Skip to content

Acute coronary syndromes

TL;DR — Acute coronary syndromes (ACS) comprise STEMI, NSTEMI, and unstable angina, defined by symptoms, ECG, serial high-sensitivity troponin, and evidence of ischemia rather than by chest pain alone (Bhatt 2022, PMID 35166796). STEMI is a time-critical reperfusion emergency: primary PCI is preferred when it can be delivered promptly; fibrinolysis remains relevant when timely PCI is not feasible and contraindications are absent (Dalby 2003, PMID 14530206; Byrne 2023, PMID 37622654). NSTEMI management is risk-stratified, combining antithrombotic therapy and invasive evaluation while explicitly accounting for bleeding, kidney disease, age, and competing diagnoses (Collet 2021, PMID 32860058; Rao 2025, PMID 40014670). Complete revascularization after STEMI with multivessel disease reduces recurrent ischemic events compared with culprit-only PCI, with timing individualized after the culprit artery is secured (Mehta 2019, PMID 31475795; Stähli 2023, PMID 37634190). Post-ACS care begins before discharge: intensive lipid lowering, appropriate antithrombotics, rehabilitation, smoking cessation, and management of LV dysfunction determine long-term risk.

Classification

Syndrome ECG Troponin Typical mechanism
STEMI Persistent ST elevation or equivalent occlusion pattern Usually rises, but reperfusion cannot await a late result Acute coronary occlusion, usually thrombosis
NSTEMI No persistent ST elevation; may show depression/T-wave change or be normal Rise/fall with myocardial injury plus ischemic evidence Subtotal occlusion, distal embolization, supply–demand mismatch, or other
Unstable angina No persistent ST elevation No acute injury above assay threshold Ischemia without detectable necrosis; less common with hs-troponin
Type 2 MI Variable Rise/fall plus ischemia Oxygen supply–demand imbalance without acute atherothrombosis
Non-ischemic myocardial injury Variable Rise/fall or chronic elevation Myocarditis, heart failure, renal disease, sepsis, tachyarrhythmia, other

High-sensitivity troponin detects injury, not mechanism. A value above the reference limit does not by itself establish type 1 MI, and normal early values require timing-aware serial algorithms (Bhatt 2022, PMID 35166796; White 2021, PMID 33372537).

Immediate diagnostic priorities

  1. Obtain and interpret a 12-lead ECG rapidly; repeat it when symptoms persist or evolve.
  2. Identify shock, pulmonary edema, malignant arrhythmia, mechanical complication, or ongoing refractory ischemia.
  3. Measure serial high-sensitivity troponin without delaying reperfusion for a diagnostic STEMI pattern.
  4. Give antithrombotic and anti-ischemic treatment matched to the working diagnosis and bleeding risk.
  5. Activate a reperfusion or invasive pathway and document symptom-onset, first-medical-contact, and treatment times (Byrne 2023, PMID 37622654; Rao 2025, PMID 40014670).

Posterior, right-ventricular, and left-main/multivessel ischemia can be under-recognized on a standard ECG. Persistent symptoms with a nondiagnostic tracing require repeat or additional leads and integration with imaging and biomarkers (Vogel 2019, PMID 31171787).

STEMI reperfusion

Strategy Preferred context Central trade-off
Primary PCI Promptly available experienced system Best artery opening and lower reinfarction/stroke than lysis, but benefit erodes with delay
Fibrinolysis Early presentation when timely PCI cannot be delivered Faster drug delivery but bleeding/ICH risk and failed reperfusion
Pharmaco-invasive Lysis followed by transfer/angiography Preserves early treatment while enabling rescue/routine PCI
Rescue PCI Failed fibrinolysis or recurrent instability Procedural risk versus persistent occlusion

A meta-analysis of transfer for primary angioplasty versus immediate thrombolysis supported transfer when delays were controlled, illustrating that the relevant comparison is a system strategy, not simply a device versus a drug (Dalby 2003, PMID 14530206).

