIa receptor, which binds fibrinogen and mediates platelet cross-linking and aggregation. The introduction of GP IIb/IIIa inhibitors had a major influence on PCI treatment strategies in the 1990s, but these drugs are now used much less frequently than they once were.

Early studies of GPIIb/IIIa inhibitors showed the following:

  • Abciximab, tirofiban, and eptifibatide are capable of reducing ischemic complications in patients undergoing balloon angioplasty and coronary stenting
  • In primary PCI, GPIIb/IIIa inhibitors can improve flow and perfusion and reduce adverse events
  • Abciximab may improve outcomes in patients when given before arrival in the catheterization laboratory for primary PCI [109]
  • A meta-analysis of GPIIb/IIIa inhibitor trials showed a significant reduction in early mortality when these agents are used during coronary intervention; the combined endpoint of death or MI was also reduced significantly at 30 days
  • The EVA-AMI (Eptifibatide vs Abciximab in Primary PCI for Acute ST Elevation Myocardial Infarction) trial, which compared the efficacy of two GPIIb/IIIa inhibitors as adjuncts to PCI in 427 patients with STEMI, showed that double-bolus eptifibatide followed by a 24-hour infusion was as effective as single-bolus abciximab followed by a 12-hour infusion for ST-segment resolution [110]
  • These agents are effective at reducing ischemic complications of PCI; however, they have not been shown to improve outcome in saphenous vein graft PCI
  • A meta-analysis of 22 studies including 10,123 patients evaluated the use of GPIIb/IIIa inhibitors during elective PCI in patients pretreated with clopidogrel determined that GPIIb/IIIa inhibitors had no effect on mortality or major bleeding but were associated with a decrease in the incidence of nonfatal MI and an increase in the rate of minor bleeding [111]

The evidence supporting the use of GPIIb/IIIa inhibitors derives largely from the time before the widespread use of oral P2Y12 inhibitors. Several studies failed to show a benefit with upstream administration of GPIIb/IIIa inhibitors. In view of these findings, coupled with the increased risk of bleeding, routine use of these agents is no longer recommended. GPIIb/IIIa inhibitors may be used as an adjunctive therapy at the time of PCI, on an individual basis, for large thrombus burden or inadequate P2Y12 receptor antagonist loading.


The common complications of PCI are bleeding, hematoma, and pseudoaneurysm at the access site. To minimize the risk of these complications, extreme care must be taken in obtaining access at the beginning of the procedure.

Bleeding avoidance strategies (eg, bivalirudin and the radial approach) appear to lower the risk of post-PCI bleeding for both men and women; however, such strategies may be of particular significance in female patients, in that the absolute differences in risk are substantially greater in women.[112]

A retrospective cohort analysis of data on 2,820,874 PCI procedures from the CathPCI registry demonstrated that the use of radial access for PCI (r-PCI) was on the increase and that the procedure was associated with a lower risk of bleeding and vascular complications than traditional transfemoral PCI, even after age, sex, and clinical presentation were accounted for.[113]

Anaphylaxis caused by the contrast agent can occur; therefore, a careful preprocedural history must be obtained. Patients with a prior anaphylactoid reaction to the contrast media should receive appropriate steroid prophylaxis before repeat contrast administration. Contrast administration is one of the leading causes of hospital-acquired acute kidney injury (AKI). The only strategies that have been shown to minimize the risk of AKI are hydration and minimizing the use of contrast.

Early registries of balloon angioplasty results showed complication rates that were much higher than those typically observed today. Reductions in the complication rate have been complemented by improvements in the acute success rate. Previously, registries such as the National Heart, Lung, and Blood Institute (NHLBI) Coronary Angioplasty Registry reported primary success rates of 61%. Today, with the use of stents and adjunctive pharmacotherapy, success rates range from 95% to 99%.

The mechanism by which balloon angioplasty or stenting improves luminal diameter is associated with significant local trauma to the vessel wall, which can, in turn, lead to occlusive complications in a minority of patients. Coronary artery dissection typically results from the vessel injury secondary to balloon expansion. Animal and postmortem human studies have shown that localized dissection at the site of balloon expansion is detected angiographically in as many as 50% of patients immediately after balloon angioplasty.

