Acute Coronary Syndrome Guidelines

Updated: Sep 30, 2020
  • Author: David L Coven, MD, PhD; Chief Editor: Eric H Yang, MD  more...
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Guidelines Summary

Acute Coronary Syndromes Clinical Practice Guidelines (ESC, 2020)

In late August 2020, the European Society of Cardiology (ESC) released their updated guidelines for the diagnosis and management of non ST-elevation (NSTE) acute coronary syndrome (ACS). [1, 104] The updates place increased reliance on high-sensitivity cardiac troponin testing (hs-cTn) for diagnosis, embrace coronary computed tomography (CT) imaging to rule out lower-risk patients, as well as highlight the need for personalized antiplatelet regimens, systems of care, and quality improvement. Key messages are below.


Chest discomfort without persistent ST-segment elevation (NSTE-ACS) is the main symptom that initiates the diagnostic and therapeutic chain. The myocardial pathology consists of cardiomyocyte necrosis, measured by troponin release, or, less often, myocardial ischemia without cell damage (unstable angina). Those with unstable angina have a much lower death risk and benefit less from an aggressive pharmacologic and invasive approach.

Troponin assays and other biomarkers

The ESC recommends Hs-cTn assays over less sensitive assays (higher diagnostic accuracy, same low cost). Note that many cardiac conditions other than myocardial infarction (MI) also result in cardiomyocyte injury and can raise cTn levels.

Biomarkers such as creatine kinase myocardial band (CK-MB) and copeptin may be clinically relevant in specific circumstances when used with non hs-cTn T or I (T/I). There is a more rapid post-MI reduction of CK-MB, and it may have an added value for detecting early reinfarction. Routine use of copeptin is recommended as an additional biomarker for the early exclusion of MI in the infrequent setting of unavailable hs-cTn assays.

Rapid “rule-in” and “rule-out” algorithms

Use of hs-cTn assays (higher sensitivity, diagnostic accuracy) can shorten the time interval to the second cTn assessment for detecting MI at presentation. Recommendations include using the 0 h/1 h algorithm (best option, blood draw at 0 h and 1 h) or the 0 h/2 h algorithm (second-best option, blood draw at 0 h and 2 h). Use of the 0 h/1 h and 0 h/2 h algorithms with clinical and electrocardiographic (ECG) findings aid in identifying appropriate candidates for early discharge and outpatient management.

Hs-cTn confounders

Four clinical variables affect hs-cTn levels besides the presence/absence of MI, as follows:

  • Age: Up to 300% differences in concentration between healthy very young versus “healthy” very old individuals
  • Renal dysfunction: Up to 300% differences in concentration between otherwise healthy patients with very high versus very low estimated glomerular filtration rate (eGFR)
  • Chest pain onset: Over 300%
  • Sex: About 40%

Ischemic and bleeding risk assessments

Initial cTn levels add prognostic information about short- and long-term mortality to clinical and ECG variables (higher hs-cTn levels raise mortality risk). Measure serum creatinine and eGFR in all patients with NSTE-ACS; they are prognostic factors and key elements of the Global Registry of Acute Coronary Events (GRACE) risk score (superior assessment to subjective physician assessment for the occurrence of death or MI). Natriuretic peptides may add incremental prognostic information and may aid in risk stratification.

Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a pragmatic approach for evaluating bleeding risk (includes the most recent trials of HBR patients previously excluded from clinical trials of dual antiplatelet therapy [DAPT] duration or intensity). The PRECISE-DAPT (PRE dicting bleeding omplications n patients undergoing tent implantation and subsEquent DAPT) score may be used to guide and inform decision making on DAPT duration with a modest predictive value for major bleeding. Their value in improving patient outcomes remains unclear.

Noninvasive imaging

After MI has been excluded, elective noninvasive/invasive imaging may still be indicated based on clinical assessment. Coronary CT angiography (CCTA) may be an option in those with a low-to-modest clinical likelihood of unstable angina as a normal scan excludes coronary artery disease (CAD): It has a high negative predictive value (NPV) to rule out ACS (by excluding CAD) and a positive outcome in patients presenting to the emergency department with a low-to-intermediate pretest probability for ACS and a normal CCTA. Upfront imaging with CCTA also reduces the need for invasive coronary angiography (ICA) in high-risk patients. Other imaging options based on risk evaluation include stress imaging by cardiac magnetic resonance imaging (CMRI), stress echocardiography, or nuclear imaging.

Risk Stratification for an Invasive Approach

The ESC recommends an early routine invasive approach within 24 hours of admission for NSTEMI (based on hs-cTn levels, GRACE risk score >140, and dynamic new/presumably new ST-segment changes) to improve major adverse cardiac events and possibly early survival. Highly unstable patients require immediate invasive angiography based on hemodynamic status, arrhythmias, acute heart failure, or persistent chest pain. For all other clinical presentations, a selective invasive approach may be performed based on noninvasive testing or clinical risk assessment.

Revascularization Strategies

The main technical aspects of percutaneous coronary intervention (PCI) in NSTE-ACS patients do not differ from the invasive assessment and revascularization strategies for other manifestations of CAD. Radial access is the recommended and preferred approach in NSTE-ACS patients undergoing invasive assessment with or without PCI. As NSTE-ACS commonly involves multivessel disease, base the determination of revascularization timing and completeness on the functional relevance of all stenoses, patient age and comorbidities, general clinical condition, and left ventricular function.

