Board-level quick read · Cardiology
Acute Coronary Syndrome
ACC/AHA/ACEP/NAEMSP/SCAI 2025 · reviewed 2026-09-08
Personal study digest for IM board review. Recommendations are from the cited guideline; the “What’s changed” section is reviewer synthesis of newer evidence, each claim cited. Not a substitute for the full guideline.
In one line
ACS splits into STEMI (ST elevation or new LBBB → emergent reperfusion) and NSTE-ACS (unstable angina or NSTEMI → risk-stratify, then invasive strategy for intermediate-to-high risk). The 2025 guideline upgrades radial access, intracoronary imaging, multivessel PCI in stable STEMI, and microaxial flow pumps (Impella) in cardiogenic shock, while downgrading IABP and VA-ECMO.
When to suspect / diagnose
- STEMI: Chest pain + ST elevation ≥1 mm in ≥2 contiguous leads (or ≥2 mm in V2–V3), new LBBB, or posterior MI pattern. Activate the cath lab.
- NSTE-ACS: Ischemic symptoms + ST depression, transient ST elevation, T-wave inversion, or positive high-sensitivity troponin. Normal ECG does not exclude it.
- Serial troponin (high-sensitivity preferred) at 0 and 1–3 h; a rise-and-fall pattern with ≥1 value above the 99th percentile confirms myocardial injury.1
- 12-lead ECG within 10 minutes of first medical contact. COR 1
Workup
- Risk scores: HEART score for chest-pain triage (low ≤3 → early discharge pathway). GRACE score for in-hospital prognosis and invasive-strategy timing (>140 = high risk → early angiography ≤24 h). COR 1
- Echocardiography: LVEF assessment before discharge. COR 1
- CT coronary angiography: reasonable for low-to-intermediate risk NSTE-ACS when diagnosis uncertain. COR 2a
Empiric & definitive therapy
Antiplatelet therapy
| Agent | Loading dose | Maintenance | Strength |
|---|---|---|---|
| Aspirin (all ACS) | 162–325 mg chewed | 81 mg daily | COR 1 |
| Ticagrelor (preferred P2Y12) | 180 mg PO | 90 mg BID | COR 1 |
| Prasugrel (PCI, no prior stroke/TIA) | 60 mg PO | 10 mg daily (5 mg if <60 kg) | COR 1 |
| Clopidogrel (if ticagrelor/prasugrel not tolerated) | 300–600 mg PO | 75 mg daily | COR 1 |
| Cangrelor (IV, cath-lab bridge) | 30 µg/kg bolus | 4 µg/kg/min infusion | COR 2a |
Parenteral anticoagulation
| Agent | Dose | Notes | Strength |
|---|---|---|---|
| UFH | 60 U/kg bolus (max 4,000 U), 12 U/kg/h (max 1,000 U/h) | Standard for PCI; target ACT 250–350 s (200–250 with GP IIb/IIIa) | COR 1 |
| Bivalirudin | 0.75 mg/kg bolus, 1.75 mg/kg/h infusion | Alternative at PCI; less bleeding than UFH + GP IIb/IIIa | COR 1 |
| Enoxaparin | 1 mg/kg SC q12h (0.75 mg/kg q12h if ≥75 y; 1 mg/kg q24h if CrCl <30) | Preferred for initial medical management of NSTE-ACS | COR 1 |
| Fondaparinux | 2.5 mg SC daily | Lowest bleeding risk; add UFH bolus at PCI (catheter thrombosis risk) | COR 2a |
Lipid-lowering therapy
| Agent | Recommendation | Strength |
|---|---|---|
| High-intensity statin | Start in-hospital regardless of baseline LDL-C (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) | COR 1 |
| Ezetimibe | Add if LDL-C ≥70 mg/dL on maximally tolerated statin | COR 1 |
| PCSK9 inhibitor | Add if LDL-C still ≥70 on statin + ezetimibe | COR 1 |
| Inclisiran / bempedoic acid | Alternatives for statin-intolerant or refractory LDL-C | COR 2a / 2b |
Reassess LDL-C at 4–8 weeks post-ACS. COR 1
Other medical therapy
- Beta-blocker: start within 24 h if no heart failure, low-output state, or risk of cardiogenic shock. COR 1
- ACEi/ARB: start within 24 h for anterior STEMI, heart failure, LVEF ≤40%, diabetes, or stable CKD. COR 1
- Aldosterone antagonist: add if LVEF ≤40% + HF or DM, already on ACEi + beta-blocker, CrCl >30, K <5. COR 1
- Oxygen: only if SpO2 <90%. Routine supplemental O2 is COR 3 (no benefit).
