Unstable Angina Guidelines

Updated: Oct 01, 2020
  • Author: Walter Tan, MD, MS; Chief Editor: Eric H Yang, MD  more...
  • Print

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). [84, 85] 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.


2014 AHA/ACC and 2015 ESC Guidelines for the Management NSTE-ACS

Guidelines for the management of non–ST-elevation acute coronary syndromes (NSTE-ACS) have been issued by the American Heart Association/American College of Cardiology (AHA/ACC) in 2014 and the European Society of Cardiology (ESC) in 2015. A summary of these guidelines are below.

In 2014, the AHA/ACC published a full revision of their 2007 guidelines which included the following key changes [42] :

  • Because unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI) are on a pathophysiologic continuum and are often indistinguishable, they are considered together in the 2014 guidelines

  • To more clearly convey this physiology-based patient-management approach, the guideline has replaced the term "initial conservative management" with "ischemia-guided strategy"

  • Cardiac troponin assays may improve the diagnosis of myocardial necrosis

  • High-intensity statins should be used in patients with overt cardiovascular disease

  • Risk stratification tools in these patients include the Thrombolysis in Myocardial Infarction (TIMI) risk score and the Global Registry of Acute Coronary Events (GRACE) risk score

In 2015, the ESC released its guidelines which define unstable angina as "myocardial ischemia at rest or minimal exertion in the absence of cardiomyocyte necrosis." [86]


The 2014 AHA/ACC revised guidelines include the following recommendations for evaluation of patients with suspected ACS [42] :

Class I

Patients with suspected ACS should be risk stratified based on the likelihood of ACS and adverse outcome(s) to decide on the need for hospitalization and assist in the selection of treatment options. (Level of evidence: B)

Patients with suspected ACS and high-risk features such as continuing chest pain, severe dyspnea, syncope/presyncope, or palpitations should be referred immediately to the emergency department (ED) and transported by emergency medical services when available. (Level of evidence: C)

In patients with chest pain or other symptoms suggestive of ACS, a 12-lead electrocardiogram (ECG) should be performed and evaluated for ischemic changes within 10 minutes of the patient’s arrival at an emergency facility. (Level of evidence: C)

Serial ECGs (eg, 15- to 30-minute intervals during the first hour) should be performed to detect ischemic changes if the initial ECG is not diagnostic but the patient remains symptomatic. (Level of evidence: C)

Serial cardiac troponin I or T levels (when a contemporary assay is used) should be obtained 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)

Additional troponin levels should be obtained 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 medication 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 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 levels at 3- to 6-hour intervals. (Level of evidence: B)

For patients with possible ACS who have normal serial ECGs and cardiac troponin levels, it is reasonable to 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 possible ACS and 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 troponin levels) coronary computed tomography angiography to assess 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 ESC guidelines are in general agreement with the 2014 AHA/ACC. Additional Class I recommendations are summarized below [86]

Base the diagnosis and initial short-term ischemic and bleeding risk stratification on a combination of clinical history, symptoms, vital signs, other physical findings, 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. (Level of evidence: A)

A rapid rule-out protocol at 0 h and 3 h if high-sensitivity cardiac troponin tests are available. (Level of evidence: B)

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 to 6 hours is indicated if the first two troponin measurements are not conclusive and the clinical condition is still suggestive of ACS.(Level of evidence: B)

Continuous rhythm monitoring should be performed until the diagnosis of 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).

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 strategy which are summarized in Table 5 below. [42, 86]

Table 5.  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/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 myocardial infarction
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; GFR = glomerular filtration rate; 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. [42]


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


Administer sublingual nitroglycerin (NTG) every 5 minutes three times for continuing ischemic pain, and then assess 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)

Analgesic therapy

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-inflammatory agents (NSAIDs) (except aspirin) should not be initiated and should be discontinued because of the increased risk of a major adverse cardiac event 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 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)

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)

Administer initial therapy with nondihydropyridine CCBs with recurrent ischemia and contraindications to beta blockers in the absence of LV dysfunction, increased risk for cardiogenic shock, PR interval above 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 with recurrent ischemia after use of beta blocker and nitrates in the absence of contraindications. (Class I; level of evidence: C)

Immediate-release nifedipine is contraindicated in the absence of a beta blocker. (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 (ACEIs)

Class I

ACEIs should be started and continued indefinitely in all patients with an LVEF) below 0.40 and in those with hypertension, diabetes mellitus, or stable chronic kidney disease (CKD), unless contraindicated. (Level of evidence: A)

Angiotensin receptor blockers are recommended in patients with heart failure or MI with LVEF below 0.40 who are intolerant to ACEIs. (Level of evidence: A)

Aldosterone blockade is recommended in post–MI patients who are without significant renal dysfunction or hyperkalemia who are receiving therapeutic doses of ACEI and beta blocker and have an LVEF below 0.40, diabetes mellitus, or heart failure. (Level of evidence: A)

Antiplatelet therapy

Recommendations for initial antiplatelet/anticoagulation therapy in patients with NSTE-ACS are summarized below. [42]


Nonenteric-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 intolerance, a loading dose of clopidogrel followed by a daily maintenance dose should be administered. (Class I; level of evidence B)


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

  • Subcutaneous (SC) enoxaparin for duration of hospitalization or until percutaneous coronary intervention (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)

Dual antiplatelet therapy

In 2016, the ACC/AHA released updated guidelines on the duration of dual antiplatelet therapy (DAPT) in patients with CAD. 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 treated with DAPT are summarized below. [87] :

Class I

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

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

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

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

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 who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk, continuation of DAPT (clopidogrel, prasugrel, or ticagrelor) for longer than 12 months may be reasonable. (Level of evidence: A)

After DES implantation, patients who develop a high risk of bleeding, or are at high risk of severe bleeding complication, or develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 6 months may be reasonable. (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)

Hospital discharge and follow-up

The 2014 AHA/ACC guidelines include the following Class 1 recommendations for posthospital care [42] :

Medications required in the hospital 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 patients who have initial angina lasting more than 1 minute, NTG (1 dose sublingual or spray) if angina does not subside within 3 to 5 minutes; 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)


The 2014 AHA/ACC guidelines recommend that treatment in the acute phase of NSTE-ACS and decisions to perform stress testing, angiography, and revascularization should be similar in patients with and without diabetes mellitus. (Level of evidence: A)

The 2015 ESC guidelines offer the following recommendations [86] :

Class I

Screen all patients for diabetes and monitor blood glucose levels frequently in patients with known diabetes or admission hyperglycemia. (Level of evidence: C)

Administer the same antithrombotic treatment in diabetic and nondiabetic patients. (Level of evidence: C)

An invasive strategy is recommended over noninvasive management. (Level of evidence: A)

Monitor renal function for 2-3 days after coronary angiography or PCI in patients with baseline renal impairment or on metformin. (Level of evidence: C)

In patients undergoing PCI, new-generation DESs are recommended over BMSs. (Level of evidence: A)

In patients with stabilized multivessel CAD and an acceptable surgical risk, CABG is recommended over PCI. (Level of evidence: A)

Class IIa

Glucose-lowering therapy should be considered in ACS patients with blood glucose above 10 mmol/L (>180 mg/dL), with the target adapted to comorbidities, whereas episodes of hypoglycemia should be avoided. (Level of evidence: C)

Less stringent glucose control should be considered in patients with more advanced cardiovascular disease, older age, longer diabetes duration, and more comorbidities. (Level of evidence: C)