Contraindications to fibrinolysis—especially prior intracranial hemorrhage, active bleeding, suspected aortic dissection, or major recent intracranial pathology—must be checked explicitly. When cardiogenic shock or mechanical complications are suspected, reperfusion occurs alongside hemodynamic and surgical evaluation (Byrne 2023, PMID 37622654).

NSTEMI and unstable angina

NSTEMI risk is heterogeneous. Immediate angiography is reserved for instability such as shock, recurrent/refractory ischemia, life-threatening arrhythmia, or acute heart failure; early invasive evaluation is favored for high-risk patients, while lower-risk pathways can be selective (Collet 2021, PMID 32860058; Rao 2025, PMID 40014670).

Risk dimension Findings increasing urgency or complexity
Ischemic Dynamic ST change, recurrent pain, large troponin rise, prior revascularization, diabetes
Hemodynamic Hypotension, shock, pulmonary edema
Electrical Ventricular arrhythmia, resuscitated arrest
Bleeding Prior hemorrhage, anemia, frailty, anticoagulation, low body weight
Renal CKD increases ischemic, contrast, and bleeding risks simultaneously
Diagnostic Sepsis, pulmonary embolism, myocarditis, Takotsubo, dissection, MINOCA

A meta-analysis of older biomarker-reporting trials found that a routine invasive strategy lowered death or recurrent non-fatal MI across combined unstable angina/NSTEMI populations (RR 0.79, 95% CI 0.70–0.90) but not within NSTEMI alone (RR 1.19, 95% CI 1.03–1.38), and carried an early hazard from randomization to discharge (RR 1.29 in UA/NSTEMI; 1.82 in NSTEMI) — so the benefit rests heavily on trials enrolling many unstable-angina patients, and older trials, changing troponin assays, and crossovers complicate transport to current practice (Manfrini 2016, PMID 27273697; George 2019, PMID 30969393). In CKD, observational and randomized evidence is thinner and the risk–benefit balance changes with stage (Fong 2023, PMID 37639763).

Antithrombotic treatment in ACS

Phase Typical components Decision pressure
Initial Aspirin plus parenteral anticoagulation; add P2Y12 inhibitor according to strategy Diagnosis, PCI timing, CABG possibility, bleeding risk
PCI Anticoagulation plus antiplatelet therapy; radial access favored Stent thrombosis versus access/non-access bleeding
Discharge DAPT for a default period, shortened or modified when bleeding risk dominates ACS recurrence, stent features, anticoagulation need
Long term Usually single antiplatelet; selected intensified strategies Residual ischemic risk versus cumulative bleeding

Bleeding is not a benign counterweight: major bleeding predicts mortality and can force cessation of antithrombotic therapy. Ischemic and bleeding risks share predictors, so a single “high-risk” label is insufficient (Chew 2020, PMID 32646566).

Multivessel disease and complete revascularization

After successful culprit-lesion PCI in STEMI, COMPLETE showed that staged PCI of suitable non-culprit lesions reduced cardiovascular death or MI and reduced cardiovascular death, MI, or ischemia-driven revascularization compared with culprit-only treatment (Mehta 2019, PMID 31475795).

DANAMI-3–PRIMULTI supported FFR-guided complete revascularization, principally through fewer repeat revascularizations (Engstrøm 2015, PMID 26347918). MULTISTARS AMI randomized 840 hemodynamically stable patients to immediate versus staged (19–45 days) multivessel PCI: the 1-year composite of death, nonfatal MI, stroke, unplanned ischemia-driven revascularization, or heart-failure hospitalization occurred in 8.5% versus 16.3% (risk ratio 0.52, 95% CI 0.38–0.72; noninferior and superior), driven by nonfatal MI and unplanned revascularization rather than death (Stähli 2023, PMID 37634190). The trial excluded shock, so timing still depends on stability, contrast load, lesion complexity, and local expertise.

Complete revascularization evidence does not authorize indiscriminate treatment during shock; shock physiology and culprit certainty require a separate evidence frame.