- PPI: co-prescribe with DAPT when GI bleed risk is elevated. COR 1
Reperfusion strategy (STEMI)
- Primary PCI is the preferred strategy. Target: first medical contact (FMC)-to-device ≤90 min at a PCI-capable center, ≤120 min if transfer required. COR 1
- Fibrinolytic therapy if anticipated FMC-to-device >120 min. Tenecteplase preferred (weight-based single IV bolus). Give within 30 min of arrival. COR 1
- Post-lytic angiography within 2–24 h (routine, not rescue-only). COR 1
- Urgent CABG: when PCI not feasible for the culprit anatomy or failed PCI with ongoing ischemia. COR 1
Invasive strategy (NSTE-ACS)
| Risk | Timing | Triggers | Strength |
|---|---|---|---|
| Very high | Immediate (<2 h) | Refractory angina, hemodynamic instability, cardiogenic shock, mechanical complication, sustained VT/VF | COR 1 |
| High | Early (≤24 h) | GRACE >140, troponin rise, new ST changes | COR 1 |
| Intermediate | Routine (≤72 h) | Diabetes, CKD (eGFR <60), LVEF <40%, prior PCI/CABG, GRACE 109–140 | COR 1 |
| Low | Selective / ischemia-guided | HEART ≤3, no troponin rise, low GRACE | COR 2a |
Key decisions
Cath-lab choices
- Radial access over femoral. Radial reduced death by 24% and major bleeding by 51% in ACS trials. COR 1
- Intracoronary imaging (IVUS or OCT) for left main, complex, or ambiguous lesions. COR 1
- Multivessel PCI of non-culprit lesions during the index hospitalization in hemodynamically stable STEMI (COMPLETE trial). COR 1
- Aspiration thrombectomy: routine use offers no benefit. COR 3 (no benefit)
Cardiogenic shock
Mechanical circulatory support in ACS-related cardiogenic shock
- Culprit-vessel PCI or CABG for the infarct-related artery. COR 1
- Multivessel PCI in shock is HARMFUL — culprit-only strategy preferred (CULPRIT-SHOCK: multivessel PCI ↑ 30-day death + RRT). COR 3 (harm)
- Microaxial flow pump (Impella) — upgraded to COR 2a based on DanGer Shock (n=360): 12.7% absolute mortality reduction at 180 d (NNT = 8). Trade-offs: more bleeding, limb ischemia, and need for renal replacement.
- IABP: no mortality benefit (IABP-SHOCK II). COR 3 (no benefit)
- VA-ECMO: no mortality benefit (ECLS-SHOCK). COR 3 (no benefit)
Post-MI complications
- ICD: wait ≥40 days post-MI; implant if LVEF ≤40% despite guideline-directed medical therapy. COR 1
- Post-MI pericarditis: acetaminophen first-line. For persistent symptoms, high-dose aspirin + colchicine. Avoid NSAIDs and glucocorticoids (impair healing). COR 1
- LV thrombus: anticoagulate ≥3 months. DOAC reasonable as alternative to warfarin. COR 2a
- Transfusion threshold: Hgb ≥10 g/dL is reasonable (MINT trial). COR 2b
Duration & stopping: DAPT strategies
| Strategy | Duration | Who | Strength |
|---|---|---|---|
| Standard DAPT | 12 months (aspirin + P2Y12) | Default for all ACS after PCI | COR 1 |
| P2Y12 monotherapy (ticagrelor) | Drop aspirin after ≥1 month DAPT, continue P2Y12 alone | Reduces bleeding without increasing ischemic events (TWILIGHT, TICO) | COR 1 |
| De-escalation to clopidogrel | Switch from ticagrelor/prasugrel to clopidogrel after 1 month | High bleeding risk; guided by platelet function or genotype testing | COR 2b |
| Short DAPT + SAPT | 1–3 months DAPT, then single antiplatelet | High bleeding risk (MASTER DAPT) | COR 2b |
| ACS + OAC (triple → dual) | Triple therapy 1–4 weeks, then OAC + P2Y12 (drop aspirin) | AF or other indication for anticoagulation (AUGUSTUS) | COR 1 |
Secondary prevention at discharge
- Cardiac rehabilitation: refer all ACS patients. COR 1
- Influenza vaccination: annually for all. COR 1
- Colchicine 0.5 mg daily: may reduce recurrent CV events (COLCOT, LoDoCo2). COR 2b
- SGLT2 inhibitors post-ACS: did not reduce the primary composite of CV death + HF hospitalization (DAPA-MI, EMPACT-MI); no specific ACS indication yet.
