Pharmacology of Drugs for Myocardial Infarction

Introduction/Overview

Myocardial infarction (MI), commonly termed a heart attack, represents a critical manifestation of acute coronary syndrome characterized by myocardial necrosis secondary to a sustained interruption of blood supply. The underlying pathophysiology typically involves the rupture or erosion of an atherosclerotic plaque, leading to platelet adhesion, activation, and aggregation, culminating in coronary artery thrombosis. The pharmacological management of MI is multifaceted, targeting the immediate restoration of coronary blood flow, prevention of thrombus extension, reduction of myocardial oxygen demand, stabilization of the infarcted area, and long-term secondary prevention. This therapeutic strategy has evolved significantly, transforming MI from a condition with high mortality to a manageable acute event with established protocols for intervention and prevention.

The clinical relevance of understanding the pharmacology of MI drugs cannot be overstated. Optimal drug selection and timing directly influence patient outcomes, including infarct size, mortality, and the incidence of complications such as heart failure, arrhythmias, and recurrent ischemic events. The integration of pharmacological therapy with mechanical reperfusion strategies like percutaneous coronary intervention (PCI) forms the cornerstone of contemporary management.

Learning Objectives

• Classify the major pharmacological agents used in the management of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), including antiplatelets, anticoagulants, thrombolytics, beta-blockers, angiotensin-converting enzyme inhibitors, and statins.
• Explain the detailed molecular and cellular mechanisms of action for each drug class, linking pharmacodynamics to their therapeutic effects in limiting infarct size, preventing reinfarction, and improving survival.
• Analyze the pharmacokinetic profiles of key agents, including routes of administration, metabolism, elimination, and how these properties inform dosing regimens in acute and chronic phases of MI management.
• Evaluate the major adverse effect profiles, contraindications, and significant drug-drug interactions associated with MI pharmacotherapy, with particular attention to bleeding risk.
• Apply knowledge of special population considerations, including renal or hepatic impairment, geriatric patients, and pregnancy, to tailor pharmacotherapeutic plans for individual patients.

Classification

Drugs utilized in the management of myocardial infarction are classified based on their primary therapeutic target within the pathophysiological cascade. A functional classification is most clinically relevant.

Reperfusion and Antithrombotic Agents

This category forms the immediate foundation of therapy, aiming to restore blood flow and prevent further thrombosis.

• Antiplatelet Agents
  • Cyclooxygenase-1 Inhibitors: Aspirin.
  • P2Y₁₂ Receptor Antagonists: Clopidogrel, prasugrel, ticagrelor.
  • Glycoprotein IIb/IIIa Receptor Antagonists: Abciximab, eptifibatide, tirofiban (primarily used during PCI).
• Anticoagulants
  • Unfractionated Heparin (UFH)
  • Low-Molecular-Weight Heparins (LMWH): Enoxaparin, dalteparin.
  • Factor Xa Inhibitors: Fondaparinux.
  • Direct Thrombin Inhibitors: Bivalirudin (used as an alternative during PCI).
• Fibrinolytic (Thrombolytic) Agents
  • Fibrin-specific: Alteplase (t-PA), reteplase (r-PA), tenecteplase (TNK-tPA).
  • Non-fibrin-specific: Streptokinase.

Myocardial Oxygen Demand Reducers and Cardioprotective Agents

These agents mitigate ischemic injury and prevent complications.

• Beta-Adrenergic Receptor Antagonists (Beta-Blockers)
  • Non-selective: Propranolol.
  • Cardioselective (β₁-selective): Metoprolol, atenolol, bisoprolol.
• Angiotensin-Converting Enzyme (ACE) Inhibitors: Lisinopril, ramipril, enalapril.
• Angiotensin II Receptor Blockers (ARBs): Valsartan, candesartan (used as an alternative in ACE inhibitor-intolerant patients).
• Aldosterone Antagonists: Spironolactone, eplerenone.

Lipid-Modifying and Atherosclerosis-Stabilizing Agents

• HMG-CoA Reductase Inhibitors (Statins): Atorvastatin, rosuvastatin, simvastatin.
• Other Lipid Agents: Ezetimibe, PCSK9 inhibitors (evolocumab, alirocumab) may be used in high-risk patients.

Adjunctive Analgesic and Anti-ischemic Agents

• Analgesics: Morphine sulfate.
• Nitrates: Nitroglycerin (sublingual, intravenous).
• Calcium Channel Blockers: Diltiazem, verapamil (used selectively, typically when beta-blockers are contraindicated).

