Pharmacology of Drugs for Myocardial Infarction

1. Introduction/Overview

Myocardial infarction (MI), commonly known as a heart attack, represents a critical medical emergency characterized by the irreversible necrosis of cardiac myocytes secondary to prolonged ischemia. This event is most frequently precipitated by the acute thrombotic occlusion of a coronary artery, typically arising from the rupture or erosion of an atherosclerotic plaque. The pharmacological management of MI constitutes a cornerstone of modern cardiology, aiming to rapidly restore coronary blood flow, limit infarct size, prevent complications, and reduce long-term morbidity and mortality. The therapeutic approach is multifaceted, involving agents that address thrombosis, ischemia, neurohormonal activation, and secondary prevention. The evolution of pharmacotherapy, alongside advancements in percutaneous coronary intervention (PCI), has substantially improved clinical outcomes over recent decades.

Learning Objectives

• Classify the primary and adjunctive pharmacological agents used in the management of acute myocardial infarction and secondary prevention.
• Explain the detailed molecular and cellular mechanisms of action for each major drug class, including their effects on platelets, the coagulation cascade, hemodynamics, and cardiac remodeling.
• Analyze the pharmacokinetic profiles of key agents, including considerations for absorption, metabolism, and elimination that influence dosing regimens in acute and chronic settings.
• Evaluate the major adverse effect profiles, contraindications, and significant drug-drug interactions associated with antiplatelet agents, anticoagulants, thrombolytics, beta-blockers, angiotensin-converting enzyme inhibitors, and statins.
• Formulate appropriate therapeutic considerations for special populations, including patients with renal or hepatic impairment, the elderly, and during pregnancy or lactation.

2. Classification

The pharmacological arsenal for myocardial infarction is extensive and can be systematically categorized based on therapeutic intent and mechanism. A primary classification distinguishes between agents used in the acute management of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), and those employed for long-term secondary prevention. The following classification schema is commonly utilized.

2.1. Agents for Acute Reperfusion and Thrombosis Management

• Antiplatelet Agents
  • Cyclooxygenase-1 Inhibitors: Aspirin.
  • P2Y₁₂ Receptor Antagonists: Clopidogrel, Prasugrel, Ticagrelor.
  • Glycoprotein IIb/IIIa Receptor Antagonists: Abciximab, Eptifibatide, Tirofiban.
• Anticoagulants
  • Unfractionated Heparin (UFH).
  • Low-Molecular-Weight Heparins (LMWHs): Enoxaparin, Dalteparin.
  • Direct Thrombin Inhibitors: Bivalirudin.
  • Factor Xa Inhibitors: Fondaparinux.
• Fibrinolytic (Thrombolytic) Agents
  • Non-fibrin-specific: Streptokinase.
  • Fibrin-specific: Alteplase (t-PA), Reteplase (r-PA), Tenecteplase (TNK-tPA).

2.2. Adjunctive Agents for Acute Management

• Analgesics: Morphine sulfate.
• Anti-ischemic Agents
  • Beta-Adrenergic Receptor Antagonists (Beta-blockers): Metoprolol, Atenolol.
  • Nitrates: Nitroglycerin.
• Oxygen Therapy.

2.3. Agents for Secondary Prevention and Long-Term Management

• Dual Antiplatelet Therapy (DAPT): Aspirin plus a P2Y₁₂ inhibitor.
• Beta-Blockers: Metoprolol succinate/extended release, Carvedilol, Bisoprolol.
• Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors
  • Angiotensin-Converting Enzyme (ACE) Inhibitors: Lisinopril, Ramipril, Enalapril.
  • Angiotensin II Receptor Blockers (ARBs): Valsartan, Candesartan.
  • Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone, Eplerenone.
• Lipid-Lowering Agents
  • HMG-CoA Reductase Inhibitors (Statins): Atorvastatin, Rosuvastatin.
• Other Agents: Omega-3 fatty acids, Sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with concomitant diabetes or heart failure.

3. Mechanism of Action

3.1. Antiplatelet Agents

Aspirin (acetylsalicylic acid) irreversibly acetylates a serine residue (Ser529 in human platelets) at the active site of the cyclooxygenase-1 (COX-1) enzyme. This inhibits the conversion of arachidonic acid to prostaglandin G₂ and H₂, thereby preventing the synthesis of thromboxane A₂ (TXA₂), a potent platelet aggregator and vasoconstrictor. The effect on the platelet is irreversible for its 7-10 day lifespan.

