Unstable angina is a type of non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) that usually results from acute obstruction of a coronary artery without myocardial infarction. Symptoms include chest discomfort (angina pectoris) with or without dyspnea, nausea, and diaphoresis. Diagnosis is by electrocardiography (ECG) and the absence of a significant increase in cardiac troponin. Immediate treatment is with antiplatelets, anticoagulants, and nitrates, and later, with statins and beta-blockers. Coronary angiography with percutaneous intervention or coronary artery bypass surgery is often necessary. Subsequent care includes lipid management, beta-blockers, cardiac rehabilitation, risk factor management, and dual antiplatelet therapy.
Unstable angina is a type of NSTE-ACS that is defined as temporary myocardial ischemia, leading to decreased blood flow, without myocardial necrosis as evidenced by significant elevation in circulating troponin (1). It is often accompanied by ECG changes and may manifest as:
Rest angina that is prolonged (usually > 20 minutes)
New-onset angina of at least class 3 severity in the Canadian Cardiovascular Society (CCS) classification (see table )
Increasing angina, that is, previously diagnosed angina that has become distinctly more frequent, more severe, longer in duration, or lower in threshold (eg, increased by ≥ 1 CCS class or to at least CCS class 3)
Unstable angina carries an increased risk of subsequent myocardial infarction (2).
General references
1. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
2. Dakshi A, Salmon T, Collinson P, Ihsan J, Campbell M, Khand A. Unstable angina in the context of high-sensitive troponins: Still a marker of high risk? A comparison of outcomes with adjudicated type 1 myocardial infarction. Int J Cardiol. 2023;391:131226. doi:10.1016/j.ijcard.2023.131226
Symptoms and Signs of Unstable Angina
Patients have symptoms similar to those of stable angina except that the chest pain or discomfort of unstable angina usually is more intense, lasts longer, occurs spontaneously at rest, or is precipitated by lower degrees of exertion than stable angina, is progressive (crescendo) in nature, or involves any combination of these features.
Unstable angina is classified based on severity and clinical situation (see table ). Also considered are whether unstable angina occurs during treatment for chronic stable angina and whether transient changes in ST-T waves occur during angina. If angina has occurred within 48 hours and no contributory extracardiac condition is present, troponin levels may be measured with a highly sensitive assay of cardiac troponin (hs-cTn) to help estimate prognosis; a completely undetectable troponin level indicates a better prognosis than any positive level even if not meeting criteria for NSTEMI (1).
Symptoms and signs reference
1. Reichlin T, Twerenbold R, Maushart C, et al. Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays. Am Heart J. 2013;165(3):371-8.e3. doi:10.1016/j.ahj.2012.11.010
Diagnosis of Unstable Angina
Serial ECGs
Serial cardiac troponin measurements
Sometimes noninvasive risk assessment
Often coronary angiography
Evaluation begins with initial and serial ECG determinations and serial measurements of cardiac troponin to help distinguish between unstable angina and acute myocardial infarction (MI)—either non–ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI). This distinction is the center of the decision pathway for several reasons: the diagnosis determines the timing of angiography and percutaneous coronary intervention (PCI) (or other reperfusion strategy), the possibility of a selective noninvasive strategy for unstable angina in patients without certain risk factors, and because treatment with a fibrinolytic is an option for patients with STEMI but not for those with NSTE-ACS.
ECG
ECG is the most important test and should be performed as soon as possible (eg, within 10 minutes of presentation). ECG changes such as ST-segment depression, ST-segment elevation, or T-wave inversion may occur during unstable angina but are transient.
Cardiac troponin
Patients suspected of having an acute coronary syndrome (ACS), including unstable angina should have a highly sensitive assay of cardiac troponin (hs-cTn) performed on presentation and 1 to 2 hours later. If a standard troponin assay is used, measurements are performed at presentation and 3 to 6 hours later. Cardiac troponin, particularly when measured using high-sensitivity troponin tests, may be slightly increased but does not meet the criteria for myocardial infarction (above the 99th percentile of the upper reference limit).
Coronary angiography
Patients with unstable angina without clinical instability (cardiogenic shock, new or worsening heart failure symptoms, refractory ischemic symptoms, hemodynamic or electrical instability) fall into the low-risk NSTE-ACS category by definition (1). Such patients may either undergo coronary angiography before discharge or a noninvasive risk assessment with stress testing or coronary CT angiography. Those with abnormal findings on noninvasive assessment, or those with ECG findings or symptoms of ongoing ischemia, undergo angiography.
Patients presenting with clinical instability undergo immediate angiography.
Coronary angiography most often combines diagnosis with PCI (ie, angioplasty, stent placement).