Mechanism of Action

Antiplatelet Agents

Aspirin irreversibly acetylates a serine residue (Ser529 in human COX-1) at the active site of platelet cyclooxygenase-1 (COX-1). 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. As platelets are anucleate and cannot synthesize new enzyme, this effect lasts for the platelet’s lifespan (7-10 days).

P2Y₁₂ Receptor Antagonists (e.g., clopidogrel, prasugrel, ticagrelor) block the adenosine diphosphate (ADP) receptor subtype P2Y₁₂ on platelet surfaces. ADP binding to P2Y₁₂ is a key amplifier of platelet activation, leading to sustained aggregation and stabilization of the platelet plug. Clopidogrel and prasugrel are thienopyridine prodrugs requiring hepatic cytochrome P450-mediated bioactivation to form active metabolites that irreversibly bind the receptor. Ticagrelor is a cyclopentyltriazolopyrimidine that binds reversibly and non-competitively to the P2Y₁₂ receptor, offering faster onset and offset of action.

Glycoprotein IIb/IIIa (GP IIb/IIIa) Receptor Antagonists (e.g., abciximab, eptifibatide) target the final common pathway of platelet aggregation. The GP IIb/IIIa receptor (integrin α_IIbβ₃) undergoes a conformational change upon platelet activation, enabling it to bind fibrinogen and von Willebrand factor, which cross-link adjacent platelets. Abciximab is a monoclonal antibody fragment that binds non-competitively and with high affinity, while eptifibatide and tirofiban are small-molecule competitive inhibitors.

Anticoagulants

Unfractionated Heparin acts by binding to antithrombin III (AT III), inducing a conformational change that markedly accelerates (by approximately 1000-fold) AT III’s inhibition of several activated clotting factors, most notably thrombin (Factor IIa) and Factor Xa. Heparin’s activity is monitored via the activated partial thromboplastin time (aPTT).

Low-Molecular-Weight Heparins (e.g., enoxaparin) are derived from UFH and exhibit a greater inhibitory effect against Factor Xa relative to Factor IIa (anti-Xa:anti-IIa ratio of approximately 2:1 to 4:1). This is due to their shorter polysaccharide chains, which limit simultaneous binding to both AT III and thrombin. They offer more predictable pharmacokinetics and are typically administered subcutaneously without routine monitoring.

Fondaparinux is a synthetic pentasaccharide that selectively binds AT III, potentiating its neutralization of Factor Xa. It has no effect on thrombin activity.

Bivalirudin is a direct thrombin inhibitor, a synthetic 20-amino acid analog of hirudin. It binds reversibly to both the active site and the substrate recognition site (exosite 1) of circulating and clot-bound thrombin, directly inhibiting its proteolytic activity.

Fibrinolytic Agents

These agents catalyze the conversion of the endogenous zymogen plasminogen to the active enzyme plasmin, which degrades fibrin within a thrombus. Streptokinase, a bacterial protein, forms a 1:1 stoichiometric complex with plasminogen, inducing a conformational change that exposes its active site, allowing it to convert other plasminogen molecules to plasmin. It is non-fibrin specific, leading to systemic plasmin generation and a greater “lytic state.”

Alteplase (tissue-type plasminogen activator, t-PA) is a recombinant form of endogenous t-PA. It has a high affinity for fibrin; when bound to fibrin within a clot, its enzymatic activity in converting fibrin-bound plasminogen to plasmin is enhanced several hundred-fold. This relative fibrin specificity theoretically confines plasmin generation to the vicinity of the thrombus, although systemic effects still occur. Reteplase and tenecteplase are modified variants with longer half-lives and, in the case of tenecteplase, greater fibrin specificity and resistance to plasminogen activator inhibitor-1 (PAI-1).

Beta-Adrenergic Receptor Antagonists

By competitively blocking β₁-adrenergic receptors in the heart, these agents reduce the positive chronotropic (heart rate), inotropic (contractility), and dromotropic (conduction velocity) effects of catecholamines. This reduction in sympathetic tone decreases myocardial oxygen demand, a critical factor in the ischemic myocardium. They may also increase the threshold for ventricular fibrillation and reduce renin release from the kidneys.