P2Y₁₂ Receptor Antagonists block the adenosine diphosphate (ADP) receptor on platelet surfaces. Thienopyridines (Clopidogrel, Prasugrel) are prodrugs requiring hepatic cytochrome P450-mediated activation to form active metabolites that irreversibly bind to the P2Y₁₂ receptor. Ticagrelor, a cyclopentyltriazolopyrimidine, is a direct-acting, reversible antagonist that does not require metabolic activation.

Glycoprotein IIb/IIIa (GP IIb/IIIa) Antagonists inhibit the final common pathway of platelet aggregation. The GP IIb/IIIa receptor on activated platelets undergoes a conformational change to bind fibrinogen and von Willebrand factor, cross-linking adjacent platelets. Abciximab is a monoclonal antibody fragment that binds non-competitively, while Eptifibatide and Tirofiban are small molecule competitive inhibitors.

3.2. Anticoagulants

Unfractionated Heparin acts by binding to antithrombin III (AT III), inducing a conformational change that accelerates its inhibition of several activated clotting factors, most notably thrombin (Factor IIa) and Factor Xa. Its activity is monitored via the activated partial thromboplastin time (aPTT).

Low-Molecular-Weight Heparins (LMWHs) also enhance AT III activity but have a greater inhibitory effect on Factor Xa relative to thrombin (higher anti-Xa:IIa ratio) due to their shorter polysaccharide chains. They exhibit more predictable pharmacokinetics.

Fondaparinux is a synthetic pentasaccharide that selectively binds AT III, producing a conformational change that specifically potentiates the inhibition of Factor Xa.

Bivalirudin is a direct thrombin inhibitor that binds reversibly to both the active site and exosite 1 of circulating and clot-bound thrombin.

3.3. Fibrinolytic Agents

These agents catalyze the conversion of plasminogen to plasmin, which then degrades fibrin within a thrombus. Streptokinase forms a 1:1 stoichiometric complex with plasminogen, inducing a conformational change that activates other plasminogen molecules. It is non-fibrin-specific, leading to systemic plasminemia. Alteplase (tissue plasminogen activator, t-PA) is fibrin-specific; its affinity for plasminogen increases markedly in the presence of fibrin, leading to preferential activation at the thrombus site. Tenecteplase is a genetically modified t-PA with longer half-life, greater fibrin specificity, and increased resistance to plasminogen activator inhibitor-1 (PAI-1).

3.4. Beta-Adrenergic Receptor Antagonists

By competitively blocking β₁-adrenergic receptors in the heart, these agents reduce heart rate, myocardial contractility, and atrioventricular conduction velocity. This decreases myocardial oxygen demand. Additionally, by prolonging diastole, they may improve coronary perfusion. Some agents like carvedilol also possess α₁-blocking and antioxidant properties.

3.5. Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors

ACE Inhibitors inhibit the angiotensin-converting enzyme, preventing the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. They also reduce the degradation of bradykinin, a vasodilator. The net effects include vasodilation, reduced aldosterone secretion (decreasing sodium and water retention), and attenuation of adverse cardiac remodeling.

Angiotensin II Receptor Blockers (ARBs) selectively block the angiotensin II type 1 (AT₁) receptor, preventing the effects of angiotensin II regardless of its source, without affecting bradykinin metabolism.

Mineralocorticoid Receptor Antagonists (MRAs) competitively inhibit aldosterone binding in the distal nephron (promoting sodium excretion and potassium retention) and in the heart, where they exert anti-fibrotic and anti-remodeling effects.

3.6. HMG-CoA Reductase Inhibitors (Statins)

Statins competitively inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in hepatic cholesterol synthesis. This upregulates hepatic LDL receptor expression, increasing clearance of LDL-cholesterol from the circulation. Beyond lipid-lowering, statins exhibit pleiotropic effects, including improvement of endothelial function, stabilization of atherosclerotic plaques, and anti-inflammatory and anti-thrombotic properties, which are crucial in post-MI management.

4. Pharmacokinetics

4.1. Antiplatelet Agents

Aspirin is rapidly absorbed in the stomach and upper small intestine, with peak plasma concentrations (C_max) occurring within 30-40 minutes. It undergoes presystemic hydrolysis to salicylate in the gut wall and liver. Salicylate is metabolized hepatically by conjugation and oxidation, with renal excretion. The antiplatelet effect is evident within 60 minutes. Enteric-coated formulations delay absorption.