Such small dissections probably are necessary to obtain adequate lumen expansion; they rarely interfere with antegrade blood flow and are usually unimportant. Angiographic follow-up typically shows no residual evidence of a dissection as early as 6 weeks after angioplasty in most of the cases studied. However, larger dissections can lead to complications.

Often, these dissections are treated with a stent to cover the dissection flap. Coronary perforation or rupture is very rare (occurring in fewer than 1% of cases) and is typically associated with the use of ablative devices or oversized balloons. It can occur from the wire tip or at the culprit lesion. Wire perforations are typically small and usually do not warrant further intervention; perforations from balloon inflation or stent implantation can occasionally necessitate treatment with a covered stent graft.

Abrupt vessel closure may occur in as many as 5% of balloon angioplasty cases, usually developing when the true lumen is compressed by a large dissection flap, thrombus formation, superimposed coronary vasospasm, or a combination of these processes. The presence of large coronary dissections immediately after balloon angioplasty is associated with a fivefold increase in the risk of abrupt closure.

Since the introduction and implementation of intracoronary stents and newer antiplatelet drugs, the incidence of abrupt closure has decreased significantly, to less than 1%. Microembolization of plaque debris or adherent thrombus may also cause acute complications during angioplasty and may contribute to postprocedural cardiac enzyme elevation and chest pain in some patients.

In fewer than 1% of angioplasty patients, microembolization of the platelet-rich thrombus may cause diffuse distal arteriolar vasospasm secondary to release of vasoactive agents, resulting in no-reflow. This complication is difficult to treat but may respond to intracoronary calcium channel antagonists, adenosine, or nitroprusside. Patients undergoing balloon angioplasty of saphenous vein graft lesions and primary angioplasty in the setting of acute MI with a large amount of adherent thrombus are at greatest risk for distal embolization.

Restenosis after balloon angioplasty necessitating a second revascularization procedure is a major limitation that occurs in about 15-30% of patients, depending on the definition of restenosis applied. With the advent of DESs, restenosis rates have fallen to less than 10%.

Some of the very rare but serious complications of PCI are stroke, MI, and death. With advances in technique, technology, and adjuvant medical therapy, PCI is now associated with mortality and emergency bypass rates lower than 1%. The rate of nonfatal MI after coronary angioplasty ranges from 5% to 15%, whereas the rate after stent placement ranges from 2% to 5%.


After balloon angioplasty or stent implantation, the vessel wall undergoes a number of changes. Platelets and fibrin adhere to the site within minutes of vessel injury. Within hours to days, inflammatory cells infiltrate the site, and vascular smooth muscle cells begin to migrate toward the lumen.

The vascular smooth muscle cells then undergo hypertrophy and excrete an extensive extracellular matrix. During this period of vascular smooth muscle cell proliferation, endothelial cells colonize the surface of the lumen and regain their normal function.

Over the course of several weeks to months, multiple forces interact to cause remodeling of the vessel wall with either a decrease in lumen diameter (negative remodeling) or an increase in lumen diameter (positive remodeling). The amount of late loss in lumen diameter is dependent on the amount of neointimal proliferation and the degree of remodeling after intervention (see the image below). After 6 months, the repair process stabilizes and the risk of restenosis decreases significantly.

Mechanism of restenosis following percutaneous tra Mechanism of restenosis following percutaneous transluminal coronary angioplasty (PTCA).

Several studies have shown that the lumen diameter or area after treatment is one of the major predictors of restenosis. The use of coronary artery stents has decreased the rate of restenosis by improving the acute gain achieved and by minimizing negative remodeling.

Depending on the definition used, angiographic restenosis has been reported in as many as 50% of patients within 6 months after balloon angioplasty, necessitating repeat target-vessel revascularization in approximately 20-30% of patients. As noted (see above), DESs have reduced restenosis rates to less than 10%. Poststenting lumen diameter and lesion complexity are still the major predictors of restenosis with these newer stents.

