2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes

Authors, Journal, Affiliations, Type, DOI

• Lead authors: Sunil V. Rao, MD (Chair); Michelle L. O'Donoghue, MD, MPH (Vice Chair); Marc Ruel, MD, MPH (Vice Chair); and 27 additional writing committee members
• Journal: Circulation 2025;151:e771–e862
• Affiliations: ACC/AHA Joint Committee on Clinical Practice Guidelines, endorsed by ACEP, NAEMSP, SCAI
• Type: Clinical Practice Guideline
• DOI: 10.1161/CIR.0000000000001309
• Published: April 1, 2025
• Literature search: July 2023 – April 2024

Overview

The 2025 ACS guideline is a comprehensive single-document consolidation replacing the 2013 ACC/AHA STEMI guideline, the 2014 AHA/ACC NSTE-ACS guideline, and the 2016 DAPT focused update. It covers the full management spectrum from prehospital triage to long-term secondary prevention for type 1 AMI. Major advances include endorsement of the ticagrelor monotherapy strategy post-PCI to reduce bleeding, upgraded intracoronary imaging to Class I for complex lesions, an evidence-based algorithm for complete revascularization in multivessel disease, endorsement of the microaxial flow pump (Impella) for cardiogenic shock (DanGer-SHOCK trial, Class IIa), and incorporation of colchicine post-ACS (Class IIb). The guideline also explicitly addresses sex and racial disparities in ACS care.

Keywords

Acute coronary syndrome, angina unstable, anticoagulants, aspirin, atrial fibrillation, cardiovascular diseases, coronary artery disease, dual antiplatelet therapy, emergency medical services, fibrinolytic agents, myocardial infarction, NSTEMI, percutaneous coronary intervention, STEMI, revascularization

Key Takeaways

Definition and Classification of ACS

• ACS encompasses three related conditions along a severity continuum: (1) unstable angina, (2) NSTEMI, and (3) STEMI — caused by atherosclerotic plaque rupture or erosion with partial or complete coronary thrombosis
• Diagnosis based on clinical history, ECG interpretation, and cardiac troponin (cTn) measurement
• STEMI: ≥1 mm ST-elevation in ≥2 contiguous leads (or ≥2 mm in V2-V3 for men ≥40 y); NSTE-ACS: ST-depression or T-wave changes without persistent ST-elevation
• Universal Definition of MI Type 1 (atherothrombotic) vs Types 2–5 (other mechanisms) — this guideline focuses on Type 1

Prehospital and Initial Assessment

• 12-lead ECG within 10 minutes of first medical contact (FMC) — Class I/B-NR
• For suspected STEMI: direct EMS transport to PCI-capable hospital; FMC-to-first-device goal ≤90 minutes — Class I/B-NR
• FMC-to-device ≤120 min acceptable if ≤90 min not feasible
• Prehospital cath lab activation reduces reperfusion time and short- and long-term mortality
• Serial ECGs in non-diagnostic initial ECG; posterior leads (V7–V9) for suspected posterior STEMI
• hs-cTn preferred over conventional cTn; repeat at 1–2 h (hs-cTn) or 3–6 h (conventional assay)
• Evidence-based clinical decision pathways using delta hs-cTn can identify very low risk patients (NPV >99.5%)

Cardiac Arrest with ACS

• Resuscitated cardiac arrest + STEMI on ECG → PPCI (Class I for noncomatose or comatose with favorable features; Class IIb for comatose with unfavorable features)
• Comatose, stable, no ST-elevation after cardiac arrest: immediate angiography NOT recommended (Class III: No Benefit, Level A) — 6 RCTs showed no benefit
• Poor prognostic features for PPCI in comatose post-arrest: unwitnessed arrest, no bystander CPR, non-shockable rhythm, CPR >30 min, ROSC >30 min, pH <7.2, lactate >7 mmol/L, age >85 y, dialysis

Standard Medical Therapies

• Oxygen: Supplemental O₂ only if SpO₂ <90% (Class III: No Benefit for SpO₂ ≥90%)
• Analgesics: Nitroglycerin (SL or IV) for pain; opiates (morphine/fentanyl) may delay P2Y12 absorption — use cautiously; avoid NSAIDs
• Aspirin: Loading 162–325 mg → maintenance 75–100 mg daily — Class I/A
• P2Y12 inhibitors: Ticagrelor or prasugrel preferred over clopidogrel for PCI (Class I/B-R); clopidogrel for STEMI + fibrinolysis (Class I/A)
  • Prasugrel contraindicated with prior stroke/TIA (Class III: Harm)
  • Upstream pretreatment with clopidogrel/ticagrelor for NSTE-ACS with anticipated angiography >24 h: Class IIb
• IV cangrelor: Reasonable for PCI without prior P2Y12 loading (Class IIb/B-R)
• GP IIb/IIIa inhibitors: Adjunctive for large thrombus burden/no-reflow (Class IIa); routine use not recommended (Class III: Harm)
• Anticoagulation: UFH is standard; bivalirudin COR 1 (STEMI-PCI), COR 2b (NSTE-ACS-PCI); fondaparinux should NOT be used to support PCI (Class III: Harm — catheter thrombosis risk)
• Lipid management: High-intensity statin (Class I/A); add nonstatin agent if LDL-C ≥70 mg/dL on maximal statin (Class I/A); add nonstatin if LDL-C 55–69 mg/dL (Class IIa/B-R); ezetimibe concurrent initiation reasonable (Class IIb/B-R)
  • LDL-C lowering: no evidence of harm from very low LDL-C; do not de-escalate
  • Nonstatin options: ezetimibe, alirocumab, evolocumab, inclisiran, bempedoic acid
• Beta-blockers: For LVEF reduction post-ACS (standard GDMT)
• RAAS inhibitors: ACEi/ARB for post-ACS with reduced LVEF, HF, diabetes, hypertension