Clopidogrel is an orally administered prodrug with bioavailability of approximately 50%. It requires a two-step oxidative activation primarily by CYP2C19, with contributions from CYP3A4 and others. The active metabolite has a very short half-life (< 1 hour) but produces irreversible platelet inhibition. Onset of action is 2-6 hours after a loading dose.

Prasugrel is more efficiently metabolized than clopidogrel, with rapid hydrolysis by esterases followed by a single CYP-mediated step (primarily CYP3A4 and CYP2B6). It achieves higher and more consistent levels of the active metabolite, leading to faster and more potent platelet inhibition.

Ticagrelor is directly active and is administered orally with a bioavailability of ≈36%. It is metabolized primarily by CYP3A4 to an active metabolite (AR-C124910XX). Both parent and metabolite are eliminated via biliary and fecal routes. It has a half-life (t_1/2) of 7-9 hours and requires twice-daily dosing.

4.2. Anticoagulants

Unfractionated Heparin is not absorbed orally and must be given intravenously or subcutaneously. It binds extensively to plasma proteins and endothelial cells, leading to variable anticoagulant response and a non-linear dose-response relationship. It is cleared via a combination of rapid saturable cellular mechanisms and slower renal clearance, resulting in a dose-dependent half-life (≈60 minutes with a 100 U/kg IV bolus).

Enoxaparin, an LMWH, is administered subcutaneously with bioavailability >90%. Its anti-Xa activity exhibits predictable pharmacokinetics with a half-life of 4-5 hours, allowing for weight-based dosing without routine monitoring. It is primarily renally cleared.

Fondaparinux has 100% bioavailability after subcutaneous injection. It is not metabolized and is excreted unchanged in the urine, with a terminal half-life of 17-21 hours, permitting once-daily dosing.

Bivalirudin is administered intravenously. It is cleared proteolytically (≈80%) and renally (≈20%), with a half-life of 25 minutes in patients with normal renal function.

4.3. Fibrinolytic Agents

All fibrinolytics are administered intravenously. Alteplase has a very short initial half-life of 4-5 minutes, necessitating an initial bolus followed by an infusion. It is cleared by the liver. Tenecteplase is engineered for slower clearance and greater fibrin specificity, with a half-life of 20-24 minutes, allowing for single-bolus administration.

4.4. Beta-Blockers

Agents like metoprolol tartrate (immediate-release) are well-absorbed but undergo significant first-pass metabolism (CYP2D6), resulting in ≈50% bioavailability. The half-life is 3-7 hours. Metoprolol succinate (extended-release) provides sustained 24-hour coverage. Lipophilicity (e.g., metoprolol, propranolol) influences central nervous system penetration, while hydrophilicity (e.g., atenolol) favors renal excretion.

4.5. ACE Inhibitors and ARBs

Most ACE inhibitors (e.g., lisinopril, enalapril) are prodrugs (except lisinopril and captopril) absorbed orally. Enalapril is hydrolyzed to enalaprilat. Lisinopril is not metabolized and is excreted unchanged in urine. The half-lives vary (lisinopril: 12 hours; ramiprilat: 13-17 hours), supporting once- or twice-daily dosing. ARBs like valsartan and candesartan are active drugs with good oral bioavailability and are primarily eliminated via biliary and renal routes.

4.6. Statins

Most statins are administered orally. Atorvastatin and rosuvastatin have long half-lives (≈14 and 19 hours, respectively), allowing for once-daily dosing at any time. Atorvastatin is metabolized by CYP3A4, while rosuvastatin undergoes limited CYP2C9 metabolism. Both are substrates for hepatic uptake transporters (OATP1B1).

5. Therapeutic Uses/Clinical Applications

5.1. Acute Management of STEMI

The primary goal is rapid reperfusion via primary PCI or fibrinolysis if PCI is not available within guideline-recommended timeframes. Pharmacotherapy supports this goal:

• Dual Antiplatelet Therapy (DAPT): Aspirin (162-325 mg chewed) plus a P2Y₁₂ inhibitor (clopidogrel, prasugrel, or ticagrelor) is administered immediately. A loading dose is standard.
• Anticoagulation: UFH, enoxaparin, bivalirudin, or fondaparinux is used as an adjunct to reperfusion therapy.
• Fibrinolytics: Indicated for STEMI when primary PCI cannot be performed within 120 minutes of first medical contact. Tenecteplase is often preferred for its single-bolus administration.
• Adjunctive Therapy: Beta-blockers (oral) are initiated within 24 hours in patients without contraindications. Nitroglycerin is used for ongoing ischemia or hypertension. High-intensity statin therapy is started or continued.