MI With Nonobstructive Coronary Arteries (MINOCA)

MINOCA comprises a heterogeneous group of underlying causes potentially involving both coronary and noncoronary pathologic conditions, with the latter including cardiac and extra-cardiac disorders. By consensus, myocarditis and Takotsubo syndrome are excluded. CMRI, a key diagnostic tool, identifies the underlying cause in over 85% of patients and the subsequent appropriate treatment.

Spontaneous Coronary Artery Dissection

Spontaneous coronary artery dissection is a nonatherosclerotic, nontraumatic, or iatrogenic separation of the coronary arterial tunics due to vasa vasorum hemorrhage or intimal tear. It comprises up to 4% of all ACS but has a higher reported incidence (22-35% of ACS) in women younger than age 60 years. Intracoronary imaging is very useful for the diagnosis and treatment strategy. Medical treatment remains to be established.

Pretreatment With P2Y12 Receptor Inhibitors

Due to a lack of established benefit, the ESC does not recommend routine pretreatment with a P2Y12 receptor inhibitor in NSTE-ACS patients with unknown coronary anatomy and a planned early invasive management. However, it may be considered in selected cases and based on the patient’s bleeding risk.

Posttreatment APT

Barring contraindications, DAPT consisting of a 12-month regimen of a potent P2Y12 receptor inhibitor plus aspirin is generally recommended, regardless of the stent type. DAPT duration can be shortened (< 12 months), extended (>12 months), or modified by switching DAPT or de-escalation, based on individual clinical judgment according to the patient’s ischemic and bleeding risks, the occurrence of adverse events, comorbidities, co-medications, and the availability of the respective drugs.

Triple Antithrombotic Therapy (TAT)

In at least 6-8% of patients undergoing PCI, long-term oral anticoagulation is indicated and should be continued. For eligible patients, non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists (VKAs). The ESC recommends dual antithrombotic therapy (DAT) with a NOAC for stroke prevention and single antiplatelet therapy (SAPT) (clopidogrel is preferred) as the default strategy up to 12 months after a short period up to 1 week of TAT (NOAC + DAPT). TAT may be prolonged up to 1 month when the ischemic risk outweighs the bleeding risk.

Chronic coronary syndromes clinical practice guidelines (2019)

In August 2019, the European Society of Cardiology (ESC) released updated recommendations to their 2013 guidelines for the diagnosis and management of chronic coronary syndromes (CCS) (formerly stable coronary artery disease [CAD]). [105, 106]

The ESC introduced the term CCS in 2018 for what has been known as stable CAD to bring the terminology more in line with contemporary understanding of its development, progression, and management. The ESC indicates that “the clinical presentations of CAD can be categorized as either acute coronary syndrome (ACS) or CCS,” and that “CAD is a dynamic process” of atherosclerosis and altered arterial function “that can be modified by lifestyle, pharmacological therapies, and revascularization, which result in disease stabilization or regression.” CCS is also viewed as a type of out-of-hospital counterpart to ACS.

The updated guidelines define six clinical scenarios that reflect the heterogeneous nature of CCS, each defined by its own set of diagnostic and therapeutic concerns, as follows:

  • Suspected CAD with "stable" anginal symptoms, with or without dyspnea
  • Suspected CAD with new-onset heart failure symptoms or left ventricular (LV) dysfunction
  • Asymptomatic or stabilized symptomatic within 1 year of an ACS episode or following recent coronary revascularization
  • Asymptomatic or symptomatic more than 1 year after the initial diagnosis or revascularization
  • Angina and suspected vasospastic or microvascular disease
  • Asymptomatic with CAD detected at screening

The new phrase “clinical likelihood of CAD” uses various CAD risk factors as modifiers of pretest probability (PTP).

New Recommendations

Basic testing, diagnostics, and risk assessment

It is recommended that the initial test for diagnosing CAD in symptomatic patients in whom obstructive CAD cannot be ruled out based on clinical assessment alone be noninvasive functional imaging for myocardial ischemia or coronary computed tomography angiography (CTA). If coronary CTA reveals CAD of uncertain functional significance or is not diagnostic, functional imaging for myocardial ischemia is recommended.

The choice of the initial noninvasive diagnostic test is based on the clinical likelihood of CAD as well as other patient characteristics that influence test performance, local expertise, and the availability of tests.

Invasive angiography is recommended as an alternative test to diagnose CAD in patients with a high clinical likelihood and severe symptoms refractory to medical therapy, or typical angina at a low level of exercise and clinical evaluation that indicates high event risk. Invasive functional assessment must be available and used to evaluate stenoses before revascularization, unless the stenoses are very high grade (>90% diameter stenosis).

Consider the use of invasive coronary angiography with the availability of invasive functional evaluation to confirm the diagnosis of CAD in patients with an uncertain diagnosis on noninvasive testing.

Consider coronary CTA as an alternative to invasive angiography if another noninvasive test is equivocal or nondiagnostic. However, coronary CTA is not recommended in the setting of extensive coronary calcification, irregular heart rate, significant obesity, inability to cooperate with breath-hold commands, or any other conditions that would make good image quality unlikely.

When screening for CAD in asymptomatic patients, carotid ultrasound intima-media thickness (IMT) is not recommended for cardiovascular (CV) risk assessment.

Antithrombotic therapy

In patients with CCS and sinus rhythm, consider the addition of a second antithrombotic drug to aspirin for long-term secondary prevention in patients with a high risk  of ischemic events and without a high bleeding risk. This drug regimen may be considered in those with at least a moderately increased risk of ischemic events and without a high bleeding risk.