Diagnosis reference
1. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
Treatment of Unstable Angina
Prehospital care: Oxygen, aspirin, and nitrates and triage to an appropriate medical center
In-hospital pharmacologic therapy: Additional antiplatelet agents, analgesics, anticoagulants, and in some cases other medications
Sometimes, reperfusion with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)
Supportive care
Post-discharge cardiac rehabilitation and chronic management of coronary artery disease
Prehospital care
Oxygen
Aspirin
Nitrates
Triage to appropriate medical center
A reliable IV route must be established, oxygen given (typically 2 L by nasal cannula) if patients have hypoxemia, and continuous ECG monitoring started. Prehospital interventions by emergency medical personnel (including ECG, chewed aspirin [160 to 325 mg], pain management with nitroglycerin) can reduce risk of mortality and complications (1). Early diagnostic data and response to treatment can help determine the need for and timing of revascularization and guide triage to the appropriate hospital.
Hospital admission
Risk-stratify patient to determine need for, timing of, and method of reperfusion (PCI or coronary artery bypass grafting [CABG])
Pharmacologic therapy with antiplatelets, anticoagulants, and other medications based on reperfusion strategy
On arrival to the emergency department, the patient's diagnosis is confirmed. Pharmacologic therapy and timing of revascularization depend on the clinical picture. In clinically unstable patients (patients with ongoing symptoms, hypotension, or sustained arrhythmias), urgent angiography with revascularization is indicated. In clinically stable patients, a selective invasive approach may be employed (see figure ).
Approach to pharmacologic therapy is discussed in Medications for Acute Coronary Syndrome, and choice of reperfusion strategy is further discussed in Revascularization for Acute Coronary Syndromes.
Approach to Unstable Angina
a Use morphine or fentanyl judiciously if nitroglycerin is contraindicated or if the patient has symptoms despite nitroglycerin therapy; they may attenuate the effect of P2Y12 inhibitors. |
b See Antiplatelet Agents for more detail. |
c Based on risk scores, troponin, symptoms, and ECG changes. |
d Unstable patients include those with cardiogenic shock, new or worsening heart failure symptoms, refractory ischemic symptoms, and hemodynamic or electrical instability. |
e CABG may be preferred to PCI for patients with the following: High complexity coronary disease that involves the left main coronary artery, diabetes and multivessel disease involving the left anterior descending artery, multivessel or diffuse disease, or severe left ventricular dysfunction with multivessel or complex left main disease. |
ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; CABG = coronary artery bypass grafting; CCTA = coronary CT angiography; NSTE–ACS = non–ST-segment elevation–acute coronary syndrome; MINOCA = myocardial infarction with non-obstructive coronary arteries; PCI = percutaneous intervention; SL = sublingual. |
Data from Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309. |
Pharmacologic treatment of unstable angina
All patients should be given antiplatelet agents, anticoagulants, and if chest pain is present, antianginals. The specific medications used depend on the reperfusion strategy and other factors; medication selection and use are discussed in Medications for Acute Coronary Syndromes. Other medications, such as beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), and statins, should be initiated during admission (see Post-ACS Treatment and Rehabilitation and the table ).
Patients with unstable angina should be given the following (unless contraindicated):
Antiplatelet agents: Aspirin and prasugrel, ticagrelor, or clopidogrel
Anticoagulants: A heparin (unfractionated or low molecular weight heparin) or bivalirudin
Sometimes a glycoprotein IIb/IIIa inhibitor when PCI is performed
Antianginal therapy, usually nitroglycerin
Beta-blocker
Angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB)
Statin and sometimes additional lipid-lowering agents
Sometimes mineralocorticoid receptor antagonists
All patients are given aspirin 160 to 325 mg (not enteric-coated), if not contraindicated. Chewing the first dose before swallowing quickens absorption. Aspirin reduces short-term and long-term mortality risk (2). In patients undergoing PCI, a loading dose of prasugrel (60 mg orally once), ticagrelor (180 mg orally once), or clopidogrel (300 to 600 mg orally once) is recommended to reduce ischemic events (3). For urgent PCI, prasugrel and ticagrelor are more rapid in onset and may be preferred. IV cangrelor may also be used during PCI to reduce ischemic events in patients who are P2Y12-inhibitor naive (4).
Either a low molecular weight heparin (LMWH), unfractionated heparin, or bivalirudin is given routinely to patients with unstable angina unless contraindicated (eg, by active bleeding) (5). Unfractionated heparin is more complicated to use because it requires frequent (every 6 hours) dosing adjustments to achieve target activated partial thromboplastin time (aPTT). The LMWHs have better bioavailability, are given by simple weight-based dose without monitoring aPTT and dose titration, and have lower risk of heparin-induced thrombocytopenia; they are recommended when an early invasive strategy is not planned. Bivalirudin is recommended for patients with a known or suspected history of heparin-induced thrombocytopenia who are undergoing PCI.