5.2. Acute Management of NSTEMI

Management focuses on anti-ischemic therapy, antithrombotic therapy, and risk stratification for invasive evaluation.

• Antiplatelet Therapy: Aspirin plus a P2Y₁₂ inhibitor (clopidogrel or ticagrelor; prasugrel is reserved for PCI). GP IIb/IIIa inhibitors may be used in high-risk patients undergoing PCI.
• Anticoagulation: UFH, enoxaparin, fondaparinux, or bivalirudin is administered.
• Other Agents: Beta-blockers, nitrates, and high-intensity statins are standard.

5.3. Secondary Prevention (Long-Term Management)

Following an MI, lifelong pharmacotherapy is indicated to prevent recurrent events and mortality.

• DAPT is continued for 6-12 months depending on ischemic/bleeding risk and stent type, followed by lifelong aspirin monotherapy.
• Beta-Blockers are continued indefinitely in all patients without contraindications, particularly those with reduced left ventricular ejection fraction (LVEF).
• RAAS Inhibition: An ACE inhibitor (or ARB if intolerant) is started within 24 hours and continued indefinitely, especially in patients with anterior infarction, heart failure, or diabetes. An MRA (eplerenone or spironolactone) is added in patients with LVEF ≤40% and heart failure or diabetes, provided renal function and potassium are acceptable.
• High-Intensity Statin Therapy (e.g., atorvastatin 40-80 mg daily, rosuvastatin 20-40 mg daily) is mandatory for all patients post-MI, regardless of baseline LDL-C level, with a target LDL-C reduction of ≥50% from baseline and an absolute target < 1.8 mmol/L (< 70 mg/dL).

6. Adverse Effects

6.1. Antiplatelet and Anticoagulant Agents

The most significant adverse effect across these classes is bleeding, ranging from minor mucocutaneous bleeding to life-threatening intracranial or gastrointestinal hemorrhage. Risk is heightened with combination therapy.

• Aspirin: Gastrointestinal irritation, ulceration, and bleeding; tinnitus with high doses; Reye’s syndrome in children; hypersensitivity reactions.
• P2Y₁₂ Inhibitors: Bleeding, dyspnea (particularly with ticagrelor), bradycardia (ticagrelor), rash, diarrhea. Clopidogrel is associated with thrombotic thrombocytopenic purpura (TTP) rarely.
• Heparins: Bleeding, heparin-induced thrombocytopenia (HIT), osteoporosis with long-term use, hyperkalemia. LMWHs have a lower risk of HIT and osteoporosis.
• Fibrinolytics: Major bleeding, most concerningly intracranial hemorrhage (≈0.5-1%); reperfusion arrhythmias; allergic reactions (especially with streptokinase).

6.2. Beta-Blockers

Adverse effects are often extensions of their pharmacological action: bradycardia, heart block, hypotension, fatigue, dizziness, bronchoconstriction (contraindicated in asthma), cold extremities, and masking of hypoglycemic symptoms in diabetics. Abrupt withdrawal can precipitate rebound angina or hypertension.

6.3. RAAS Inhibitors

• ACE Inhibitors: Dry cough (due to bradykinin accumulation), angioedema (potentially life-threatening), hypotension, hyperkalemia, acute kidney injury (particularly in bilateral renal artery stenosis), rash, dysgeusia.
• ARBs: Similar to ACE inhibitors but with a significantly lower incidence of cough and angioedema.
• MRAs: Hyperkalemia (major risk), gynecomastia and sexual dysfunction (more common with spironolactone), hyponatremia, renal impairment.

6.4. Statins

Generally well-tolerated. The most common adverse effects are myalgias (muscle aches without elevated creatine kinase). More serious are myopathy (muscle pain with CK elevation) and rhabdomyolysis (rare). Hepatotoxicity (transaminase elevations) occurs infrequently. Other potential effects include new-onset diabetes mellitus (small increased risk), cognitive effects, and rarely, immune-mediated necrotizing myopathy.