In patients with CCS and atrial fibrillation (AF) in whom oral anticoagulation (OAC) is initiated and who are eligible for a non-vitamin K antagonist OAC (NOAC), NOAC is preferred to a vitamin K antagonist (VKA). Long-term OAC therapy (a NOAC or VKA with time in the therapeutic range >70%):

  • Is recommended in patients with AF and a CHA 2DS 2- VASc score of at least 2 in males and at least 3 in females (CHA 2DS 2- VASc: ardiac failure, ypertension, ge ≥75 [doubled], iabetes, troke [doubled], ascular disease, ge 65-74, Sex [female])
  • Should be considered in patients with AF and a CHA 2DS 2- VASc score of 1 in males and 2 in females

In post-percutaneous coronary intervention (PCI) patients with AF or another indication for OAC:

  • In those eligible for a NOAC, NOAC (apixaban 5 mg bid, dabigatran 150 mg bid, edoxaban 60 mg od, or rivaroxaban 20 mg od) is preferred to a VKA in combination with antiplatelet therapy.
  • When rivaroxaban is used and concerns about high bleeding risk outweigh those about stent thrombosis or ischemic stroke, consider rivaroxaban 15 mg od over rivaroxaban 20 mg od for the duration of the concomitant single or dual antiplatelet therapy (DAPT).
  • When dabigatran is used and concerns about high bleeding risk outweigh those about stent thrombosis or ischemic stroke, consider dabigatran 110 mg bid over dabigatran 150 mg bid for the duration of the concomitant single or dual antiplatelet therapy.
  • After uncomplicated PCI, consider early aspirin cessation (≤1 week), and continuation of dual therapy with OAC and clopidogrel, if there is a low risk of stent thrombosis or if concerns about bleeding risk outweigh those about the risk of stent thrombosis, irrespective of the type of stent used.
  • Consider triple therapy with aspirin, clopidogrel, and an OAC for at least 1 month when the risk of stent thrombosis outweighs the bleeding risk, with the total duration (≤6 months) decided upon according to the assessment of these risks and clearly specified at hospital discharge.
  • In patients with an indication for a VKA in combination with aspirin and/or clopidogrel, carefully regulate the VKA dose intensity with a target international normalized ratio (INR) in the range of 2.0-2.5 and with time in the therapeutic range above 70%.
  • In patients with a moderate or high risk of stent thrombosis, irrespective of the type of stent used, dual therapy with an OAC and either ticagrelor or prasugrel may be considered as an alternative to triple therapy with an OAC, aspirin, and clopidogrel.

Other pharmacotherapy

Concomitant use of a proton pump inhibitor is recommended in patients receiving aspirin monotherapy, DAPT, or OAC monotherapy who are at high risk of gastrointestinal bleeding.

Lipid-lowering drugs:

  • If goals are not achieved with the maximum tolerated statin dose: Combination with ezetimibe is recommended.
  • For patients at very high risk who do not achieve their goals on a maximum tolerated dose of statin and ezetimibe: Combination with a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor is recommended.

Consider angiotensin-converting enzyme inhibitors in CCS patients at very high risk of CV adverse events.

In patients with diabetes mellitus and CV disease (CVD):

  • The sodium-glucose co-transporter 2 inhibitors empagliflozin, canagliflozin, or dapagliflozin are recommended.
  • A glucagon-like peptide-1 receptor agonist (liraglutide or semaglutide) is recommended.

Treatment options for refractory angina

A reducer device for coronary sinus constriction may be considered to ameliorate symptoms of debilitating angina refractory to optimal medical and revascularization strategies.

For more information, please go to Primary and Secondary Prevention of Coronary Artery Disease, Acute Coronary Syndrome, and Atrial Fibrillation.


In 2015, the American College of Physicians (ACP) released guidelines on screening for coronary heart disease, including the following [15] :

  • There is no evidence that cardiac screening improves patient outcomes in asymptomatic, low-risk adults.
  • Potential harms of cardiac screening include false-positive results causing patients to undergo potentially unnecessary tests and procedures.
  • Among adults at low risk, prevalence of coronary heart disease is low, and cardiac screening is of low predictive value. Therefore, cardiac screening is of low yield, and the probability that positive findings will influence therapeutic decision making is low.
  • Clinicians should therefore emphasize strategies to reduce cardiovascular risk even further among low-risk adults by treating modifiable risk factors (smoking, diabetes, blood pressure, hyperlipidemia, overweight, and exercise).
  • Clinicians should not screen asymptomatic, low-risk adults for cardiac disease using resting or stress electrocardiography, stress echocardiography, or stress myocardial perfusion imaging.
  • Clinicians should conduct cardiovascular risk assessment with a global risk score combining individual risk factor measurements into a single quantitative estimate of risk.
  • The ACP recommendations do not apply to symptomatic patients or to screening athletes before participation in various events.

Management guidelines

The American College of Cardiology in conjunction with with the American Heart Association (AHA/ACC) and the European Society of Cardiology (ESC) have developed guidelines for management of patients with ST-segment elevation myocardial infarction (STEMI) [107, 108, 109, 110] and non-ST-elevation acute coronary syndromes (NSTE-ACS) [111, 112] which focus primarily on treatment in a hospital setting. Guidelines with specific recommendations for prehospital and emergency department (ED) management of patients with ACS were included in the 2015 revised international consensus guidelines on cardiopulmonary resuscitation and emergency cardiovascular care issued by the International Liaison Committee on Resuscitation (ILCOR). [113]


The 2015 ILCOR recommendations for diagnostic interventions in ACS include the following:

  • Prehospital 12-lead electrocardiographic (ECG) acquisition with hospital notification should be obtained for adult patients with suspected STEMI (strong recommendation, low-quality evidence).
  • Computer-assisted ECG interpretation can be used as an adjunct to identify STEMI (weak recommendation, very-low-quality evidence), but it should not be used alone to rule out STEMI because of the poor sensitivity of the computer algorithms evaluated (weak recommendation, very-low-quality evidence).
  • For patients with suspected STEMI outside of a hospital setting, nonphysicians may perform ECG interpretation to recognize STEMI in a system where the false-positive (FP) and false-negative (FN) rates are low (weak recommendation, very-low-quality evidence).
  • When primary percutaneous coronary intervention (PPCI) is the planned strategy, prehospital activation of the catheterization laboratory for PPCI is preferred (strong recommendation, very-low-quality evidence).
  • The use of troponins at 0 and 2 hours as a stand-alone measure for excluding the diagnosis of ACS is strongly discouraged (strong recommendation, very-low-quality evidence). Excluding the diagnosis of ACS can be accomplished by combining negative high-sensitivity cardiac troponin (hs-cTnI) measured at 0 and 2 hours with low-risk stratification or by combining negative cardiac troponin I (cTnI) or cardiac troponin T (cTnT) measured at 0 and 3 to 6 hours with very low risk stratification (weak recommendation, low-quality evidence).

The 2014 AHA/ACC revision of their 2007 guidelines for the management of NSTE-ACS includes the following recommendations for evaluation of patients with suspected ACS, as summarized below. [112]

Class I

  • Risk stratify patients with suspected ACS based on the likelihood of ACS and adverse outcome(s) to decide on the need for hospitalization and to assist in the selection of treatment options. (Level of evidence: B)
  • Immediately refer patients with suspected ACS and high-risk features (eg, continuing chest pain, severe dyspnea, syncope/presyncope, or palpitations) to the emergency department (ED) and transport by emergency medical services when available. (Level of evidence: C)
  • In patients with chest pain or other symptoms suggestive of ACS, perform a 12-lead ECG and evaluate for ischemic changes within 10 minutes of the patient’s arrival at an emergency facility when possible. (Level of evidence: C)
  • Perform serial ECGs (eg, 15- to 30-minute intervals during the first hour) to detect ischemic changes if the initial ECG is not diagnostic but the patient remains symptomatic. (Level of evidence: C)
  • Obtain serial cardiac troponin I or T levels (when a contemporary assay is used) at presentation and 3 to 6 hours after symptom onset in all patients who present with symptoms consistent with ACS (to identify a rising and/or falling pattern of values). If the time of symptom onset is ambiguous, the time of presentation should be considered the time of onset for assessing troponin values. (Level of evidence: A)
  • Obtain additional troponin levels beyond 6 hours after symptom onset in patients with normal troponin levels on serial examination when changes on ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS. (Level of evidence: A)

Class IIa

  • It is reasonable to give low-risk patients who are referred for outpatient testing daily aspirin, short-acting nitroglycerin, and other medications if appropriate (eg, beta blockers), with instructions about activity level and clinician follow-up. (Level of evidence: C)
  • Observe patients with symptoms consistent with ACS but without objective evidence of myocardial ischemia (nonischemic initial ECG and normal cardiac troponin) in a chest pain unit or telemetry unit with serial ECGs and cardiac troponin at 3- to 6-hour intervals. (Level of evidence: B)
  • For patients with suspected ACS who have normal serial ECGs and cardiac troponin levels, it is reasonable to have obtain a treadmill ECG (Level of evidence: A), stress myocardial perfusion imaging, or stress echocardiography before discharge or within 72 hours after discharge. (Level of evidence: B)
  • In patients with suspected ACS but a normal ECG, normal cardiac troponin levels, and no history of coronary artery disease (CAD), it is reasonable to initially perform (without serial ECGs and troponins) coronary computed tomography angiography to assess the coronary artery anatomy (Level of evidence: A) or rest myocardial perfusion imaging with a technetium-99m radiopharmaceutical to exclude myocardial ischemia. (Level of evidence: B)

The 2015 European Society of Cardiology (ESC) guidelines are in general agreement with the 2014 AHA/ACC guidelines. [111] Additional Class I recommendations are summarized below:

  • Base the diagnosis and initial short-term ischemic and bleeding risk stratification on a combination of the clinical history, symptoms, vital signs, other physical findings, and ECG and laboratory results. (Level of evidence: A)
  • Measure cardiac troponin levels with sensitive or high-sensitivity assays, and obtain the results within 60 minutes of presentation. (Level of evidence: A)
  • Perform a rapid rule-out protocol at 0 h and 3 h if high-sensitivity cardiac troponin tests are available. (Level of evidence: B)
  • Perform a rapid rule-out and rule-in protocol at 0 h and 1 h if a high-sensitivity cardiac troponin test with a validated 0 h/1 h algorithm is available. Additional testing after 3–6 h is indicated if the first two troponin measurements are not conclusive and the patient's clinical condition remains suggestive of ACS. (Level of evidence: B)
  • Perform continuous rhythm monitoring until the diagnosis of non–ST-elevation myocardial infarction (NSTEMI) is established or ruled out.(Level of evidence: C)
  • In the absence of signs or symptoms of ongoing ischemia, rhythm monitoring in unstable angina may be considered in selected patients (eg, suspicion of coronary spasm or associated symptoms suggestive of arrhythmic events).