Post-ACS disease modification

Intervention Evidence anchor Quantitative signal
Intensive LDL lowering Add ezetimibe after ACS in IMPROVE-IT Modest but significant incremental event reduction (Cannon 2015, PMID 26039521)
Anti-inflammatory therapy COLCOT Colchicine 0.5 mg: primary composite HR 0.77 (Tardif 2019, PMID 31733140)
Complete revascularization COMPLETE Fewer CV death/MI and ischemia-driven events (Mehta 2019, PMID 31475795)
Cardiac rehabilitation RCT meta-analysis CV mortality RR 0.74; NNT about 37 (Dibben 2023, PMID 36746187)
Beta-blocker with preserved EF REDUCE-AMI No reduction in death/new MI with routine long-term use (Yndigegn 2024, PMID 38587241)

Contemporary beta-blocker evidence is more conditional than historical practice. REDUCE-AMI found no benefit in patients revascularized after acute MI with preserved EF; ABYSS did not establish that interruption was noninferior to continuation in stable post-MI patients, leaving individualized uncertainty rather than a universal stop rule (Yndigegn 2024, PMID 38587241; Silvain 2024, PMID 39213187).

Before discharge, LV function, renal function, lipids, glycemic status, smoking, psychosocial status, adherence barriers, and rehabilitation referral should be documented. Secondary prevention failure is often a transition-of-care failure, not drug failure.

Discharge documentation should also state the MI mechanism, treated and untreated anatomy, antithrombotic stop/review dates, pending titrations, and the responsible follow-up team; these fields make later bleeding and revascularization decisions auditable (Rao 2025, PMID 40014670).

Sex differences and diagnostic safety

Women with ACS report chest pain commonly, but pooled evidence shows differences in accompanying symptoms and presentation frequency; “atypical” should not be used as a synonym for “female” or “non-cardiac” (van Oosterhout 2020, PMID 32363989).

Use of sex-specific troponin thresholds changes MI recognition and can identify women whose injury would be missed by a single uniform cutoff, although diagnosis still requires clinical ischemia (Ferry 2019, PMID 31431112).

Unsafe shortcut Safer inference
“No crushing pain, therefore no ACS” Integrate symptom constellation, ECG, serial troponin, and risk
“Troponin positive, therefore plaque rupture” Determine ischemic mechanism and competing injury causes
“Young, therefore low risk” Consider smoking, familial lipids, pregnancy-related and inflammatory risks
“Normal first ECG/troponin, therefore discharged” Apply validated serial pathway and timing
“Bleeding risk means no antithrombotics” Choose agent, dose, access, duration, and protection proportionately

Boundary conditions from comparative trials

Decision Quantified evidence What it does not justify
Primary PCI versus fibrinolysis In the 1,572-patient DANAMI-2 age analysis, the composite benefit of PCI was consistent across age strata (overall treatment P=0.006; interaction P=0.50), although mortality alone was not reduced (Fosbøl 2008, PMID 18657676). Age alone is not a reason to withhold PCI, but this does not erase delay, frailty, bleeding, or goals-of-care considerations.
Pharmaco-invasive rescue when PCI is delayed STREAM-2 randomized 604 patients aged ≥60 years: death/shock/HF/reinfarction was 12.8% with half-dose tenecteplase versus 13.3% with PCI (RR 0.96, 95% CI 0.62–1.48), but intracranial hemorrhage occurred in 1.5% versus 0% (Van de Werf 2023, PMID 37439219). Similar imprecise efficacy estimates do not make fibrinolysis interchangeable with timely PCI; contraindication and anticoagulant-dose discipline remain decisive.
Complete PCI after uncomplicated multivessel MI COMPLETE reduced cardiovascular death or MI with staged or in-hospital nonculprit PCI in hemodynamically stable patients (Mehta 2019, PMID 31475795), consistent with DANAMI-3–PRIMULTI's physiology-guided direction (Engstrøm 2015, PMID 26347918). The result cannot be transferred to cardiogenic shock.
Culprit-only PCI in cardiogenic shock CULPRIT-SHOCK found death or renal-replacement therapy at 30 days in 45.9% with culprit-only versus 55.4% with immediate multivessel PCI (RR 0.83, 95% CI 0.71–0.96) (Thiele 2017, PMID 29083953). “Complete revascularization” is not a universal same-sitting rule.
Immediate versus delayed NSTEMI angiography In RIDDLE-NSTEMI (n=323), death/new MI at 30 days was 4.3% versus 13.0% (HR 0.32, 95% CI 0.13–0.74), driven mainly by pre-catheterization MI (Milosevic 2016, PMID 26777321). One modest trial does not establish immediate angiography for every NSTE-ACS phenotype.

