Unstable Angina Guidelines

Updated: May 07, 2019
  • Author: Walter Tan, MD, MS; Chief Editor: Eric H Yang, MD  more...
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Guidelines Summary

Guidelines for the management of non–ST-elevation acute coronary syndromes (NSTE-ACS) have been issued by:

  • American Heart Association/American College of Cardiology (AHA/ACC)
  • European Society of Cardiology (ESC)

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 release its guidelines which define unstable angina as "myocardial ischemia at rest or minimal exertion in the absence of cardiomyocyte necrosis." [84]


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 [84]

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 managment stategy which are summarized in Table 5 below. [42, 84]

Table 5.  Recommendations for Selection of Preferred Managment 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; evel 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. [85] :

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 [84] :

Class I

Screen all patients for diabetes and monitor blood glucose levels frequently in patients with known diabetes or admission hyperglycaemia. (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 stabilised 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)