Acute Coronary Syndrome (ACS)

Definition and Classification

• Goldman-Cecil Medicine, p. 638

Epidemiology

• ~1.2 million Americans hospitalized annually with ACS
• About two-thirds have NSTE-ACS; one-third have STEMI

• 50% of NSTE-ACS patients are older than 65 years; nearly half are women

• Strong associations with atherosclerosis risk factors, peripheral vascular disease, and chronic inflammatory disorders (rheumatoid arthritis, psoriasis, lupus)

Pathophysiology

Type 1 MI - Plaque Rupture (Most Common)

• Oxidized LDL deposition triggers macrophage and T-lymphocyte infiltration at the plaque border
• These inflammatory cells secrete cytokines (TNF, IL-1, IFN-γ) that inhibit collagen synthesis and enzymes (matrix metalloproteinases, cathepsins) that degrade collagen and elastin, thinning the fibrous cap
• Sites of low shear stress (vessel bifurcations) accumulate lipids and inflammatory cells, accelerating cap thinning
• Plaque neovascularization (driven by VEGF, FGF, etc.) makes the plaque structurally fragile

Type 2 MI - Supply/Demand Mismatch

• Reduced supply: hypotension, severe anemia, hypoxemia, coronary vasospasm (Prinzmetal angina), cocaine, triptans, spontaneous coronary artery dissection (SCAD - especially peripartum women)
• Increased demand: tachycardia, severe hypertension, thyrotoxicosis

• Goldman-Cecil Medicine, p. 638-639

Clinical Presentation

• Substernal chest pain/pressure, often radiating to the left arm, jaw, or back
• Diaphoresis, nausea, dyspnea

• Dyspnea alone, syncope, fatigue, weakness, abdominal pain, delirium
• "Classic" chest pain occurs in only ~50% of patients aged ≥85 years
• One-third of women >65 years with AMI present with abdominal pain alone
• Acute heart failure at presentation occurs in ~50% of STEMI patients ≥85 years (vs. 1.7% in those <65)

• Rosen's Emergency Medicine, p. 4015-4021

Diagnosis

ECG

• STEMI: New ST elevation ≥1 mm in ≥2 contiguous limb leads, or ≥2 mm in ≥2 contiguous precordial leads (or new LBBB)
• NSTEMI/UA: ST depression, T-wave inversions, or normal ECG
• Serial ECGs should be obtained if initial is non-diagnostic

Biomarkers

• High-sensitivity troponin (hsTn) is the cornerstone biomarker - can detect myonecrosis within 1-3 hours of symptom onset
• Serial measurements at 0h and 1-3h (or 0h/3h/6h depending on assay)
• Unstable angina: troponin remains negative throughout

Risk Stratification Scores

• Age ≥65, ≥3 CAD risk factors, prior coronary stenosis ≥50%, ST deviation on ECG, ≥2 anginal events in prior 24h, aspirin use in prior 7 days, elevated cardiac markers
• Score 0-2 = low risk; 3-4 = intermediate; 5-7 = high risk
• Advantage: simple integer sum, calculable at bedside without a computer

• Derived from a large international registry (less-selected population)
• Score ≥140 = high risk; better calibration between predicted and observed mortality than TIMI
• Includes renal insufficiency as a variable (an advantage over TIMI)
• Available at gracescore.org
• Fuster and Hurst's The Heart, 15th Ed.; Sabiston Textbook of Surgery

Management

Immediate General Measures (MONA-B framework)

• Monitoring: continuous ECG, pulse oximetry, IV access
• Oxygen: only if SpO2 <90%
• Nitrates: sublingual/IV for ongoing ischemia (contraindicated if hypotension, RV infarction, or PDE5 inhibitor use within 24-48h)
• Aspirin: 325 mg chewed loading dose immediately for all ACS
• Beta-blockers: oral, within 24h if no signs of HF, low-output state, or AV block (reduce heart rate and myocardial oxygen demand)

Antithrombotic Therapy

• Aspirin 75-100 mg/day indefinitely
• P2Y12 inhibitor added to aspirin for 12 months:
  • Ticagrelor (preferred over clopidogrel - faster onset, more potent, shown to reduce mortality in PLATO trial)
  • Prasugrel (use for PCI patients; avoid if history of TIA/stroke, age >75, weight <60kg)
  • Clopidogrel (alternative, especially if ticagrelor/prasugrel contraindicated or not available)

• Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH, e.g., enoxaparin), fondaparinux, or bivalirudin
• LMWH/fondaparinux preferred over UFH for NSTE-ACS in most patients (lower bleeding risk)
• Anticoagulation continued through PCI or until hospital discharge in medically managed patients

Invasive Strategy Timing (NSTE-ACS)

STEMI-Specific Management

• Primary PCI is the gold standard - target door-to-balloon time <90 minutes (or <120 minutes if transferred)
• Fibrinolysis (alteplase, tenecteplase) if PCI not available within 120 minutes of first medical contact; followed by "pharmaco-invasive" strategy (coronary angiography within 24h)

Other Medications

• High-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg): started in-hospital, continued indefinitely - stabilize plaque, reduce LDL
• ACE inhibitors/ARBs: for all patients with EF <40%, hypertension, or diabetes
• Aldosterone antagonists (eplerenone): if EF <40% post-MI, no significant renal impairment or hyperkalemia

Complications

Secondary Prevention (Post-ACS)

• Aspirin indefinitely
• P2Y12 inhibitor for 12 months (duration may be adjusted based on bleeding vs. ischemic risk)
• High-intensity statin indefinitely
• Beta-blocker (especially if reduced EF)
• ACE inhibitor/ARB
• Cardiac rehabilitation
• Risk factor modification: smoking cessation, BP control, diabetes management, weight loss

Recent Evidence Updates (2024-2026)

1. DAPT de-escalation (Valgimigli et al., Lancet 2024, PMID 39226909): De-escalation to ticagrelor monotherapy (dropping aspirin after 1-3 months) vs. 12 months of DAPT - individual patient-level meta-analysis showing reduced bleeding without excess ischemic risk.
2. Elderly ACS - invasive vs. conservative (Reddy et al., JAMA Intern Med 2025, PMID 40549394): Meta-analysis of early invasive vs. conservative strategy in older patients with ACS - supports early invasive approach in selected elderly patients.
3. Aspirin vs. P2Y12 monotherapy post-PCI (Laudani et al., JACC Cardiovasc Interv 2025, PMID 40803759): Network meta-analysis comparing aspirin monotherapy vs. P2Y12 inhibitor monotherapy after PCI for ACS - ongoing evolution of post-PCI antithrombotic strategy.