The 2023 ESC and 2025 US ACS guidelines converge on rapid reperfusion, risk-based invasive care, radial access, antiplatelet therapy, and secondary prevention, but convert heterogeneous timing evidence into somewhat different operational language (Byrne 2023, PMID 37622654; Rao 2025, PMID 40014670). Reviews of unstable-angina and CKD evidence show why certainty falls when biomarker-negative disease, advanced CKD, frailty, or shock replaces the typical trial population (Manfrini 2016, PMID 27273697; Fong 2023, PMID 37639763). The defensible synthesis is phenotype-specific: occlusion and shock physiology override generic “early versus late” labels, and spontaneous MI, procedural MI, bleeding, stroke, AKI, and mortality should be reported separately (Vogel 2019, PMID 31171787; Bhatt 2022, PMID 35166796).

Interventions that should not be treated as automatic

Routine adjuncts require their own randomized evidence. In MATRIX, radial rather than femoral access reduced net adverse clinical events in NSTE-ACS (12.2% vs 14.7%; RR 0.82, 95% CI 0.69–0.97), while the STEMI estimate was directionally similar but imprecise (7.2% vs 8.3%; RR 0.86, 95% CI 0.68–1.08); mortality and actionable access-site bleeding favored radial access without evidence of interaction by ACS type (Vranckx 2017, PMID 28329389). By contrast, DETO2X-AMI found no mortality benefit from routine oxygen when baseline saturation was ≥90% (5.0% vs 5.1%; HR 0.97, 95% CI 0.79–1.21), despite reducing subsequent hypoxemia (Hofmann 2017, PMID 28844200).

Escalation in cardiogenic shock is also not synonymous with benefit. ECLS-SHOCK found 30-day mortality of 47.8% with early extracorporeal life support versus 49.0% with usual care (RR 0.98, 95% CI 0.80–1.19), while moderate/severe bleeding rose from 9.6% to 23.4% and vascular complications requiring intervention from 3.8% to 11.0% (Thiele 2023, PMID 37634145). At the other end of the age-risk spectrum, the 167-patient MOSCA-FRAIL subanalysis found no reduction in reinfarction with routine invasive care over median 3 years (subdistribution HR 0.87, 95% CI 0.54–1.40); death occurred in 56%, making competing mortality central rather than a statistical nuisance (Sanchis 2025, PMID 39922692).

Open questions

  • Which NSTEMI patients with advanced CKD gain net benefit from an early invasive strategy? (Fong 2023, PMID 37639763)
  • What is the optimal timing and physiologic/imaging selection for non-culprit PCI after STEMI? (Mehta 2019, PMID 31475795; Stähli 2023, PMID 37634190)
  • Which post-MI patients with preserved EF still benefit from beta-blockers—those with arrhythmia, residual ischemia, hypertension, or another phenotype? (Yndigegn 2024, PMID 38587241; Silvain 2024, PMID 39213187)
  • Can bleeding-risk-guided antithrombotic de-escalation preserve ischemic protection across underrepresented groups? (Chew 2020, PMID 32646566)
  • How should type 2 MI trials define mechanism-specific therapy rather than aggregating heterogeneous injury? (White 2021, PMID 33372537)

