Quick Reference

RxDrug of choiceTicagrelor 180 mg load then 90 mg BID (or prasugrel 60 mg load then 10 mg daily) plus aspirin 81 mg daily (DAPT).

AltAlternativesClopidogrel 300-600 mg load then 75 mg daily (for high bleeding risk, age ≥70 years, or contraindication to ticagrelor/prasugrel).

⊘AvoidPrasugrel with prior stroke or TIA; NSAIDs for pain; routine oxygen in normoxic patients.

DxTest of choice12-lead ECG within 10 minutes of presentation; high-sensitivity cardiac troponin (hs-cTn) at 0 and 1 hour (ESC 0h/1h algorithm).

ScKey scoreGRACE 2.0 risk score (8 variables: age, heart rate, SBP, Killip class, creatinine, cardiac arrest, ST deviation, elevated biomarkers). Score >140 = high risk (early invasive strategy).

→When to referImmediate cardiology consultation for STEMI, cardiogenic shock, mechanical complications (free wall rupture, VSD, papillary muscle rupture), refractory arrhythmias, or need for complex revascularization (multivessel disease, left main disease).

Time is myocardium. ECG and hs-cTn within minutes guide reperfusion; complete revascularization and optimal GDMT (DAPT, statin, beta-blocker, ACEi/ARB) reduce long-term mortality.

Acute coronary syndrome (ACS) encompasses unstable angina, NSTEMI, and STEMI, all arising from acute myocardial ischemia due to abrupt reduction in coronary blood flow. Immediate ECG and high-sensitivity troponin distinguish STEMI (requiring urgent reperfusion) from NSTE-ACS. Management hinges on prompt antiplatelet therapy, revascularization, and long-term risk factor control to reduce mortality and recurrent events.

Overview and Recommendations

Background

•ACS is a spectrum of acute myocardial ischemia caused by abrupt reduction in coronary blood flow, classically due to atherosclerotic plaque rupture or erosion with superimposed thrombosis. It affects approximately 1 million individuals annually in the United States and accounts for a global incidence of 7-14 per 1000 person-years in high-income countries.
•The 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline emphasizes precise classification at the point of care, which drives downstream decisions: emergent reperfusion for STEMI, risk-stratified invasive management for NSTE-ACS, and tailored antithrombotic strategy. Untreated, 30-day mortality for STEMI approaches 30%, driven largely by cardiogenic shock and ventricular arrhythmias.
•Functional classification divides ACS by ST-segment elevation on ECG (STEMI indicates transmural ischemia and mandates immediate reperfusion; NSTE-ACS is subendocardial or patchy ischemia). Anatomic classification identifies the culprit coronary artery and lesion morphology (plaque rupture ~75%, plaque erosion ~30%, calcified nodules rare). Etiologic classification distinguishes Type 1 MI (atherothrombosis) from Type 2 MI (supply-demand mismatch without acute atherothrombosis).
•The paradigm shift in management has been driven by landmark trials: PARADIGM-HF (2014) and DAPA-HF (2019) cemented four-pillar GDMT for HFrEF, while PLATO (2009) and TRITON-TIMI 38 (2007) established ticagrelor/prasugrel over clopidogrel. The 2025 guideline further refines risk-directed DAPT duration, complete revascularization, and anti-inflammatory therapy with colchicine.

