What is the comprehensive pharmacologic management of acute myocardial infarction, including drug choices, indications, mechanisms of action, dosing, contraindications, and case application?

Comprehensive Pharmacotherapy Management of Acute Myocardial Infarction

Immediate Management (First Contact to Hospital Arrival)

Antiplatelet Therapy

Aspirin should be administered immediately at a dose of 162-325 mg, chewed (non-enteric coated formulation) for rapid buccal absorption, and this represents the single most critical initial pharmacologic intervention. 1

• Mechanism of Action: Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1), blocking thromboxane A2 production in platelets, achieving near-total platelet inhibition within minutes at doses ≥162 mg 1
• Dosing: Initial dose 162-325 mg chewed, then 75-100 mg daily indefinitely 1
• Contraindications: Known aspirin allergy (use clopidogrel 75 mg as alternative) 1
• Clinical Application: A 55-year-old presenting with chest pain and ST-elevations should chew 325 mg aspirin immediately upon EMS contact or emergency department arrival

Pain Management and Symptom Relief

Morphine sulfate 2-4 mg IV with increments of 2-8 mg repeated at 5-15 minute intervals is the analgesic of choice for ongoing ischemic chest pain. 1

• Mechanism: Opioid receptor agonist providing analgesia, anxiolysis, and venodilation (reducing preload)
• Indications: Persistent chest pain unrelieved by nitroglycerin
• Contraindications: Hypotension, respiratory depression, altered mental status

Sublingual nitroglycerin 0.4 mg should be given every 5 minutes for up to 3 doses for ongoing ischemic discomfort. 1

• Mechanism: Nitric oxide donor causing venodilation (reducing preload) and coronary vasodilation
• Indications: Ongoing chest pain, hypertension, pulmonary congestion 1
• Absolute Contraindications:
  • Systolic BP <90 mmHg or ≥30 mmHg below baseline 1
  • Heart rate <50 bpm or >100 bpm 1
  • Right ventricular infarction (suspect with inferior STEMI) 1
  • Phosphodiesterase inhibitor use within 24 hours (48 hours for tadalafil) 1
• Clinical Application: A patient with inferior STEMI and hypotension should NOT receive nitrates due to likely RV involvement

Beta-Blockers (Acute Phase)

Oral beta-blockers should be administered promptly to all patients without contraindications, regardless of reperfusion strategy. 1

• Mechanism: Beta-1 receptor blockade reduces myocardial oxygen demand by decreasing heart rate, contractility, and blood pressure
• Benefits: Reduces infarct size, reinfarction rates, and life-threatening ventricular arrhythmias 1
• Dosing: Metoprolol 25-50 mg orally every 6-12 hours initially
• IV Beta-Blockers: Reasonable for tachyarrhythmia or hypertension (Class IIa) 1, but MUST be avoided in patients with hypotension, acute heart failure, AV block, or severe bradycardia 1
• Clinical Application: A hemodynamically stable patient with anterior STEMI and heart rate 95 bpm should receive oral metoprolol; a patient with Killip class III heart failure should NOT receive IV beta-blockers

Reperfusion Strategy Pharmacotherapy

Primary PCI Pathway

Dual antiplatelet therapy with aspirin PLUS a potent P2Y12 inhibitor (prasugrel or ticagrelor preferred over clopidogrel) must be initiated before or at the time of PCI and continued for 12 months. 1

P2Y12 Inhibitors

• Ticagrelor (preferred):

  • Loading dose: 180 mg, maintenance: 90 mg twice daily
  • Mechanism: Reversible P2Y12 receptor antagonist preventing ADP-mediated platelet activation
  • Advantages: Faster onset, more potent than clopidogrel, reversible

• Prasugrel (preferred):

  • Loading dose: 60 mg, maintenance: 10 mg daily
  • Mechanism: Irreversible P2Y12 receptor antagonist (active metabolite)
  • Contraindications: Prior stroke/TIA, age ≥75 years (relative), weight <60 kg, increased bleeding risk