In addition, the ESC guidelines find the Global Registry of Acute Coronary Events (GRACE 2.0) risk calculation provides the most accurate stratification of risk both on admission and at discharge. [111] However, the guidelines caution that although its value as a prognostic assessment tool is clear, the impact of risk score implementation on patient outcomes has not been adequately investigated. Bleeding risk can be stratified using the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) risk score. [111]

Important considerations from the 2017 ESC guidelines for managing acute myocardial infarction in patients presenting with ST-segment elevation are summarized below. [109, 110]

Where fibrinolysis is the reperfusion strategy, the maximum time delay from the diagnosis of STEMI to treatment has been shortened from 30 minutes in 2012 to 10 minutes in 2017.

Complete revascularization in patients with multivessel disease receives a stronger recommendation, moving from class III (should not be performed) to class IIa (should be considered), with non–infarct-related arteries treated during the index procedure or another time point before discharge from the hospital.

Thrombus aspiration is no longer recommended, based on two large trials in more than 15,000 patients.

Deferred stenting, which involved opening the artery and waiting 48 hours to implant a stent, is no longer recommended.

For PCI, the use of drug-eluting stents instead of bare-metal stents has been upgraded from class IIa (should be considered) to class I (is recommended/indicated), as has the use of radial, instead of femoral, arterial access.

Dual antiplatelet therapy beyond 12 months may be considered in selected patients. Bivalirudin has been downgraded from class I to IIa (should be considered), and enoxaparin upgraded from class IIb (may be considered) to IIa (should be considered). Cangrelor (Kengreal), which was not mentioned in the 2012 document, has been recommended as an option in certain patients.

Additional lipid-lowering therapy is recommended in patients with high cholesterol despite taking the maximum dose of statins.

The cutoff for administering oxygen therapy has been lowered from less than 95% to less than 90% arterial oxygen saturation.

Left and right bundle branch block are now considered equal for recommending urgent angiography when patients have ischemic symptoms.

Selection of management strategy

Determination of the preferred management strategy depends on the patient’s clinical characteristics and clinical risk. The AHA/ACC and ESC provide similar recommendations for selection of the preferred management stategy, which are summarized in Table 3, below. [111, 112]

Table 3. Recommendations for Selection of Preferred Management Strategy (Open Table in a new window)

Preferred Strategy Patient Characteristic/Clinical Risk

Immediate invasive strategy

(< 2 hours)

Refractory angina
Signs or symptoms of heart failure, or new or worsening mitral regurgitation
Hemodynamic instability or cardiogenic shock
Recurrent angina/ischemia at rest, or with low-level activities despite intensive medical therapy
Sustained ventricular tachycardia or ventricular fibrillation
Ischemia-guided strategy Low-risk score (eg, TIMI 0 or 1, GRACE < 109)
Low-risk Tn-negative female
Patient or physician preference in the absence of high-risk features

Early invasive strategy

(< 24 hours)

GRACE score >140
Rise or fall in Tn compatible with MI
New or presumably new ST-segment depression

Delayed invasive strategy

(24-72 hours)

Diabetes mellitus
Renal insufficiency (GFR < 60 mL/min/1.73m2)
Reduced LV systolic function (LVEF < 40%)
Early postinfarction angina
PCI within 6 months
Prior CABG
GRACE score 109-140; TIMI Score ≥2
ACC/AHA = American College of Cardiology/American Heart Association; CABG = coronary artery bypass grafting; GRACE = Global Registry of Acute Coronary Events; LV = left ventricle; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIMI = Thrombolysis in Myocardial Infarction Clinical Trial; Tn = troponin.

Initial hospital care

The 2014 AHA/ACC recommendations for initial hospital care are summarized below. [112]


Administer supplemental oxygen only when the oxygen saturation falls below 90%, respiratory distress is present, or other high-risk features for hypoxemia are present. (Class I; level of evidence C)


Administer sublingual nitroglycerin (NTG) every 5 minutes up to 3 times for continuing ischemic pain, and then assess the need for intravenous (IV) NTG. (Class I; level of evidence: C)

Administer IV NTG for persistent ischemia, heart failure (HF), or hypertension. (Class I; level of evidence: B)

Nitrates are contraindicated with recent use of a phosphodiesterase inhibitor. (Class III; level of evidence: B)


IV morphine sulfate may be reasonable for continued ischemic chest pain despite maximally tolerated anti-ischemic medications. (Class IIb; level of evidence: B)

Nonsteroidal anti-inflammatories (NSAIDs) (except aspirin) should not be initiated and should be discontinued because of the increased risk of major adverse cardiac events (MACE) associated with their use. (Class III; level of evidence: B)

Beta-adrenergic blockers

Initiate oral beta blockers in the absence of HF, low-output state, risk for cardiogenic shock, or other contraindications to beta blockade. (Class I; level of evidence: A)

Use sustained-release metoprolol succinate, carvedilol, or bisoprolol for beta-blocker therapy in patients with concomitant NSTE-ACS, stabilized HF, and reduced systolic function (Class I; level of evidence: C)

Re-evaluate to determine subsequent eligibility in patients with initial contraindications to beta blockers. (Class I; level of evidence: C)

It is reasonable to continue beta-blocker therapy in patients with normal LV function with NSTE-ACS. (Class IIa; level of evidence: C)

IV beta blockers are potentially harmful when risk factors for shock are present. (Class III; level of evidence: B)

Calcium channel blockers (CCBs)

Administer initial therapy with nondihydropyridine CCBs in patients with recurrent ischemia and contraindications to beta blockers in the absence of LV dysfunction, increased risk for cardiogenic shock, PR interval longer than 0.24 s, or second- or third-degree atrioventricular block without a cardiac pacemaker. (Class I; level of evidence: B)