Evaluation

•Suspect ACS in any patient with substernal pressure, squeezing, or heaviness radiating to the left arm, neck, or jaw, especially if provoked by exertion and relieved by rest or nitroglycerin. The classic description has a positive likelihood ratio >4.5, but atypical presentations (isolated dyspnea, epigastric pain, fatigue, syncope) are common in women, the elderly, and patients with diabetes, up to 33% of these groups have no chest pain at all.
•Ask about onset, duration, and quality of pain; associated symptoms (diaphoresis, nausea, dyspnea, palpitations); and provoking factors (exertion, emotional stress, infection). Also inquire about traditional risk factors (smoking, hypertension, diabetes, dyslipidemia) and prior CAD (MI, PCI, CABG).
•Examine vital signs: hypotension (SBP <90 mmHg) or tachycardia may indicate cardiogenic shock; a shock index (HR/SBP) >0.7 predicts increased mortality (OR 4.82). Fever suggests myocarditis, pericarditis, or Kounis syndrome, not uncomplicated ACS.
•Auscultate for a third heart sound (S3) and crackles indicating elevated left atrial pressure (Killip Class II-III); a new mitral regurgitation murmur suggests papillary muscle dysfunction; jugular venous distention with clear lungs raises concern for right ventricular infarction.
•Order a 12-lead ECG within 10 minutes of first medical contact. ST-segment elevation ≥1 mm in two contiguous limb leads or ≥2 mm in two contiguous precordial leads defines STEMI. New left bundle branch block is a STEMI equivalent. ST depression or T-wave inversion suggests NSTEMI/UA. A normal ECG does not exclude ACS, up to 5% of patients with acute MI have a normal ECG.
•Measure high-sensitivity cardiac troponin (hs-cTn) at presentation (0 hour). A single hs-cTn below the limit of detection (e.g., <5 ng/L for hs-cTnI) has a negative predictive value >99% for 30-day MACE, allowing safe early discharge in low-risk patients (HEART score ≤3).
•If the initial hs-cTn is elevated or the patient is intermediate/high-risk, repeat hs-cTn at 1 hour (or 2-3 hours if using a 0/2- or 0/3-hour protocol). Apply the ESC 0-hour/1-hour algorithm: rule-out if 0h hs-cTnT <12 ng/L with Δ <3 ng/L (or hs-cTnI <5 ng/L with Δ <2 ng/L); rule-in if 0h hs-cTnT ≥52 ng/L or Δ ≥5 ng/L (or hs-cTnI ≥64 ng/L or Δ ≥6 ng/L); all others fall into an observe zone requiring further testing.
•Diagnostic criteria for acute MI: rise and/or fall of cardiac troponin with at least one value >99th percentile URL, plus ischemic ECG changes, symptoms, or imaging evidence of new wall motion abnormality. Unstable angina is diagnosed with ischemic symptoms and dynamic ECG changes but no troponin elevation.
•In low-to-intermediate-risk emergency department patients, coronary computed tomographic angiography (CCTA) has a NPV of 99% for ACS when no stenosis ≥50% is found and can reduce length of stay.
•Consider alternative diagnoses: Takotsubo syndrome (apical ballooning on echo, emotional trigger), myocarditis (viral prodrome, diffuse ST elevation, cardiac MRI with late gadolinium enhancement), pulmonary embolism (S1Q3T3 pattern, D-dimer, CT pulmonary angiography), SCAD (young women, intramural hematoma on angiography), aortic dissection (tearing chest pain radiating to back, pulse deficits), and Kounis syndrome (allergic trigger with chest pain and troponin elevation).
•Risk stratify all patients with confirmed NSTEMI or UA using the GRACE 2.0 score (8 variables: age, heart rate, SBP, Killip class, creatinine, cardiac arrest, ST deviation, elevated biomarkers). GRACE >140 defines high-risk patients who derive the greatest absolute benefit from an early invasive strategy (angiography within 24 hours).
•Assess bleeding risk with the CRUSADE or PRECISE-DAPT score to guide antiplatelet therapy duration and intensity. In older adults (≥75 years), supplement GRACE with a frailty assessment (e.g., Clinical Frailty Scale) for additional prognostic information.