Consider a glycoprotein IIb/IIIa inhibitor during (or sometimes before) PCI for patients with high-risk lesions (eg, high thrombus burden, no reflow). Abciximab, tirofiban, and eptifibatide appear to have equivalent efficacy, and the choice of agent should depend on other factors (eg, cost, availability, familiarity) (35).
Chest pain can be treated with sublingual or intravenous nitroglycerin, or sometimes morphine or fentanyl (5). Nitroglycerin is preferable to opioids, which should be used judiciously (eg, if a patient has a contraindication to nitroglycerin or is in pain despite maximal nitroglycerin therapy). Nitroglycerin is initially given sublingually, followed by continuous IV drip if needed. Morphine, given 2 to 4 mg IV, repeated every 15 minutes as needed, is highly effective but can depress respiration, can reduce myocardial contractility, and is a potent venous vasodilator. Evidence also suggests that morphine and fentanyl interfere with some P2Y12 receptor inhibitor activity (6, 7, 8). A large retrospective trial also showed that morphine may increase mortality in patients with acute myocardial infarction (7, 8). Hypotension and bradycardia may also occur secondary to morphine use, but these complications can usually be overcome by prompt elevation of the lower extremities.
Post-acute pharmacologic treatment
Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (eg, ticagrelor, clopidogrel) for up to 1 year is recommended (5, 9, 10). A proton pump inhibitor should be given with dual antiplatelet therapy. If PCI was performed, options for tapering to monotherapy sooner than 12 months, with aspirin or a P2Y12 inhibitor, are discussed in more detail under Treatment of Acute Coronary Syndromes and Medications for Acute Coronary Syndromes.
Standard therapy for all patients with acute coronary syndromes includes beta-blockers, ACE inhibitors or ARBs, and statins (5). Beta-blockers are recommended unless contraindicated (eg, by bradycardia, heart block, hypotension, or asthma), especially for high-risk patients. Beta-blockers reduce heart rate, arterial pressure, and contractility, thereby reducing cardiac workload and oxygen demand. However, beta-blockers may have limited benefit in patients with preserved left ventricular ejection fraction (11, 12). ACE inhibitors or ARBs may provide long-term cardioprotection by improving endothelial function (13), particularly in patients with heart failure, hypertension, diabetes, or chronic kidney disease. Statins are also standard therapy regardless of lipid levels and should be continued indefinitely, with the addition of other lipid-lowering medications as needed.
Mineralocorticoid receptor antagonists (spironolactone or eplerenone) are indicated for patients with left ventricular dysfunction and either heart failure symptoms or diabetes following ACS, to reduce morbidity and mortality (5, 14).
Reperfusion therapy in unstable angina
In patients with unstable angina, angiography is often performed prior to discharge if the patient is stable or immediately in unstable patients (with cardiogenic shock, new or worsening heart failure symptoms, refractory ischemic symptoms, hemodynamic or electrical instability). Angiographic findings help determine whether PCI or coronary artery bypass grafting (CABG) is indicated. Choice of reperfusion strategy is further discussed in Revascularization for Acute Coronary Syndromes.
Fibrinolytic drugs, which can be helpful in patients with STEMI without access to immediate angiography and PCI, are not indicated for patients with unstable angina (5).
Pearls & Pitfalls
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Rehabilitation and post-discharge treatment
Functional evaluation
Cardiac rehabilitation
Changes in lifestyle: Regular exercise, diet modification, weight loss, smoking cessation
Post-acute pharmacologic therapy is discussed above.
Patients who did not have coronary angiography during admission, have no high-risk features (eg, heart failure, recurrent angina, ventricular tachycardia or ventricular fibrillation after 24 hours, mechanical complications such as new murmurs, shock), and have an ejection fraction > 40% usually should have stress testing of some sort before or shortly after discharge.
Supervised cardiac rehabilitation programs based in clinics or hospitals or home-based programs are recommended for all patients after acute coronary syndromes (5) and decrease cardiovascular mortality after revascularization (15).
The acute illness and treatment of unstable angina should serve as a catalyst for discussion of modifiable cardiovascular risk factors. Evaluating the patient’s physical and emotional status and discussing them with the patient, advising about lifestyle (eg, smoking, diet, work and play habits, exercise), and aggressively managing risk factors may improve prognosis.