Administer oral nondihydropyridine calcium antagonists in patients with recurrent ischemia after use of beta blockers and nitrates in the absence of contraindications. (Class I; level of evidence: C)

CCBs are recommended for ischemic symptoms when beta blockers are not successful, are contraindicated, or cause unacceptable side effects. (Class I; level of evidence: C)

Long-acting CCBs and nitrates are recommended for patients with coronary artery spasm. (Class I; level of evidence: C)

Immediate-release nifedipine is contraindicated in patients with NSTE-ACS in the the absence of a beta blocker therapy (Class III; level of evidence: B)

Cholesterol management

Initiate or continue high-intensity statin therapy in patients with no contraindications. (Class I; level of evidence: A)

Obtain a fasting lipid profile in patients with NSTE-ACS, preferably within 24 hours of presentation. (Class IIa; level of evidence:C)

Angiotensin-converting enzyme (ACE) inhibitors

Class I

ACE inhibitors should be started and continued indefinitely in all patients with a left ventricular ejection fraction (LVEF) below 40% and in those with hypertension, diabetes mellitus, or stable chronic kidney disease (CKD), unless contraindicated. (Level of evidence: A)

Use angiotensin receptor blockers (ARBs) in patients with heart failure or MI with an LVEF below 40% who are ACE inhibitor intolerant. (Level of evidence: A)

Use aldosterone blockade in post–MI patients who are without significant renal dysfunction or hyperkalemia who are receiving therapeutic doses of ACE inhibitor and beta blockers and have an LVEF below 40%, diabetes mellitus, or heart failure. (Level of evidence: A)

Antiplatelet therapy

The 2014 AHA/ACC recommendations for initial antiplatelet/anticoagulation therapy in patients with NSTE-ACS are summarized below. [112]


Non–enteric-coated, chewable aspirin (162 mg to 325 mg) should be given to all patients without contraindications as soon as possible after presentation, and a maintenance dose of aspirin (81 mg/d to 325 mg/d) should be continued indefinitely. (Class I; level of evidence A)

In patients who are unable to take aspirin because of hypersensitivity or major gastrointestinal (GI) intolerance, administer a loading dose of clopidogrel followed by a daily maintenance dose. (Class I; level of evidence B)


Administer anticoagulation, in addition to antiplatelet therapy, for all patients, irrespective of the initial treatment strategy. Treatment options include the following (all Class I):

  • Subcutaneous (SC) enoxaparin for the duration of hospitalization or until PCI is performed (Level of evidence: A)
  • Bivalirudin until diagnostic angiography or PCI is performed in patients with early invasive strategy only (Level of evidence: B)
  • SC fondaparinux for the duration of hospitalization or until PCI is performed (Level of evidence: B)
  • IV unfractionated heparin (UFH) for 48 h or until PCI is performed (Level of evidence: B)

IV fibrinolytic treatment is not recommended in patients with NSTE-ACS. (Class III, level of evidence: A)

The 2017 ESC focused update recommendations for antiplatelet therapy in coronary artery disease are outlined below. [114, 115]

Predicting perioperative bleeding

Preoperative fibrinogen levels may be considered to identify patients at high risk of bleeding.

Routine use of viscoelastic and platelet function testing is not recommended to predict bleeding in patients without antithrombotic treatment.

Platelet function testing may be considered to guide the decision on the timing of cardiac surgery in patients who have recently received P2Y12 inhibitors or who have ongoing dual antiplatelet therapy (DAPT).

Managing preoperative anticoagulants and antiplatelet drugs

In patients undergoing coronary artery bypass grafting (CABG), acetylsalicylic acid (ASA) should be continued throughout the preoperative period.

In patients at high risk of bleeding or refusing blood transfusions and undergoing non-coronary cardiac surgery, stopping ASA should be considered at least 5 days preoperatively.

It is recommended that ASA be re(started) as soon as there is no concern over bleeding (within 24 hr) after isolated CABG.

In patients taking DAPT who need to have non-emergent cardiac surgery, postponing surgery for at least 3 days after discontinuation of ticagrelor, 5 days after clopidogrel, and 7 days after prasugrel should be considered.

It is recommended that GPIIb/IIIa inhibitors be discontinued at least 4 hours before surgery.

It is recommended that prophylactic low-molecular-weight heparin (LMWH) be discontinued 12 hours before surgery and fondaparinux 24 hours before surgery. A longer interval may be necessary for patients with impaired renal function and/or therapeutic doses.

Elective cardiac surgery should be performed if the international normalized ratio (INR) is < 1.5 in patients taking vitamin K antagonists (VKAs). When surgery cannot be postponed, coagulation factors should be used to reverse the effect.

In patients having elective cardiac surgery, direct oral anticoagulants (DOACs) should be stopped at least 48 hours before surgery. A longer interval may be necessary for patients with impaired renal function.

Preoperative anemia

Oral or intravenous iron alone prior to cardiac surgery may be considered in mildly anemic patients (women, hemoglobin (Hb) 100–120 g/L; men, Hb 100–130 g/L) or in severely anemic patients (both genders, Hb ≤100 g/L) to improve erythropoiesis.

Erythropoietin with iron supplementation should be considered to reduce postoperative transfusions in patients with non-iron deficiency (eg, erythropoietin (EPO), vitamin D, or folate acid deficiency) undergoing elective surgery.

Intraoperative anticoagulation

Heparin-level-guided heparin management should be considered over activated clotting time (ACT)-guided heparin management to reduce bleeding.

Heparin-level-guided protamine dosing may be considered to reduce bleeding and transfusions.

Protamine should be administered in a protamine-to-heparin dosing ratio < 1:1 to reduce bleeding.