References

  1. Bhatt DL, et al. Diagnosis and Treatment of Acute Coronary Syndromes: A Review. JAMA. 2022;327:662-675. PMID 35166796
  2. Dalby M, et al. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis. Circulation. 2003;108:1809-14. PMID 14530206
  3. Byrne RA, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44:3720-3826. PMID 37622654
  4. Collet JP, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42:1289-1367. PMID 32860058
  5. Rao SV, 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:e771-e862. PMID 40014670
  6. Mehta SR, et al. Complete Revascularization with Multivessel PCI for Myocardial Infarction. N Engl J Med. 2019;381:1411-1421. PMID 31475795
  7. Stähli BE, et al. Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction. N Engl J Med. 2023;389:1368-1379. PMID 37634190
  8. White HD, et al. Adding Insult to Injury: Are There Treatments for Myocardial Injury and Type 2 Myocardial Infarction? J Am Heart Assoc. 2021;10:e019796. PMID 33372537
  9. Vogel B, et al. ST-segment elevation myocardial infarction. Nat Rev Dis Primers. 2019;5:39. PMID 31171787
  10. Manfrini O, et al. Early Invasive Strategy for Unstable Angina: a New Meta-Analysis of Old Clinical Trials. Sci Rep. 2016;6:27345. PMID 27273697
  11. George B, et al. Revascularization Strategies for Non-ST-Elevation Myocardial Infarction. Curr Cardiol Rep. 2019;21:39. PMID 30969393
  12. Fong KY, et al. Role of Invasive Strategy for Non-ST-Elevation Myocardial Infarction in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis. Am J Cardiol. 2023;205:369-378. PMID 37639763
  13. Chew DP, et al. Mortality From Bleeding Versus Myocardial Infarction: Loosening A Strand of the Antithrombotic Therapy "Gordian Knot". J Am Coll Cardiol. 2020;76:172-174. PMID 32646566
  14. Engstrøm T, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial. Lancet. 2015;386:665-71. PMID 26347918
  15. Cannon CP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372:2387-97. PMID 26039521
  16. Tardif JC, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381:2497-2505. PMID 31733140
  17. Dibben GO, et al. Exercise-based cardiac rehabilitation for coronary heart disease: a meta-analysis. Eur Heart J. 2023;44:452-469. PMID 36746187
  18. Yndigegn T, et al. Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. N Engl J Med. 2024;390:1372-1381. PMID 38587241
  19. Silvain J, et al. Beta-Blocker Interruption or Continuation after Myocardial Infarction. N Engl J Med. 2024;391:1277-1286. PMID 39213187
  20. van Oosterhout REM, et al. Sex Differences in Symptom Presentation in Acute Coronary Syndromes: A Systematic Review and Meta-analysis. J Am Heart Assoc. 2020;9:e014733. PMID 32363989
  21. Ferry AV, et al. Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex-Specific Criteria. J Am Heart Assoc. 2019;8:e012307. PMID 31431112
  22. Fosbøl EL, et al. Long-term outcome of primary angioplasty compared with fibrinolysis across age groups: a Danish Multicenter Randomized Study on Fibrinolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2) substudy. Am Heart J. 2008;156:391-6. PMID 18657676
  23. Van de Werf F, et al. STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial. Circulation. 2023;148:753-764. PMID 37439219
  24. Thiele H, et al. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N Engl J Med. 2017;377:2419-2432. PMID 29083953
  25. Milosevic A, et al. Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients: The RIDDLE-NSTEMI Study. JACC Cardiovasc Interv. 2016;9:541-9. PMID 26777321
  26. Vranckx P, et al. Radial versus femoral access in patients with acute coronary syndromes with or without ST-segment elevation. Eur Heart J. 2017;38:1069-1080. PMID 28329389
  27. Hofmann R, et al. Oxygen Therapy in Suspected Acute Myocardial Infarction. N Engl J Med. 2017;377:1240-1249. PMID 28844200
  28. Thiele H, et al. Extracorporeal Life Support in Infarct-Related Cardiogenic Shock. N Engl J Med. 2023;389:1286-1297. PMID 37634145
  29. Sanchis J, et al. Effects of routine invasive management on reinfarction risk in older adults with frailty and non-ST-segment elevation myocardial infarction: a subanalysis of a randomised clinical trial. Heart. 2025;111:786-792. PMID 39922692