6.5. Black Box Warnings

• Prasugrel: Contraindicated in patients with prior stroke or transient ischemic attack due to increased risk of intracranial hemorrhage.
• Ticagrelor: Risk of bleeding, including fatal bleeding. Aspirin maintenance doses >100 mg/day reduce its effectiveness.
• Clopidogrel (in some jurisdictions): Reduced effectiveness in poor metabolizers (CYP2C19 loss-of-function alleles).
• Statins: Risk of myopathy/rhabdomyolysis, which increases with higher doses, concomitant use with certain drugs (e.g., cyclosporine, gemfibrozil), and in elderly patients or those with renal impairment.

7. Drug Interactions

7.1. Pharmacodynamic Interactions

• Increased Bleeding Risk: Concomitant use of antiplatelets, anticoagulants, NSAIDs, SSRIs, SNRIs, and corticosteroids significantly elevates bleeding risk.
• Increased Bradycardia/Heart Block Risk: Combination of beta-blockers with non-dihydropyridine calcium channel blockers (verapamil, diltiazem), digoxin, or ivabradine.
• Hyperkalemia: ACE inhibitors/ARBs combined with MRAs, potassium supplements, potassium-sparing diuretics, NSAIDs, or trimethoprim.

7.2. Pharmacokinetic Interactions

• Clopidogrel: Proton pump inhibitors (especially omeprazole) that inhibit CYP2C19 may reduce the formation of the active metabolite. CYP2C19 inducers (rifampin) may increase activation, while strong CYP3A4 inhibitors (ketoconazole) may decrease it.
• Ticagrelor and Prasugrel: Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) increase ticagrelor exposure. Strong CYP3A4 inducers (rifampin, carbamazepine) decrease exposure to both ticagrelor and prasugrel’s active metabolite.
• Statins (especially those metabolized by CYP3A4 like atorvastatin and simvastatin): Levels are increased by CYP3A4 inhibitors (macrolides, azole antifungals, cyclosporine, amiodarone, grapefruit juice), increasing myopathy risk. Gemfibrozil inhibits glucuronidation and OATP transport, increasing risk for all statins.
• Beta-Blockers (metoprolol): CYP2D6 inhibitors (fluoxetine, quinidine) can significantly increase plasma concentrations.

7.3. Major Contraindications

• Fibrinolytics: Active internal bleeding, history of intracranial hemorrhage, ischemic stroke within 3 months, intracranial neoplasm, aortic dissection, severe uncontrolled hypertension.
• Prasugrel: Prior TIA/stroke, active pathological bleeding.
• Beta-Blockers: Acute decompensated heart failure, cardiogenic shock, severe bradycardia or heart block (2nd/3rd degree without a pacemaker), severe asthma.
• ACE Inhibitors/ARBs: Pregnancy (can cause fetal injury), history of angioedema with ACEI, bilateral renal artery stenosis.
• MRAs: Severe renal impairment (e.g., eGFR < 30 mL/min/1.73 m²), hyperkalemia.

8. Special Considerations

8.1. Pregnancy and Lactation

Acute MI during pregnancy is rare but carries high morbidity. Therapeutic choices must balance maternal benefit against fetal risk.

• Antiplatelets: Low-dose aspirin is considered safe, especially in the second and third trimesters. Clopidogrel use is limited but may be considered if essential. Prasugrel and ticagrelor data are insufficient.
• Anticoagulants: UFH and LMWHs do not cross the placenta and are preferred. Warfarin is teratogenic and contraindicated, especially in the first trimester.
• Beta-Blockers: May be used; metoprolol and labetalol are often preferred. Associated with potential fetal bradycardia, growth restriction, and neonatal hypoglycemia.
• ACE Inhibitors/ARBs/Statins: Contraindicated in pregnancy due to teratogenicity (ACEIs/ARBs cause fetal renal damage, oligohydramnios, and skull hypoplasia; statins are contraindicated).
• Lactation: Heparin and enoxaparin are not excreted in breast milk. Aspirin in low doses is likely safe, but high doses pose a risk of Reye’s syndrome. Most beta-blockers are excreted in small amounts; propranolol and metoprolol are often considered compatible.

8.2. Pediatric and Geriatric Considerations

Pediatric: MI is exceedingly rare in children, usually secondary to congenital anomalies, Kawasaki disease, or prothrombotic states. Pharmacotherapy is not standardized and is managed on a case-by-case basis, often under specialist guidance.

Geriatric: Elderly patients (≥75 years) are at higher risk for both ischemic events and bleeding complications.