Stent thrombosis

Although DESs have significantly reduced the incidence of restenosis, early generations of these devices were linked with concerns regarding stent thrombosis. Currently, the thrombosis rate for a DES is virtually identical to that for a BMS at 1 year (0.5-0.7%). The NORSTENT study reported that the rates of definite stent thrombosis were 0.8% with DESs and 1.2% with BMSs (P = 0.05) over 6 years of follow-up.[114]  Late stent thrombosis (>1 year), which occurred with early-generation DESs, is rarely seen with current DESs.

The factor that makes the greatest contribution to stent thrombosis is interruption of antiplatelet therapy. Current guidelines recommend a minimum of 1 year of DAPT for DES patients with acute coronary syndrome, 6 months of DAPT for stable DES patients, and 1 month ofDAPT for BMS patients.[4] DESs take longer to endothelialize on the coronary vessel wall than BMSs do, and discontinuing DAPT may expose patients to an increased risk for stent thrombosis over time.

In some clinical situations (eg, before urgent noncardiac surgery in which antiplatelet therapy may have to be discontinued and when known or potential medicine compliance issues are present), implanting a bare-metal stent during PCI may be preferred to implanting a DES. Another important factor is final stent diameter and area.

Underdeployment or incomplete apposition of any stent increases the risk of stent thrombosis. Stone et al found that although stent thrombosis is infrequent, it results in higher rates of MI and death.[115]

An analysis of data from 7090 consecutive PCI-treated patients in the ISAR-ASPI (Intracoronary Stenting and Antithrombotic Regimen-ASpirin and Platelet Inhibition) registry suggested that high platelet reactivity in patients on aspirin (HAPR) at the time of PCI was associated with a greater risk of death or stent thrombosis (6.2% vs 3.7% for non-HAPR) during the first year after PCI.[116] Moreover, HAPR independently predicted death or stent thrombosis at 1 year. These findings may support use of HAPR as a prognostic biomarker in PCI-treated patients.



Medication Summary

The goals of pharmacotherapy in percutaneous coronary intervention (PCI) are to reduce morbidity and prevent complications.

Anticoagulants, Hematologic

Class Summary

Anticoagulants prevent recurrent or ongoing thromboembolic occlusion of the vertebrobasilar circulation.


Heparin has been a traditional adjunctive medical therapy for patients undergoing coronary angioplasty and has been shown to decrease complications after the procedure. It augments the activity of antithrombin III and prevents conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. Heparin prevents the recurrence of a clot after spontaneous fibrinolysis.


Argatroban is a selective thrombin inhibitor that inhibits thrombin formation by binding to the active thrombin site of free and fibrin-bound thrombin. It inhibits thrombin-induced platelet aggregation.

Bivalirudin (Angiomax)

Bivalirudin inhibits coagulant effects by preventing thrombin-mediated cleavage of fibrinogen to fibrin.

Antiplatelet Agents, Cardiovascular

Class Summary

Agents in this class inhibit the activation of factors responsible for platelet aggregation.

Cangrelor (Kengreal)

Cangrelor is a fast-acting and rapidly reversible intravenous (IV) P2Y12 platelet inhibitor. It is indicated as an adjunct to PCI to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein (GP) IIb/IIIa inhibitor. Once the cangrelor IV infusion is discontinued following PCI, patients are transitioned to an oral P2Y12 platelet inhibitor (eg, clopidogrel, prasugrel, or ticagrelor).

Clopidogrel (Plavix)

Clopidogrel selectively inhibits the P2Y12 receptor on platelets and prevents adenosine diphosphate (ADP)-mediated activation of GPIIb/IIIa complex, thereby inhibiting platelet aggregation. It is a prodrug that must undergo activation to an active form.

Prasugrel (Effient)

Prasugrel is an oral P2Y12 platelet inhibitor. It is indicated for reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome (ACS) managed by means of PCI who have either (a) unstable angina or non-ST-elevation MI (NSTEMI) or (b) ST-elevation MI (STEMI) when managed with primary or delayed PCI. Prasugrel is a prodrug that must be converted to an active form. No cases of resistance have been reported.