Management

•Immediately stabilize: oxygen only if SpO₂ <90% (not routine); chewed aspirin 162-325 mg; nitroglycerin 0.4 mg sublingual every 5 minutes for ongoing chest pain (up to 3 doses) unless SBP <90 mmHg or suspected right ventricular infarction.
•For STEMI, activate the catheterization laboratory for primary PCI with door-to-balloon time ≤90 minutes. If PCI cannot be performed within 120 minutes, administer fibrinolytic therapy (tenecteplase 30-50 mg IV bolus based on weight, or alteplase 15 mg IV bolus → 0.75 mg/kg over 30 min → 0.5 mg/kg over 60 min) within 30 minutes of arrival, then transfer to a PCI-capable center for routine angiography within 2-24 hours (pharmaco-invasive approach).
•Initiate dual antiplatelet therapy as soon as possible: ticagrelor 180 mg oral loading dose (then 90 mg BID) or prasugrel 60 mg oral loading dose (then 10 mg daily), Class 1, Level B-R. Prasugrel is contraindicated if prior stroke or TIA. Clopidogrel 300-600 mg loading (then 75 mg daily) is reserved for patients with high bleeding risk, age ≥70 years, or contraindications to ticagrelor/prasugrel.
•Administer anticoagulation: unfractionated heparin (UFH) 70 U/kg IV bolus (max 4,000 U) with target ACT 250-300 seconds if PCI planned, OR enoxaparin 1 mg/kg SC every 12 hours (0.75 mg/kg if age ≥75 years) for conservatively managed patients. Bivalirudin is an alternative for heparin-induced thrombocytopenia.
•For high-risk NSTE-ACS (dynamic ECG changes, elevated troponin, hemodynamic instability, ventricular arrhythmias, GRACE >140), proceed with early invasive strategy (angiography within 24 hours). For intermediate-risk patients, angiography within 48-72 hours is reasonable. Conservative management is reserved for low-risk patients without recurrent ischemia.
•Perform culprit-only PCI for most patients. For multivessel disease, complete revascularization (during index procedure or staged within 45 days) reduces MACE (HR 0.71, 95% CI 0.55-0.91; NNT = 18). In patients with left main disease and SYNTAX score ≤22, PCI is a Class IIa alternative to CABG.
•Use intravascular imaging (IVUS or OCT) to guide complex PCI; IVUS-ACS trial showed reduced cardiac death, target-vessel MI, or ischemia-driven revascularization at 1 year (4.7% vs 7.1%; HR 0.65, 95% CI 0.47-0.91; NNT = 42).
•Initiate high-intensity statin immediately: atorvastatin 80 mg daily or rosuvastatin 40 mg daily regardless of baseline LDL-C, aiming for ≥50% reduction and LDL-C <55 mg/dL (1.4 mmol/L). Add ezetimibe 10 mg daily for patients with LDL-C ≥70 mg/dL at presentation. If target not achieved on maximally tolerated statin + ezetimibe, add a PCSK9 inhibitor (alirocumab 75-150 mg SC q2 weeks or evolocumab 140 mg SC q2 weeks).
•Start beta-blockade within the first 24 hours in patients without heart failure or cardiogenic shock: metoprolol tartrate 25-50 mg every 6 hours OR carvedilol 6.25 mg twice daily. Continue for 3 years if LVEF >40% (Class IIa); continue indefinitely if LVEF ≤40% or heart failure (Class I).
•Initiate an ACE inhibitor (e.g., ramipril 2.5 mg daily) or ARB (e.g., valsartan 40 mg twice daily) within 24 hours for patients with anterior STEMI, heart failure, or LVEF ≤40% (Class I). Titrate to target doses as tolerated.
•Add a mineralocorticoid receptor antagonist (spironolactone 12.5-25 mg daily or eplerenone 25-50 mg daily) if LVEF ≤40% and heart failure or diabetes, with careful monitoring of potassium and renal function (Class I).
•For patients with high ischemic risk (multivessel disease, diabetes, prior stent thrombosis) and low bleeding risk, extend DAPT with ticagrelor 60 mg BID for up to 3 years after the first 12 months (PEGASUS-TIMI 54: HR 0.84, 95% CI 0.74-0.95; NNT = 56 over 3 years). For high bleeding risk patients, abbreviate DAPT to 1-3 months followed by P2Y12 inhibitor monotherapy.
•Consider low-dose colchicine 0.5 mg daily in patients with residual inflammatory risk (hs-CRP ≥2 mg/L) despite statin therapy (Class IIb).
•Prescribe annual influenza vaccination for all ACS patients (Class I). A meta-analysis showed vaccination reduced cardiovascular events (RR 0.64, 95% CI 0.48-0.86; NNT = 58).
•Monitor for complications: cardiogenic shock (5-10% of STEMI; manage with revascularization ± mechanical circulatory support), sustained VT/VF (defibrillation, IV amiodarone), major bleeding (radial access, age/weight-adjusted anticoagulation, PPI for GI protection), contrast-associated AKI (isotonic hydration, minimize contrast volume).
•What NOT to do: do not routinely give oxygen to normoxic patients; do not use NSAIDs for pain; do not hold antiplatelet therapy for planned CABG beyond recommended washout (ticagrelor 3-5 days, clopidogrel 5 days, aspirin continue); do not perform non-culprit PCI of a totally occluded artery without ongoing ischemia; do not routinely stress test at 12 months post-PCI in asymptomatic patients.
•Discharge criteria: hemodynamically stable, no recurrent ischemia for ≥12 hours, LVEF assessed, GDMT initiated and tolerated, follow-up arranged within 2 weeks. Same-day discharge may be considered only for low-risk, uncomplicated, transradial PCI patients (meta-analysis found no difference in death, MI, or TLR vs overnight observation).

Board Review — High Yield

•STEMI vs NSTEMI, STEMI: ST elevation ≥1 mm in limb leads or ≥2 mm in precordial leads, transmural ischemia, requires immediate reperfusion. NSTEMI: troponin elevation without ST elevation, subendocardial necrosis, urgent invasive strategy.
•ESC 0h/1h algorithm, Rule-out: hs-cTnT <12 ng/L and Δ <3 ng/L (or hs-cTnI <5 ng/L and Δ <2 ng/L). Rule-in: hs-cTnT ≥52 ng/L or Δ ≥5 ng/L (or hs-cTnI ≥64 ng/L or Δ ≥6 ng/L).
•GRACE >140, High risk for in-hospital mortality; benefit from early invasive strategy (angiography within 24 hours).
•P2Y12 inhibitor choice, Ticagrelor or prasugrel preferred over clopidogrel (Class I). Prasugrel contraindicated with prior stroke/TIA. Clopidogrel for high bleeding risk or age ≥70 (POPular AGE trial).
•Complete revascularization, In multivessel disease, complete revascularization (index or staged within 45 days) reduces CV death/MI (HR 0.71; NNT = 18). IVUS-guided PCI reduces target-vessel failure (HR 0.65; NNT = 42).
•High-intensity statin, Atorvastatin 80 mg daily or rosuvastatin 40 mg daily, aiming for LDL-C <55 mg/dL (1.4 mmol/L). Add ezetimibe if LDL-C ≥70 mg/dL at presentation.
•Extended DAPT, Consider ticagrelor 60 mg BID after 12 months in high ischemic risk/low bleeding risk patients (PEGASUS-TIMI 54).
•Colchicine, Low-dose (0.5 mg daily) for residual inflammatory risk (hs-CRP ≥2 mg/L) after statin (Class IIb).
•Annual influenza vaccine, Reduces CV events by 36% (RR 0.64; NNT = 58); strongly recommended in all ACS patients.
•Radial access over femoral, Reduces major bleeding (NNT = 13) and is preferred for PCI.

Deep Dive — Evidence Details

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Acute Coronary Syndrome