1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI

1. Antithrombotic Therapy: DAPT & Anticoagulation

Dual Antiplatelet Therapy (DAPT)

1. Aspirin: 162-325 mg non-enteric chewable loading dose immediately, followed by 81 mg daily indefinitely.
2. P2Y12 Receptor Inhibitor Selection:
   • Ticagrelor (Brilinta): 180 mg loading dose, then 90 mg PO BID. Reversible, direct-acting P2Y12 inhibitor. Superior to Clopidogrel (PLATO trial). Side effects: dyspnea (self-limiting, related to adenosine reuptake inhibition), ventricular pauses, hyperuricemia.
   • Prasugrel (Effient): 60 mg loading dose, then 10 mg PO daily (5 mg daily if weight <60 kg). Potent irreversible thienopyridine. Superior to Clopidogrel (TRITON-TIMI 38). Strictly contraindicated in patients with a history of stroke or TIA (excess fatal ICH); not recommended in patients aged >=75 years unless high risk (DM or prior MI).
   • Clopidogrel (Plavix): 300-600 mg loading dose, then 75 mg PO daily. Indicated when Ticagrelor/Prasugrel are contraindicated, in patients with high bleeding risk, or when triple antithrombotic therapy is required.
3. DAPT Duration:
   • Standard ACS: 12 months minimum regardless of bare-metal stent (BMS), drug-eluting stent (DES), or medical therapy alone.
   • High Bleeding Risk (ARC-HBR): De-escalation or shortening to 1-6 months of DAPT followed by P2Y12 monotherapy (e.g., Ticagrelor or Clopidogrel) or Aspirin monotherapy.
   • Prolonged DAPT (>12 months): For patients with high ischemic risk (prior stent thrombosis, bifurcation stents, multivessel disease, DM) and low bleeding risk (DAPT score >=2), continuation of DAPT (e.g., Aspirin + Ticagrelor 60 mg BID via PEGASUS-TIMI 54) reduces recurrent ischemic events.

Anticoagulation Regimens

• Unfractionated Heparin (UFH): IV bolus 60 units/kg (max 4,000 units), then 12 units/kg/h (max 1,000 units/h) titrated to target aPTT 50-70 seconds. Anticoagulant of choice for primary PCI (target ACT 250-300 seconds without GP IIb/IIIa inhibitor).
• Low-Molecular-Weight Heparin (Enoxaparin): 1 mg/kg SC q12h (1 mg/kg SC q24h if CrCl <30 mL/min). Preferred over UFH in medically managed NSTE-ACS (SYNERGY trial).
• Bivalirudin: Direct thrombin inhibitor; alternative in PCI, particularly for patients with heparin-induced thrombocytopenia (HIT) or high bleeding risk.
• Fondaparinux: 2.5 mg SC daily (factor Xa inhibitor); lowest bleeding risk in NSTE-ACS. Must be supplemented with UFH bolus during PCI to prevent catheter-associated guide thrombosis.

2. Post-MI Guideline-Directed Secondary Prevention

Long-term medical therapy after MI significantly reduces mortality, recurrent reinfarction, and progressive ventricular remodeling:

1. High-Intensity Statin Therapy: Atorvastatin 80 mg daily or Rosuvastatin 40 mg daily started immediately regardless of baseline LDL-C. Goal is >=50% reduction in LDL-C and LDL-C <55 mg/dL (<1.4 mmol/L). If LDL-C remains >=70 mg/dL (or >=55 mg/dL per ACC/ESC) on maximally tolerated statin, add Ezetimibe 10 mg daily; add PCSK9 inhibitor if still above goal.
2. Beta-Blockers (Carvedilol, Metoprolol Succinate, Bisoprolol): Initiate within 24 hours in hemodynamically stable patients (no signs of acute HF, low-output state, bradycardia, or PR >240 ms). Continue for at least 3 years in patients with preserved EF, and indefinitely if LVEF <=40%.
3. ACE Inhibitor or ARB: Initiate within 24 hours in all patients with anterior infarction, LVEF <=40%, clinical heart failure, hypertension, or diabetes mellitus. Continue indefinitely.
4. Mineralocorticoid Receptor Antagonist (MRA - Eplerenone 25-50 mg or Spironolactone 25-50 mg): Class I indication for post-MI patients already on therapeutic doses of an ACEi/ARB and beta-blocker who have LVEF <=40% AND either clinical heart failure symptoms or diabetes mellitus (EPHESUS trial). Criteria: Serum K+ <=5.0 mEq/L and eGFR >=30 mL/min/1.73m2 (serum creatinine <=2.5 mg/dL in men, <=2.0 mg/dL in women).
5. Anti-anginal / Lifestyle: Sublingual nitroglycerin 0.4 mg PRN, cardiac rehabilitation referral, smoking cessation, annual influenza and pneumococcal vaccination.

3. Mechanical Complications of Myocardial Infarction

Mechanical complications typically develop 3 to 7 days post-MI (range: 1-14 days) due to coagulation necrosis, neutrophilic infiltration, and collagen lysis weakening the necrotic myocardial tissue. They are more frequent after transmural STEMI with delayed or absent reperfusion.

Board Exam Contrast — VSR vs. Papillary Muscle Rupture:

• Both present 3-7 days post-MI with severe hemodynamic deterioration and a new holosystolic murmur.
• Ventricular Septal Rupture: Murmur heard at LLSB, associated with a palpable thrill, and causes a step-up in oxygen saturation in the right ventricle on pulmonary artery catheterization.
• Papillary Muscle Rupture: Murmur heard at the apex radiating to the axilla, no thrill, normal RV O2 saturation, but demonstrates giant 'v' waves on the pulmonary capillary wedge pressure (PCWP) tracing.