Antithrombin (AT) supplementation is indicated in patients with AT deficiency to improve heparin sensitivity.

In patients with heparin-induced thrombocytopenia (HIT) antibodies for whom surgery cannot be postponed, anticoagulation with bivalirudin should be considered when the bleeding risk is acceptable. The use of heparin in the pre- and postoperative periods should be avoided.

Transfusion strategies

Implementation of a patient blood management protocol for the bleeding patient is recommended.

The use of packed red blood cells (PRBCs) of all ages is recommended, because the storage time of the PRBCs does not affect the outcomes.

The use of leukocyte-depleted PRBCs is recommended to reduce infectious complications.

Pooled solvent detergent fresh-frozen plasma (FFP) may be preferred to standard FFP to reduce the risk of transfusion-related acute lung injury.

Perioperative treatment algorithms for the bleeding patient based on viscoelastic point-of-care tests should be considered to reduce the number of transfusions.

Platelet concentrate should be transfused in bleeding patients with a platelet count below 50 (109/L) or patients on antiplatelet therapy with bleeding complications.

Dual antiplatelet therapy

In 2016, the ACC/AHA released updated guidelines on duration of dual antiplatelet therapy (DAPT) in patients with coronary artery disease. In this focused update, the term and acronym DAPT is used to specifically to refer to combination antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor).

Key recommendations for patients with NSTE-ACS or STEMI treated with DAPT are summarized below. [116]

Class I

For all patients treated with DAPT, a daily dose of aspirin 81 mg (range, 75 mg to 100 mg). (Level of evidence: B-R)

After implantation with a bare metal stent (BMS) or drug-eluting stent (DES), administer P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) for at least 12 months. (Level of evidence: B-R)

For patients who subsequently undergo coronary artery bypass grafting (CABG) after coronary stent implantation, resume P2Y12 inhibitor therapy postoperatively so that DAPT continues until the recommended duration of therapy is completed. (Level of evidence: C-EO)

In patients who undergo CABG, resume P2Y12 inhibitor therapy after CABG to complete 12 months of DAPT therapy. (Level of evidence: C-LD)

Patients with STEMI treated with fibrinolytic therapy should be continue P2Y12 inhibitor therapy (clopidogrel) for a minimum of 14 days (Level of evidence: A) and, ideally, at least 12 months. (Level of evidence: C-EO)

Class IIa

After coronary stent implantation, it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy. (Level of evidence: B-R)

After coronary stent implantation in patients who are not at high risk for bleeding complications and who do not have a history of stroke or transient ischemic attack (TIA), it is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 inhibitor therapy. (Level of evidence: B-R)

Class IIb

In patients treated with coronary stent implantation or fibrinolytic therapy who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk, it may be reasonable to continue DAPT (clopidogrel, prasugrel, or ticagrelor) for longer than 12 months. (Level of evidence: A)

After DES implantation, patients who develop a high risk of bleeding, are at high risk of severe bleeding complications, or develop significant overt bleeding, it may be reasonable to discontinue P2Y12 inhibitor therapy after 6 months. (Level of evidence: C-LD)

Class III

Prasugrel should not be administered to patients with a prior history of stroke or TIA. (Level of evidence: B-R)

Concomitant use of proton pump inhibitors and thienopyridines

A 2010 consensus statement issued by the ACC, American College of Gastroenterology (ACG), and AHA addressed the issue of concomitant use of proton pump inhibitors (PPIs) and thienopyridine antiplatelet drugs. [117] The recommendations are summarized below.

Clopidogrel reduces major cardiovascular (CV) events compared with placebo or aspirin.

Dual antiplatelet therapy with clopidogrel and aspirin, compared with aspirin alone, reduces major cardiovascular events and coronary stent thrombosis, but it is not routinely recommended for patients with prior ischemic stroke because of the risk of bleeding.

Clopidogrel alone, aspirin alone, and their combination are all associated with increased risk of GI bleeding.

Patients with prior GI bleeding are at highest risk for recurrent bleeding on antiplatelet therapy. Other clinical characteristics that increase the risk of GI bleeding include advanced age; concurrent use of anticoagulants, steroids, or NSAIDs including aspirin; and Helicobacter pylori infection. The risk of GI bleeding increases as the number of risk factors increases.

Use of a PPI or histamine H2 receptor antagonist (H2RA) reduces the risk of upper GI bleeding compared with no therapy. PPIs reduce upper GI bleeding to a greater degree than do H2RAs.

PPIs are recommended to reduce GI bleeding among patients with a history of upper GI bleeding. PPIs are appropriate in patients with multiple risk factors for GI bleeding who require antiplatelet therapy.

Routine use of either a PPI or an H2RA is not recommended for patients at a lower risk of upper GI bleeding.

Clinical decisions regarding concomitant use of PPIs and thienopyridines must balance overall risks and benefits, considering both cardiovascular and GI complications.