• Clopidogrel (if above unavailable/contraindicated):

  • Loading dose: 600 mg, maintenance: 75 mg daily 1
  • Mechanism: Irreversible P2Y12 receptor antagonist (prodrug requiring hepatic activation)

Anticoagulation for Primary PCI

Unfractionated heparin (UFH) with weight-adjusted bolus (70-100 units/kg) is standard anticoagulation during primary PCI. 1

• Alternatives: Bivalirudin (direct thrombin inhibitor), enoxaparin
• Fondaparinux is NOT recommended for primary PCI 1

Fibrinolytic Pathway

When primary PCI cannot be performed within 120 minutes of first medical contact, fibrinolytic therapy should be initiated within 12 hours of symptom onset, preferably pre-hospital. 1

Fibrinolytic Agents

Fibrin-specific agents (tenecteplase, alteplase, or reteplase) are recommended over non-fibrin-specific agents. 1

• Tenecteplase (preferred for ease of administration):

  • Single weight-based IV bolus
  • Mechanism: Tissue plasminogen activator converting plasminogen to plasmin, lysing fibrin clots

• Alteplase: 15 mg bolus, then 0.75 mg/kg over 30 min, then 0.5 mg/kg over 60 min

• Reteplase: Two 10-unit boluses 30 minutes apart

Adjunctive Therapy with Fibrinolysis

Clopidogrel 300 mg loading dose (75 mg if age >75) plus aspirin is mandatory with fibrinolytic therapy. 1

Anticoagulation with enoxaparin IV followed by subcutaneous (preferred over UFH) or UFH as weight-adjusted bolus plus infusion must be administered until revascularization or for hospital duration up to 8 days. 1

• Enoxaparin: 30 mg IV bolus, then 1 mg/kg SC every 12 hours (reduce dose if age >75 or CrCl <30)
• UFH: 60 units/kg bolus (max 4000 units), then 12 units/kg/hr infusion (max 1000 units/hr), titrate to aPTT 1.5-2× control

All patients receiving fibrinolysis must be transferred immediately to PCI-capable center for angiography at 2-24 hours post-successful lysis. 1

• Rescue PCI: Immediately if <50% ST-segment resolution at 60-90 minutes or hemodynamic/electrical instability 1

Long-Term Secondary Prevention (Post-Discharge)

Antiplatelet Therapy

Dual antiplatelet therapy (aspirin 75-100 mg daily PLUS ticagrelor or prasugrel or clopidogrel) must continue for 12 months post-MI unless excessive bleeding risk exists. 1

After 12 months, aspirin 75-100 mg daily should continue indefinitely. 1

Proton pump inhibitor (PPI) must be added in patients at high gastrointestinal bleeding risk receiving DAPT. 1

• High-risk features: Age >65, prior GI bleeding, anticoagulation use, NSAID use, H. pylori infection

Statin Therapy

High-intensity statin therapy must be initiated as early as possible (ideally in-hospital) and maintained indefinitely, regardless of baseline cholesterol levels. 1

• Mechanism: HMG-CoA reductase inhibition reducing cholesterol synthesis, stabilizing atherosclerotic plaques, anti-inflammatory effects
• Target: LDL-C <1.8 mmol/L (70 mg/dL) OR ≥50% reduction if baseline LDL-C 1.8-3.5 mmol/L 1
• High-intensity options: Atorvastatin 40-80 mg daily, rosuvastatin 20-40 mg daily
• Clinical Application: A post-MI patient with baseline LDL 100 mg/dL should receive atorvastatin 80 mg targeting LDL <70 mg/dL

ACE Inhibitors

ACE inhibitors should be started within the first 24 hours in patients with heart failure, LVEF <40%, diabetes, or anterior infarction. 1