What’s changed since the 2025 guideline
Reviewer synthesis of evidence published after the guideline’s literature search cutoff (~April 2024). Not guideline text.
- Colchicine: CLEAR SYNERGY weakens the case in acute STEMI. This large RCT (n = 7,062) randomized acute STEMI patients to colchicine vs placebo and found NO reduction in MACE over 3 years. The guideline’s COR 2b rests on COLCOT (started median 14 d post-MI) and LoDoCo2 (stable CAD); CLEAR SYNERGY suggests the benefit, if any, may be limited to later/chronic-phase use, not the acute setting. NEJM 2024; PMID 39555823
- GLP-1 RA: SOUL strengthens the case for semaglutide at discharge in diabetic ACS. Oral semaglutide reduced MACE by 14% (HR 0.86; 0.77–0.96) in 9,650 patients with T2DM and established ASCVD. The guideline lists GLP-1 RA post-ACS as an evidence gap. SOUL does not study the acute phase, but it adds to the post-discharge argument for eligible T2DM patients. NEJM March 2025; PMID 40162642
- DAPT duration: DUAL-ACS supports shorter DAPT. 5,052 ACS patients randomized to 3-month vs 12-month DAPT, then P2Y12 monotherapy. 3-month DAPT was potentially non-inferior for ischemia with a trend to less bleeding. Extends the ticagrelor monotherapy data already endorsed (COR 1). ESC 2025 Hot-Line
- Aspirin-free strategy from the start: NEO-MINDSET says not yet. ~3,400 ACS patients randomized to IMMEDIATE aspirin-free P2Y12 monotherapy vs standard DAPT after PCI. Failed to demonstrate non-inferiority. Supports the guideline’s ≥1 month DAPT minimum before aspirin withdrawal. ESC 2025 Hot-Line
- SGLT2i post-ACS: EMPACT-MI secondary analysis. Empagliflozin showed cardio-renal benefits in subgroup analysis, but the primary composite (CV death + HF hospitalization) remained neutral. No change to the guideline’s position. 2025 secondary analysis
- In-hospital lipid-lowering: ESC/EAS pushes harder. The 2025 ESC/EAS lipid guideline update advocates more aggressive in-hospital LDL-C reduction with combination statin + ezetimibe from admission rather than statin-first, step-up-later. Aligns with but intensifies the ACC/AHA approach. ESC/EAS 2025 lipid guideline update
Anki cards minted this run
- PPCI timing: FMC-to-device ≤90 min (walk-in) / ≤120 min (transfer); fibrinolytic if >120 min to PCI (tenecteplase preferred)
- DAPT → P2Y12 monotherapy: After ≥1 month DAPT, drop aspirin and continue ticagrelor alone (COR 1; TWILIGHT, TICO)
- DanGer Shock / Impella: Microaxial flow pump COR 2a in STEMI cardiogenic shock (12.7% absolute mortality reduction, NNT = 8; more bleeding, limb ischemia, RRT)
- Cardiogenic shock PCI: Culprit-only (COR 1) — multivessel PCI in shock is COR 3 harm (CULPRIT-SHOCK)
Sources
- 1. Jneid H, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. J Am Coll Cardiol. 2025. DOI: 10.1016/j.jacc.2024.11.009
- 2. Jolly SS, et al. Colchicine in Acute Myocardial Infarction (CLEAR SYNERGY / OASIS 9). N Engl J Med. 2024. PMID: 39555823
- 3. Husain M, et al. Oral Semaglutide and Cardiovascular Outcomes in Type 2 Diabetes (SOUL). N Engl J Med. 2025. PMID: 40162642
- 4. DUAL-ACS trial. 3-month vs 12-month DAPT in ACS. ESC 2025 Hot-Line presentation.
- 5. NEO-MINDSET trial. Immediate aspirin-free P2Y12 monotherapy after PCI in ACS. ESC 2025 Hot-Line presentation.
- 6. Mehran R, et al. Ticagrelor With or Without Aspirin After PCI (TWILIGHT). N Engl J Med. 2019;381:2032–42.
- 7. Mehta SR, et al. Complete Revascularization With Multivessel PCI for Myocardial Infarction (COMPLETE). N Engl J Med. 2019;381:1411–21.
- 8. Thiele H, et al. PCI Strategies in Cardiogenic Shock (CULPRIT-SHOCK). N Engl J Med. 2017;377:2419–32.
- 9. Møller JE, et al. Microaxial Flow Pump in Cardiogenic Shock (DanGer Shock). N Engl J Med. 2024;390:1382–93.
- 10. Lopes RD, et al. Antithrombotic Therapy After ACS in Patients With AF (AUGUSTUS). N Engl J Med. 2019;380:1509–24.