Summary

Comprehensive 2025 multisociety guideline for management of acute coronary syndromes (STEMI, NSTEMI, unstable angina), replacing the 2013 STEMI, 2014 NSTE-ACS, 2015 PPCI focused update, and 2016 DAPT duration focused update guidelines. Major updates include preference for ticagrelor/prasugrel over clopidogrel, ticagrelor monotherapy after 1 month of DAPT in select patients, more aggressive LDL-C targets (<70 mg/dL, intensify if 55–<70), complete revascularization (preferably single-setting) in STEMI, routine radial access, intracoronary imaging for complex PCI, microaxial flow pump for selected AMI cardiogenic shock, and a more liberal transfusion threshold (Hb ~10 g/dL) in ACS with anemia.

Key Recommendations

Give DAPT (aspirin + ticagrelor or prasugrel preferred over clopidogrel) for at least 12 months in ACS patients not at high bleeding risk.
In patients who tolerate ticagrelor-based DAPT, transition to ticagrelor monotherapy ≥1 month after PCI to reduce bleeding without increasing ischemic events.
Discontinue aspirin 1–4 weeks after PCI in ACS patients requiring long-term anticoagulation, continuing P2Y12 inhibitor (preferably clopidogrel) plus a DOAC.
Start high-intensity statin in all ACS patients; add ezetimibe and/or PCSK9 inhibitor/inclisiran/bempedoic acid if LDL-C ≥70 mg/dL on maximally tolerated statin, and consider further intensification if LDL-C 55–<70 mg/dL.
Pursue routine invasive strategy in intermediate/high-risk NSTE-ACS; immediate (<2 h) angiography for hemodynamic/electrical instability, refractory angina, or acute HF.
Primary PCI is preferred reperfusion for STEMI with FMC-to-device ≤90 min (≤120 min for transfers); give fibrinolytic therapy if PPCI cannot be achieved within 120 min and symptoms <12 hours, followed by transfer for routine angiography 2–24 h later.
Use radial access over femoral for PCI in ACS to reduce bleeding, vascular complications, and mortality.
Use intracoronary imaging (IVUS or OCT) to guide PCI in complex coronary lesions.
Perform complete revascularization in stable STEMI or NSTE-ACS with multivessel disease (preferably single-setting in STEMI); culprit-only PCI in cardiogenic shock.
Consider microaxial flow pump in selected STEMI patients with cardiogenic shock (SCAI stages C–E, non-comatose, adequate vascular access) to reduce mortality.
Target hemoglobin ~10 g/dL with red blood cell transfusion in ACS patients with anemia who are not actively bleeding.
Refer all eligible ACS patients to cardiac rehabilitation (home-based acceptable if center-based not feasible) and obtain fasting lipid panel 4–8 weeks after starting or adjusting lipid-lowering therapy.

Thresholds & Doses

Aspirin loading dose 162–325 mg, then 75–100 mg daily maintenance (≤100 mg/d when combined with ticagrelor).
Clopidogrel: 300–600 mg load, 75 mg daily; with fibrinolytic and age >75 y use 75 mg daily without loading dose.
Prasugrel: 60 mg load, 10 mg daily (5 mg if <60 kg or ≥75 y); contraindicated with prior stroke/TIA.
Ticagrelor: 180 mg load, 90 mg twice daily.
UFH: 60 IU/kg bolus (max 4000), 12 IU/kg/h infusion (max 1000/h), aPTT 60–80 s; PCI ACT target 250–300 s.
Bivalirudin for PPCI: 0.75 mg/kg bolus, 1.75 mg/kg/h infusion, continue 1.75 mg/kg/h for 2–4 h post-PCI.
Enoxaparin: 1 mg/kg SC q12h (1 mg/kg daily if CrCl <30); with fibrinolytic age ≥75 use 0.75 mg/kg SC q12h, no bolus.
Fondaparinux: 2.5 mg SC daily; contraindicated CrCl <30; do not use as sole anticoagulant for PCI.
STEMI ECG criteria: new ST-elevation ≥1 mm in ≥2 contiguous leads; in V2–V3 ≥2 mm men ≥40 y, ≥2.5 mm men <40 y, ≥1.5 mm women.
FMC-to-device time ≤90 min for PPCI at PCI-capable hospital, ≤120 min for transfer; goal ECG within 10 min of presentation.
Fibrinolysis indicated if symptoms <12 h and PPCI unavailable within 120 min; tenecteplase weight-based bolus (30–50 mg).
High-intensity statin: atorvastatin 40–80 mg or rosuvastatin 20–40 mg (≥50% LDL-C reduction).
LDL-C target after ACS: add nonstatin therapy if ≥70 mg/dL; reasonable to further intensify if 55–<70 mg/dL.
Transfusion target hemoglobin ~10 g/dL in ACS with anemia (MINT trial threshold).
Colchicine 0.5–0.6 mg once or twice daily after MI; contraindicated if CrCl <15 mL/min.
Eplerenone indicated post-MI if LVEF ≤40% with HF or diabetes; avoid if Cr >2.5 mg/dL or K >5.0 mmol/L.
ICD for primary prevention: LVEF ≤30% (any NYHA), 31–35% (NYHA II–III), or ≤40% with inducible VT; ≥40 days post-MI; survival ≥1 year.
Microaxial flow pump in STEMI cardiogenic shock: 26% relative reduction in 180-day mortality (DanGer-SHOCK), NNT=8.
Aspirin 500–1000 mg q6–8h plus colchicine 0.5–0.6 mg daily for 3 months for persistent post-MI pericarditis.
Anticoagulation for LV thrombus typically 3 months, then reimage.

Citations

Top Take-Home Messages — overarching DAPT, lipid, invasive, revascularization, MCS, transfusion, and discharge recommendations
Section 4.3.2 (Table 7) — oral P2Y12 inhibitor dosing and choice (ticagrelor/prasugrel preferred over clopidogrel)
Section 4.4 (Table 10) — parenteral anticoagulation dosing for UFH, bivalirudin, enoxaparin, fondaparinux
Section 4.5 (Figure 5, Tables 11–12) — high-intensity statin and nonstatin lipid-lowering therapy thresholds
Section 5.2.1 — Primary PCI timing goals (≤90 min FMC-to-device; ≤120 min transfer)
Section 6.1 (Figures 7–8) — Routine vs selective invasive strategy in NSTE-ACS
Section 7.4.1 — Complete revascularization in STEMI with multivessel disease
Section 8.2 — Microaxial flow pump in AMI cardiogenic shock (DanGer-SHOCK)
Section 10.2 — Liberal transfusion strategy targeting Hb ~10 g/dL (MINT trial)
Section 11.1 (Figure 11, Table 22) — DAPT strategies including ticagrelor monotherapy after 1 month
Section 9.2 (Table 17) — ICD indications for primary prevention post-MI
Section 11.4 — Chronic colchicine after MI (COLCOT, LoDoCo2)