• Mechanism: Blocks angiotensin II formation, reducing afterload, preventing ventricular remodeling, decreasing aldosterone secretion
• Indications: All patients with LVEF <40%, heart failure, diabetes, anterior MI 1
• Broader recommendation: Consider in ALL post-MI patients regardless of blood pressure or LV function 1
• Examples: Ramipril 2.5-10 mg daily, lisinopril 2.5-20 mg daily, perindopril 4-8 mg daily
• Contraindications: Bilateral renal artery stenosis, pregnancy, angioedema history, severe hyperkalemia (K+ >5.5 mEq/L)

Angiotensin receptor blockers (ARBs), preferably valsartan, are alternatives for ACE inhibitor-intolerant patients with heart failure or LVEF <40%. 1

Mineralocorticoid Receptor Antagonists (MRAs)

MRAs (spironolactone or eplerenone) are recommended in patients with LVEF <40% AND heart failure or diabetes who are already receiving ACE inhibitor and beta-blocker, provided no renal failure or hyperkalemia. 1

• Mechanism: Aldosterone receptor blockade preventing sodium retention and myocardial fibrosis
• Dosing: Eplerenone 25-50 mg daily, spironolactone 12.5-25 mg daily
• Contraindications:
  • Creatinine >2.5 mg/dL (men) or >2.0 mg/dL (women) 1
  • Potassium >5.0 mEq/L 1
• Monitoring: Check potassium and creatinine at 3 days, 1 week, then monthly for 3 months
• Clinical Application: A post-anterior MI patient with LVEF 35%, on lisinopril and metoprolol, with K+ 4.2 and Cr 1.1 should receive eplerenone 25 mg daily

Beta-Blockers (Long-Term)

Oral beta-blockers are mandatory indefinitely in all patients with heart failure and/or LVEF <40%. 1

• Evidence-based agents: Carvedilol, metoprolol succinate, bisoprolol
• Dosing: Titrate to target or maximally tolerated dose
• Benefits: Reduces mortality, recurrent MI, and heart failure hospitalization 1
• Broader use: Continue in all post-MI patients without contraindications 1

Special Populations and Situations

Anticoagulation Indications

Oral anticoagulation (warfarin INR 2-3 or DOAC) is indicated for atrial fibrillation, LV thrombus, or mechanical valve. 1

Triple therapy (aspirin + P2Y12 inhibitor + anticoagulant) should be minimized in duration due to bleeding risk; consider bare metal stent over drug-eluting stent to shorten DAPT duration. 1

Right Ventricular Infarction

Avoid nitrates, diuretics, and morphine in RV infarction; maintain preload with IV fluids. 1

• Recognition: Inferior STEMI with ST-elevation in V4R, hypotension, clear lungs
• Management: Volume resuscitation, avoid preload-reducing agents

Cardiogenic Shock

Immediate PCI is mandatory; routine intra-aortic balloon pump is NOT indicated. 1

Risk Factor Modification

Smoking Cessation

Identify all smokers and provide repeated cessation advice with pharmacotherapy (nicotine replacement, varenicline, or bupropion) and follow-up support. 1

Cardiac Rehabilitation

Participation in cardiac rehabilitation program is recommended for all post-MI patients. 1

• Components: Supervised exercise training, risk factor modification, psychosocial support
• Benefits: Reduces mortality, improves quality of life, enhances functional capacity

Diabetes Management

Target HbA1c <6.5-7% with intensive lifestyle modification and appropriate hypoglycemic therapy. 1

Blood Pressure Control

Target BP <130/80 mmHg through lifestyle changes and pharmacotherapy. 1

Influenza Vaccination

Annual influenza immunization is recommended for all post-MI patients. 1

Common Pitfalls to Avoid

• Never give nitrates to patients with RV infarction, hypotension, or recent phosphodiesterase inhibitor use 1
• Never give IV beta-blockers to patients with acute heart failure, hypotension, or bradycardia 1
• Never use fondaparinux for primary PCI anticoagulation 1
• Never delay aspirin administration—it should be given immediately upon suspicion of MI 1
• Never use clopidogrel alone when ticagrelor or prasugrel are available and not contraindicated 1
• Never omit statin therapy regardless of baseline cholesterol levels 1
• Never forget to add PPI in high-risk patients on DAPT 1