Ticagrelor (Brilinta)

Ticagrelor is an oral P2Y12 platelet inhibitor. It is indicated to reduce the rate of thrombotic cardiovascular events in patients with ACS. In patients treated with PCI, it also reduces the rate of stent thrombosis.

Aspirin (Ascriptin Maximum Strength, Bayer Aspirin Extra Strength, Bufferin, Ecotrin, Tri-Buffered Aspirin)

Aspirin has been a traditional adjunctive medical therapy for patients undergoing coronary angioplasty and has been shown to decrease complications after the procedure. It is used as part of the regimen with P2Y12 platelet inhibitors. Aspirin is an odorless, white, powdery substance available at 81 mg, 325 mg, and 500 mg for oral use. When exposed to moisture, aspirin hydrolyzes into salicylic acid and acetic acids.

Aspirin is a stronger inhibitor of both prostaglandin synthesis and platelet aggregation than other salicylic acid derivatives. The acetyl group is responsible for inactivation of cyclooxygenase via acetylation. Aspirin is hydrolyzed rapidly in plasma, and elimination follows zero-order pharmacokinetics.

It irreversibly inhibits platelet aggregation by inhibiting platelet cyclooxygenase. This, in turn, inhibits conversion of arachidonic acid to PGI2 (potent vasodilator and inhibitor of platelet activation) and thromboxane A2 (potent vasoconstrictor and platelet aggregate). Platelet-inhibition lasts for the life of the cell (~10 days). It may be used in low doses to inhibit platelet aggregation and improve complications of venous stases and thromboses. It reduces the likelihood of myocardial infarction and is very effective in reducing the risk of stroke. Early administration of aspirin in patients with acute myocardial infarction may reduce cardiac mortality in the first month.

Abciximab (ReoPro)

Abciximab is a chimeric human-murine monoclonal antibody that has been approved for use in elective/urgent/emergent PCI. It binds to the receptor with high affinity and reduces platelet aggregation by 80% for up to 48 hours following infusion.

Eptifibatide (Integrilin)

Eptifibatide is a reversible antagonist of the GPIIb/IIIa receptor that inhibits platelet aggregation. Its effects persist over the duration of the maintenance infusion and are eliminated within a few hourswhen the infusion ends.

Tirofiban (Aggrastat)

Tirofiban is a nonpeptide antagonist of the GPIIb/IIIa receptor. It is a reversible antagonist of fibrinogen binding. When tirofiban is administered IV, more than 90% of platelet aggregation is inhibited.


Questions & Answers


When are distal embolic protection devices used in percutaneous coronary intervention (PCI)?

What is percutaneous coronary intervention (PCI)?

For which coronary conditions is percutaneous coronary intervention (PCI) indicated?

What are the contraindications for percutaneous coronary intervention (PCI)?

When is percutaneous coronary intervention (PCI) indicated in patients with stable angina?

When is percutaneous coronary intervention (PCI) indicated in patients with STEMI?

When is percutaneous coronary intervention (PCI) indicated in patients with NSTE-ACS?

What are the features of balloon catheters used in percutaneous coronary intervention (PCI)?

What are the features of the atherectomy devices used in percutaneous coronary intervention (PCI)?

What are the features of the intracoronary stents used in percutaneous coronary intervention (PCI)?

When is thrombus aspiration performed in percutaneous coronary intervention (PCI)?

When are intravascular ultrasonography (IVUS) and optical coherence tomography (OCT) indicated in percutaneous coronary intervention (PCI)?

What is the role of intracoronary pressure wires in percutaneous coronary intervention (PCI)?

What is included in antithrombotic therapy for percutaneous coronary intervention (PCI)?

What is included in antiplatelet therapy for percutaneous coronary intervention (PCI)?

What is included in glycoprotein inhibitor therapy for percutaneous coronary intervention (PCI)?

How has the use of percutaneous coronary intervention (PCI) evolved?

When is percutaneous coronary intervention (PCI) indicated?

What are the clinical contraindications for percutaneous coronary intervention (PCI)?

What are possible anatomic contraindications for percutaneous coronary intervention (PCI)?