In August 2019, the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) released updates to their 2016 guidelines for the management of dyslipidemia. [118, 119] Among the changes are new and more aggressive proposed goals for low-density lipoprotein cholesterol (LDL-C) levels, revised cardiovascular (CV) risk stratification, particularly for patients at high to very high risk, as well as new patient management recommendations. [118, 119]

New LDL targets across CV risk categories are as follows:

  • For very-high-risk patients (10-year risk of CV death ≥10%): Use an LDL-C reduction of at least 50% from baseline and an LDL-C goal of below 1.4 mmol/L (< 55 mg/dL).
  • For very high-risk patients who experience a second vascular event within 2 years (not necessarily of the same type as the first event) while taking maximally tolerated statin therapy: An LDL-C goal of below 1.0 mmol/L (< 40 mg/dL) may be considered.
  • For patients at high risk (10-year risk for CV death of 5% to < 10%): Use an LDL-C reduction of at least 50% from baseline and an LDL-C goal of below 1.8 mmol/L (< 70 mg/dL).
  • For individuals at moderate risk (10-year risk for CV death of 1% to < 5%): Consider an LDL-C goal of below 2.6 mmol/L (< 100 mg/dL).
  • For individuals at low risk (10-year risk for CV death < 1%): Consider an LDL-C goal of below 3.0 mmol/L (< 116 mg/dL).

New Recommendations

Cardiovascular imaging for assessment of ASCVD risk (should be considered), as follows:

  • Consider assessment of carotid and/or femoral arterial plaque burden on arterial ultrasonography as a risk modifier in individuals at low or moderate risk.
  • Consider coronary artery calcium (CAC) score assessment with computed tomography (CT) as a risk modifier in the CV risk assessment of asymptomatic individuals at low or moderate risk.

Lipid analyses for CVD risk estimation (should be considered): Consider measurement of lipoprotein(a) (Lp(a)) at least once in each adult’s lifetime to identify those with very high inherited Lp(a) levels above 180 mg/dL (>430 nmol/L) who may have a lifetime risk of atherosclerotic CV disease (ASCVD) that is equivalent to the risk associated with heterozygous familial hypercholesterolemia (FH).

Pharmacotherapy of patients with hypertriglyceridemia (should be considered): In high-risk (or above) patients with triglyceride (TG) levels between 1.5 and 5.6 mmol/L (135-499 mg/dL) despite statin treatment, consider the combination of n-3 polyunsaturated fatty acids (PUFAs) (icosapent ethyl 2 × 2g/day) with statins.

Treatment of patients with heterozygous FH (should be considered): For primary prevention in individuals with FH at very-high risk, consider an LDL-C reduction of over 50% from baseline and an LDL-C goal below 1.4 mmol/L (< 55 mg/dL).

Recommendations for the treatment of dyslipidaemias in older people (aged >65 years) include the following:

  • For primary prevention in older people aged up to 75 years, statin therapy is recommended based on the level of risk.
  • For primary prevention in older people older than 75 years, initiation of statin treatment may be considered if they are at high risk or above.

Dyslipidemia therapy in the setting of diabetes mellitus inlcudes the following:

  • For patients with type 2 diabetes mellitus (T2DM) at very-high risk, an LDL-C reduction of at least 50% from baseline and an LDL-C goal of below 1.4 mmol/L (< 55mg/dL) is recommended.
  • For those with T2DM at high risk, an LDL-C reduction of at least 50% from baseline and an LDL-C goal of below 1.8 mmol/L (< 70 mg/dL) is recommended.
  • For individuals with T1DM who are at high or very-high risk, statins are recommended.
  • Consider intensification of statin therapy before introducing combination therapy. If the goal is not reached, consider a statin combined with ezetimibe. (Each should be considered.)
  • Statin therapy is not recommended in premenopausal diabetic patients who are considering pregnancy or who are not using adequate contraception.

Lipid-lowering therapy in patients with ACS (should be considered): For patients who present with an acute coronary syndrome (ACS), and whose LDL-C levels are not at goal despite already taking a maximally tolerated statin dose and ezetimibe, consider adding a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor early after the event (if possible, during hospitalization for the ACS event).

2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction

In 2015 the ACC, AHA, and Society for Cardiovascular Angiography and Interventions (SCAI) issued revised recommendations for PCI in STEMI patients, summarized below. [120]

Class IIb

PCI should not be performed in a noninfarct artery at the time of primary PCI in patients who are hemodynamically stable. (Level of evidence: B)

PCI of a noninfarct artery may be considered in selected patients with multivessel disease who are hemodynamically stable, either at the time of primary PCI or as a planned staged procedure. (Level of evidence: B-R)

The usefulness of selective and bailout aspiration thrombectomy in patients undergoing primary PCI is not well established. (Level of evidence: C-LD)

Class III

Routine aspiration thrombectomy before primary PCI is not useful. (Level of evidence: A)

Hospital discharge and follow-up

Selected Class 1 recommendations for post-hospital care from the 2014 AHA/ACC guidelines are summarized below. [112]

Inpatient medications to control ischemia should be continued after hospital discharge in patients with NSTE-ACS who do not undergo coronary revascularization, patients with incomplete or unsuccessful revascularization, and patients with recurrent symptoms after revascularization. Titration of the doses may be required. (Level of evidence: C)

All patients should be given sublingual or spray NTG with verbal and written instructions for its use. (Level of evidence: C)

Before hospital discharge, patients should be informed about symptoms of worsening myocardial ischemia and Ml, and they should be given verbal and written instructions about how and when to seek emergency care for such symptoms. (Level of evidence: C)

For post–NSTE-ACS patients who have initial angina lasting more than 1 minute, it is recommended that NTG (1 dose sublingual or spray) be taken if angina does not subside within 3 to 5 minutes; patients or bystanders should call 9-1-1 immediately to access emergency medical services. (Level of evidence: C)

If the pattern or severity of angina changes, suggesting worsening myocardial ischemia (eg, pain is more frequent or severe or is precipitated by less effort or occurs at rest), patients should contact their clinician without delay to assess the need for additional treatment or testing. (Level of evidence: C)

Before discharge, patients should be educated about modification of cardiovascular risk factors. (Level of evidence: C)

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