STEMI Reperfusion

• PPCI preferred over fibrinolysis when FMC-to-device ≤120 min — Class I
• FMC-to-device ≤90 min system goal; each 30-min delay → 7.5% relative increase in 1-year mortality
• Fibrinolysis when PCI not available within time window: tenecteplase/alteplase; clopidogrel loading dose (300 mg if age ≤75 y; no loading dose if >75 y)
• Post-fibrinolysis: transfer to PCI centre within 24 h; coronary angiography within 3–24 h post-fibrinolysis
• STEMI + prior fibrinolysis then PCI: ticagrelor (within 24 h of fibrinolytic) or prasugrel (>24 h post-fibrinolytic) as alternatives

NSTE-ACS Invasive Strategy

• Intermediate/high-risk NSTE-ACS: routine invasive approach during hospitalization to reduce MACE — Class I/A
• Low-risk NSTE-ACS: routine or selective invasive approach to guide revascularization — Class I/A
• Immediate invasive (<2 h): refractory angina, hemodynamic or electrical instability — Class I/C-LD
• Early invasive (within 24 h): high-risk features (GRACE score >140, rising biomarkers) — Class IIa/B-R
• Delayed angiography (48–72 h): acceptable for intermediate/low-risk without high-risk features
• Routine immediate angiography for out-of-hospital cardiac arrest without STEMI: NOT recommended (Class III: No Benefit/A)

Catheterization Laboratory Considerations

• Radial > femoral access: COR 1/A — reduces bleeding (51% relative risk reduction), vascular complications (62%), and all-cause death (24%) vs femoral (individual patient meta-analysis, 7 RCTs)
• Intracoronary imaging (IVUS or OCT): COR 1/A for left main or complex lesions — reduces target vessel failure; OCT non-inferior to IVUS; OCT superior for calcium/thrombus characterization
• Aspiration thrombectomy: Routine use NOT recommended (Class III: No Benefit/A) — no clinical benefit, possible stroke risk (3 RCTs, n=18,306)

Multivessel CAD Management

• STEMI + multivessel disease: Complete revascularization of non-infarct-related arteries recommended — Class I/A
  • Single-procedure multivessel PCI preferred over staged approach (Class IIb/B-R) — MULTISTARS AMI, BIOVASC
  • CABG reasonable for complex multivessel non-infarct artery disease (left main/LAD) — Class IIa/C-EO
  • STEMI + cardiogenic shock: culprit-only PCI — routine non-culprit PCI NOT recommended (Class III: Harm/B-R) — CULPRIT-SHOCK
• NSTE-ACS + multivessel disease: Complete revascularization recommended — Class I/B-R (FIRE trial, elderly)
  • Mode of revascularization (CABG vs multivessel PCI) based on disease complexity and comorbidities
  • Physiological assessment (FFR) of non-culprit lesions may be considered — Class IIb
  • NSTE-ACS + cardiogenic shock: culprit-only PCI — routine non-culprit PCI NOT recommended (Class III: Harm)

Cardiogenic Shock Management

• Emergency culprit vessel revascularization (PCI or CABG) regardless of time from onset — Class I/B-R
• Microaxial flow pump (Impella): Class IIa/B-R for selected STEMI + severe/refractory cardiogenic shock — DanGer-SHOCK trial (n=360): 26% reduction in all-cause mortality at 180 days (HR 0.74, NNT=8); but increased limb ischemia, bleeding, renal replacement therapy
  • Selection criteria: SCAI Stage C, D, or E; noncomatose; LVEF <45%; lactate ≥2.5 mmol/L; adequate peripheral vasculature
• IABP: Routine use NOT recommended (Class III: No Benefit/B-R) — IABP-SHOCK II
• VA-ECMO: Routine use NOT recommended (Class III: No Benefit/B-R) — ECMO-CS, ECLS-SHOCK
• MCS as bridge to surgery for mechanical complications: Class IIa/B-NR