When should percutaneous coronary intervention (PCI) be considered as an alternative to coronary artery bypass grafting (CABG)?

What is the role of percutaneous coronary intervention (PCI) in asymptomatic coronary disease?

What outcomes have been reported for same-day discharge after percutaneous coronary intervention (PCI)?

How do the outcomes of percutaneous coronary intervention (PCI) compare to those of medical therapy for treatment of stable angina?

How do the outcomes of percutaneous coronary intervention (PCI) compare to those of surgical revascularization for treatment of stable angina?

What outcomes have been reported for the use of bare-metal stents (BMS) in percutaneous coronary intervention (PCI)?

What outcomes have been reported for the use of drug-eluting stents (DESs) in percutaneous coronary intervention (PCI)?

What outcomes have been reported for percutaneous coronary intervention (PCI) to treat CAD in patients with comorbid diabetes?

What are the strategies for use of percutaneous coronary intervention (PCI) to treat NSTE-ACS?

What is the efficacy of percutaneous coronary intervention (PCI) in the treatment of NSTE-ACS?

What are the ACCF/AHA guidelines for use of percutaneous coronary intervention (PCI) in the treatment of NSTE-ACS?

What are the strategies for use of percutaneous coronary intervention (PCI) to treat STEMI?

What is the efficacy of percutaneous coronary intervention (PCI) in the treatment of STEMI?

What are the ACCF/AHA guidelines for use of percutaneous coronary intervention (PCI) in the treatment of STEMI?

How does intracoronary abciximab administration affect the outcome of percutaneous coronary intervention (PCI) for the treatment of STEMI?

What is the efficacy of drug-eluting stents (DESs) and bare-metal stents (BMSs) used in percutaneous coronary intervention (PCI) for the treatment of STEMI?

What is the prevalence of no-reflow following percutaneous coronary intervention (PCI) for the treatment of STEMI and how does it affect outcomes?

Periprocedural Care

What are the different types of devices used to perform percutaneous coronary intervention (PCI)?

What is the role of balloon catheters in percutaneous coronary intervention (PCI)?

What is the role of atherectomy devices in percutaneous coronary intervention (PCI)?

What is the role of intracoronary stents in percutaneous coronary intervention (PCI)?

What is the role of thrombectomy in percutaneous coronary intervention (PCI)?

What is the role of distal embolic protection devices in percutaneous coronary intervention (PCI)?

What is the role of vascular closure devices in percutaneous coronary intervention (PCI)?

What is included in preoperative care prior to performing percutaneous coronary intervention (PCI)?

How is anesthesia administered for percutaneous coronary intervention (PCI)?

What is the role of left ventricular end-diastolic pressure (LVEDP)-guided hydration in percutaneous coronary intervention (PCI)?


What are the routes of access used in percutaneous coronary intervention (PCI)?

What are the guidelines on access route selection for percutaneous coronary intervention (PCI)?

How is percutaneous coronary intervention (PCI) performed?

When is the access sheath removed following percutaneous coronary intervention (PCI)?

What is the role of intravascular ultrasonography (IVUS) in the anatomic assessment for percutaneous coronary intervention (PCI)?

What is the role of optical coherence tomography (OCT) in the anatomic assessment for percutaneous coronary intervention (PCI)?

What is the role of fractional flow reserve (FFR) monitoring during percutaneous coronary intervention (PCI)?

What is the role of antithrombotic therapy following percutaneous coronary intervention (PCI)?

What is the role of antiplatelet therapy following percutaneous coronary intervention (PCI)?

What is the role of glycoprotein inhibitor therapy following percutaneous coronary intervention (PCI)?

What are the possible complications of percutaneous coronary intervention (PCI)?

What is the prevalence of restenosis following percutaneous coronary intervention (PCI) and how is it treated?

What is the prevalence of stent thrombosis following percutaneous coronary intervention (PCI) and how is it treated?


Which medications in the drug class Antiplatelet Agents, Cardiovascular are used in the treatment of Percutaneous Coronary Intervention (PCI)?

Which medications in the drug class Anticoagulants, Hematologic are used in the treatment of Percutaneous Coronary Intervention (PCI)?