Treatment references
1. Nakayama N, Yamamoto T, Kikuchi M, et al: Prehospital Administration of Aspirin and Nitroglycerin for Patients With Suspected Acute Coronary Syndrome—A Systematic Review. Circ Rep 4(10):449–457, 2022. doi:10.1253/circrep.CR-22-0060
2. Antithrombotic Trialists' Collaboration: Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients [published correction appears in BMJ 2002 Jan 19;324(7330):141]. BMJ 324(7329):71–86, 2002. doi:10.1136/bmj.324.7329.71
3. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(3):e18-e114. doi:10.1161/CIR.0000000000001038
4. Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303-1313. doi:10.1056/NEJMoa1300815
5. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
6. Ibrahim K, Shah R, Goli RR, et al. Fentanyl Delays the Platelet Inhibition Effects of Oral Ticagrelor: Full Report of the PACIFY Randomized Clinical Trial. Thromb Haemost. 2018;118(8):1409-1418. doi:10.1055/s-0038-1666862
7. Kubica J, Adamski P, Ostrowska M, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016;37(3):245-252. doi: 10.1093/eurheartj/ehv547
8. Meine TJ, Roe MT, Chen AY, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. Am Heart J. 2005;149(6):1043-1049. doi 10.1016/j.ahj.2005.02.010
9. Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227-3337. doi:10.1093/eurheartj/ehab484
10. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057. doi:10.1056/NEJMoa0904327
11. Ibanez B, Latini R, Rossello X, et al. Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction. N Engl J Med. 2025;393(19):1889-1900. doi:10.1056/NEJMoa2504735
12. Munkhaugen J, Kristensen AMD, Halvorsen S, et al. Beta-Blockers after Myocardial Infarction in Patients without Heart Failure. N Engl J Med. 2025;393(19):1901-1911. doi:10.1056/NEJMoa2505985
13. Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-153. doi:10.1056/NEJM200001203420301
14. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-3826. doi:10.1093/eurheartj/ehad191
15. Dibben G, Faulkner J, Oldridge N, et al. Exercise-based cardiac rehabilitation for coronary heart disease. Cochrane Database Syst Rev. 2021;11(11):CD001800. doi:10.1002/14651858.CD001800.pub4
Prognosis for Unstable Angina
Prognosis after an episode of unstable angina depends upon the extent and number of coronary arteries involved as well as other factors such as age, symptom severity, degree of ST-segment deviation, and pre-existing risk of coronary artery disease (1, 2). In addition to estimating prognosis, calculation of risk using the TIMI or GRACE scores can guide the decision to revascularize versus taking a more conservative approach in unstable angina (3).
Studies using the current definition of unstable angina with a high-sensitivity cardiac troponin assay report 1-year myocardial infarction rate of 1.4 to 1.9% and a 1-year overall mortality rate of 0.6 to 2.2% (4, 5).
Prognosis references
1. Figueras J, Domingo E, Hermosilla E. Long-term prognosis of clinical variables, coronary reserve and extent of coronary disease in patients with a first episode of unstable angina. Int J Cardiol. 2005;98(1):27-34. doi:10.1016/j.ijcard.2003.08.005
2. Sabatine MS, Antman EM. The thrombolysis in myocardial infarction risk score in unstable angina/non-ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2003;41(4 Suppl S):89S-95S. doi:10.1016/s0735-1097(02)03019-x
3. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
4. Dakshi A, Salmon T, Collinson P, Ihsan J, Campbell M, Khand A. Unstable angina in the context of high-sensitive troponins: Still a marker of high risk? A comparison of outcomes with adjudicated type 1 myocardial infarction. Int J Cardiol. 2023;391:131226. doi:10.1016/j.ijcard.2023.131226
5. Paiva LMV, Vieira MJ, Simões M, Ferreira MJ, Gonçalves L. Unstable Angina Risk Stratification Using High-Sensitivity Cardiac Troponin and Coronary Angiography. Am J Cardiol. 2024;221:1-8. doi:10.1016/j.amjcard.2024.03.034
Key Points
Unstable angina is defined as myocardial ischemia associated with reduced coronary flow, but without myonecrosis.
Symptoms of unstable angina include new or worsening chest pain or chest pain occurring at rest.
Diagnosis is based on symptoms, serial ECG findings and the absence of a significant elevation in cardiac troponin.
Immediate treatment includes oxygen, antianginals, antiplatelets, and anticoagulants.
For patients with refractory symptoms, shock, hypotension, or sustained arrhythmias, do immediate angiography.
For stable patients, do angiography during hospitalization, or consider non-invasive risk stratification.
Following recovery, initiate or continue antiplatelet agents, beta-blockers, ACE inhibitors or angiotensin II receptor blockers, and statins.
Initiate cardiac rehabilitation and aggressively manage risk factors.
Drug Information for the Topic