ACS Complications

• Mechanical complications (VSR, papillary muscle rupture, free wall rupture): manage at centre with cardiac surgical expertise; MCS as bridge to surgery; surgical correction preferred
• Electrical complications:
  • ICD for LVEF ≤40% at ≥40 days post-MI and ≥90 days post-revascularization — Class I/A
  • ICD for clinically relevant VA >48 h within 40 days — Class IIa/C-EO
  • Wearable cardioverter-defibrillator (VEST): uncertain for LVEF ≤35% (Class IIb/B-R); VEST trial missed primary endpoint
  • High-degree AV block at ACS: permanent pacing indicated for persistent infranodal block — Class I/B-NR
• Post-MI pericarditis: High-dose aspirin + colchicine (0.5–0.6 mg daily × 3 months); glucocorticoids potentially harmful (impaired myocardial healing); rare in modern era (0.1–0.5%)
• LV thrombus: Anticoagulation for 3 months; DOACs non-inferior to VKA; echocardiogram recommended; anterior STEMI/LVEF <30% are highest risk

In-Hospital Management

• CICU admission for ongoing angina, hemodynamic instability, uncontrolled arrhythmias, cardiogenic shock — Class I/C-EO
• LVEF assessment before discharge — Class I/C-LD; repeat echo at 6–12 weeks if LVEF reduced
• Blood transfusion to maintain Hgb ≥10 g/dL in ACS with anemia: Class IIb/B-R — MINT trial (30-day death/MI: 16.9% restrictive vs 14.5% liberal, p=0.07; cardiac death significantly lower in liberal arm)
• Cardiac rehabilitation referral before discharge — Class I/A (reduces death, MI, hospitalization)
• Home-based CR: Class IIa/B-R (equivalent QOL and safety outcomes vs centre-based)

Discharge: DAPT Strategies

• Default: aspirin + P2Y12 inhibitor ≥12 months in patients without high bleeding risk — Class I/A
• Ticagrelor monotherapy ≥1 month post-PCI (aspirin discontinuation): Class I/A — multiple RCTs; consistent bleeding reduction without excess MACE
• PPI recommended in high GI bleeding risk patients on DAPT/OAC — Class I/A
• De-escalation (switch to clopidogrel after 1 month): Class IIb/B-R — guided or unguided
• Single antiplatelet therapy after 1 month for high bleeding risk: Class IIb/B-R
• ACS + oral anticoagulant (e.g., AF): aspirin discontinuation 1–4 weeks post-PCI + P2Y12 (clopidogrel preferred) + OAC — Class I/B-R (reduced bleeding; trials show no increase in MACE)

Secondary Prevention

• Fasting lipid panel 4–8 weeks after initiation/adjustment of lipid-lowering therapy — Class I/C-LD
• SGLT-2 inhibitors: no need to defer at discharge if indicated for HF/diabetes (dapagliflozin/empagliflozin data in post-AMI LV dysfunction — neutral on primary endpoint but empagliflozin reduced HF hospitalizations)
• Colchicine 0.5 mg daily post-ACS: Class IIb/B-R — COLCOT (32% reduction in composite MACE at 22 months); LoDoCo2 consistent; noncardiovascular death signal warrants ongoing surveillance
• Influenza vaccination: Class I/A — FLUVACS; IAMI trial (lower CV death, MI/stent thrombosis vs placebo at 1 year)

Limitations of the Document

• Literature search only through April 2024 — newer RCT data not incorporated
• Predominantly reflects US practice; international applicability varies
• Most STEMI/NSTE-ACS RCTs excluded patients with cardiogenic shock — evidence base for that population is limited
• Race/sex disparities widely acknowledged but trial diversity remains inadequate; few trials specifically designed for under-represented groups
• Multivessel PCI RCTs (STEMI) excluded patients intended for CABG — cannot extrapolate complete revascularization benefit to complex anatomy
• Colchicine benefit driven by ischemia-driven revascularization/stroke components; no CV mortality benefit confirmed; non-CV death signal in COPS trial
• DanGer-SHOCK: only 14 European specialized centres; generalizability uncertain; optimal timing/weaning of Impella not defined

Key Concepts Mentioned

• concepts/DAPT-Strategies — dual antiplatelet therapy duration and de-escalation strategies
• concepts/ASCVD-Risk-Assessment — secondary prevention LDL targets
• concepts/Dyslipidemia-Management — LDL-C targets and nonstatin agents in ACS
• concepts/Right-Heart-Catheterization — cardiogenic shock hemodynamic assessment

Key Entities Mentioned

• entities/Acute-Coronary-Syndrome — main subject of guideline
• entities/Heart-Failure — cardiogenic shock, post-MI HF, LVEF assessment
• entities/Atrial-Fibrillation — triple therapy → DAPT + OAC strategy; ACS + AF management

Wiki Pages Updated

• wiki/entities/Acute-Coronary-Syndrome.md (created)
• wiki/concepts/DAPT-Strategies.md (created)
• wiki/entities/Heart-Failure.md (updated — DanGer-SHOCK, IABP/ECMO no benefit)
• wiki/entities/Atrial-Fibrillation.md (updated — ACS + AF anticoagulation)
• wiki/concepts/Dyslipidemia-Management.md (updated — ACS LDL targets cross-link)
• wiki/wikiindex.md (updated)
• wiki/sourceindex.md (updated)