• Dosing of renally cleared drugs (LMWH, fondaparinux, many ACE inhibitors) must be adjusted based on estimated glomerular filtration rate (eGFR).
• Prasugrel is generally not recommended in patients ≥75 years due to increased bleeding risk, unless high-risk features are present.
• Lower starting doses of beta-blockers and ACE inhibitors are advised (“start low, go slow”) to avoid hypotension and acute kidney injury.
• Polypharmacy increases the risk of drug interactions, particularly with antiplatelets and anticoagulants.

8.3. Renal Impairment

Renal function significantly impacts the pharmacokinetics and bleeding risk of several agents.

• Enoxaparin/Fondaparinux: Accumulate in renal impairment. Dose reduction or monitoring of anti-Xa activity is required; fondaparinux is contraindicated in severe renal impairment (CrCl < 30 mL/min).
• Bivalirudin: Requires dose reduction and infusion adjustment based on CrCl.
• GP IIb/IIIa Inhibitors: Eptifibatide and tirofiban doses must be reduced.
• ACE Inhibitors/ARBs/MRAs: Increase risk of hyperkalemia and acute kidney injury. Serum potassium and creatinine must be monitored closely; doses may need reduction or temporary withholding.
• Clopidogrel: No dose adjustment needed. Ticagrelor exposure increases in severe renal impairment but no dose adjustment is recommended.

8.4. Hepatic Impairment

Liver disease affects drug metabolism and synthesis of clotting factors, complicating antithrombotic therapy.

• Clopidogrel, Prasugrel, Ticagrelor: Metabolism may be impaired. Use with caution in severe hepatic disease due to increased bleeding risk; ticagrelor is contraindicated in severe hepatic impairment.
• Statins: Generally contraindicated in active liver disease or unexplained persistent transaminase elevations. Use with caution in chronic liver disease.
• Beta-Blockers (especially lipophilic ones): May have reduced clearance; can also mask signs of hypoglycemia and hepatic encephalopathy.
• RAAS Inhibitors: Can precipitate hypotension in cirrhosis; hyperkalemia risk may be increased.

9. Summary/Key Points

• The pharmacological management of myocardial infarction is stratified into acute reperfusion/supportive therapy and long-term secondary prevention.
• Dual antiplatelet therapy (aspirin plus a P2Y₁₂ inhibitor) and anticoagulation form the foundation of acute antithrombotic management, aiming to establish and maintain coronary patency.
• Fibrinolytic therapy is a reperfusion option for STEMI when primary PCI is not timely available, with inherent bleeding risks.
• Beta-blockers, ACE inhibitors (or ARBs), and high-intensity statins are cornerstone therapies for secondary prevention, significantly reducing mortality and recurrent events through mechanisms that extend beyond simple symptom control.
• Mineralocorticoid receptor antagonists provide additional mortality benefit in post-MI patients with reduced ejection fraction and signs of heart failure or diabetes.
• The major adverse effect across most drug classes is bleeding for antithrombotics, while other classes have distinct profiles (e.g., cough with ACE inhibitors, myopathy with statins, hyperkalemia with RAAS inhibitors).
• Careful consideration of drug interactions, contraindications, and dose adjustments in special populations (renal/hepatic impairment, elderly, pregnancy) is essential for safe and effective therapy.

Clinical Pearls

• Administer chewable aspirin for faster absorption in the acute setting.
• Avoid prasugrel in patients ≥75 years, those with low body weight (<60 kg), or a history of stroke/TIA.
• Monitor renal function and potassium closely when initiating or uptitrating ACE inhibitors/ARBs and MRAs.
• In patients with statin intolerance, even a low-dose statin provides significant cardiovascular benefit post-MI compared to none.
• The duration of DAPT requires ongoing reassessment based on individual ischemic versus bleeding risk.

References

1. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
2. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.
3. Trevor AJ, Katzung BG, Kruidering-Hall M. Katzung & Trevor's Pharmacology: Examination & Board Review. 13th ed. New York: McGraw-Hill Education; 2022.
4. Golan DE, Armstrong EJ, Armstrong AW. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 4th ed. Philadelphia: Wolters Kluwer; 2017.
5. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill Education; 2023.
6. Katzung BG, Vanderah TW. Basic & Clinical Pharmacology. 15th ed. New York: McGraw-Hill Education; 2021.
7. Rang HP, Ritter JM, Flower RJ, Henderson G. Rang & Dale's Pharmacology. 9th ed. Edinburgh: Elsevier; 2020.
8. Whalen K, Finkel R, Panavelil TA. Lippincott Illustrated Reviews: Pharmacology. 7th ed. Philadelphia: Wolters Kluwer; 2019.