Angiotensin-Converting Enzyme (ACE) Inhibitors

ACE inhibitors competitively inhibit angiotensin-converting enzyme, which is responsible for the conversion of angiotensin I to the potent vasoconstrictor angiotensin II and for the degradation of bradykinin. Reduced angiotensin II levels lead to vasodilation (reducing afterload), decreased aldosterone secretion (reducing sodium and water retention, i.e., preload), and attenuation of maladaptive cardiac remodeling. The accumulation of bradykinin contributes to vasodilation but is also implicated in the side effect of cough.

HMG-CoA Reductase Inhibitors (Statins)

Statins competitively inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in hepatic cholesterol biosynthesis. Depletion of intracellular cholesterol upregulates hepatic LDL receptor expression, increasing clearance of LDL-cholesterol from the bloodstream. Beyond lipid-lowering, statins exert pleiotropic effects believed to stabilize atherosclerotic plaques, including improving endothelial function, reducing vascular inflammation, and inhibiting platelet aggregation.

Pharmacokinetics

Antiplatelet Agents

Aspirin is rapidly absorbed in the stomach and upper small intestine. Oral bioavailability is approximately 50% due to presystemic hydrolysis. Peak plasma levels occur within 30-40 minutes. It is hydrolyzed to salicylate by esterases in the gut wall and liver; salicylate is then metabolized hepatically. Elimination follows first-order kinetics at low doses and zero-order at high anti-inflammatory doses. For antiplatelet effect, a low dose (e.g., 81 mg) is sufficient and minimizes systemic prostaglandin inhibition.

Clopidogrel is an orally administered prodrug with bioavailability of at least 50%. It undergoes extensive two-step oxidative metabolism primarily by hepatic CYP2C19, with contributions from CYP3A4 and others, to generate the active thiol metabolite. This process results in a delayed onset of action (2-6 hours). Genetic polymorphisms in CYP2C19 leading to reduced function alleles are associated with diminished platelet inhibition (“clopidogrel resistance”). The active metabolite is eliminated with a half-life of approximately 8 hours, but its irreversible binding confers a prolonged pharmacodynamic effect.

Ticagrelor is administered orally and has a bioavailability of about 36%. It is not a prodrug and is active as administered, leading to a faster onset (peak plasma concentration in 1.5-3 hours). It is metabolized primarily by CYP3A4 to an active metabolite (AR-C124910XX) which contributes to its effects. Both parent and metabolite have elimination half-lives of approximately 7-9 hours. Its reversible binding allows for a faster offset of effect compared to thienopyridines.

Anticoagulants

Unfractionated Heparin is not absorbed orally and must be administered intravenously or subcutaneously. It binds extensively to plasma proteins and endothelial cells, contributing to its variable and non-linear pharmacokinetics. It is cleared primarily by the reticuloendothelial system and has a short half-life (approximately 60 minutes with IV bolus), which is dose-dependent and prolonged in renal failure.

Enoxaparin is administered subcutaneously with a bioavailability approaching 100%. Its distribution is primarily confined to the blood volume. It is metabolized in the liver by desulfation and depolymerization and renally excreted. The elimination half-life is 4-5 hours after subcutaneous injection and is prolonged in renal impairment, necessitating dose adjustment.

Fondaparinux is administered subcutaneously with 100% bioavailability. It is not metabolized and is excreted unchanged in the urine, with a terminal half-life of 17-21 hours. Its use is contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min).

Fibrinolytic Agents

All fibrinolytic agents are administered intravenously due to their proteinaceous nature. Alteplase has a very short initial half-life of 4-5 minutes, necessitating an initial bolus followed by an infusion. It is cleared rapidly by the liver. Tenecteplase is engineered with amino acid substitutions that confer a longer half-life (approximately 20 minutes), greater fibrin specificity, and resistance to PAI-1, allowing for single-bolus administration. Streptokinase has a half-life of approximately 20 minutes, but its pharmacological effect persists longer due to the continued activity of the streptokinase-plasminogen complex. Antibodies may develop after administration, potentially reducing efficacy upon re-exposure.

Beta-Blockers

Metoprolol is available in tartrate (immediate-release) and succinate (extended-release) salts. The tartrate form is rapidly and completely absorbed but undergoes significant first-pass metabolism (bioavailability ~50%), with peak concentrations in 1-2 hours and a half-life of 3-7 hours. The succinate form provides sustained release over 24 hours. Metoprolol is metabolized extensively by CYP2D6, exhibiting polymorphism. Carvedilol is also subject to significant first-pass metabolism and is metabolized by CYP2D6 and CYP2C9; it has a half-life of 7-10 hours.

ACE Inhibitors

Lisinopril is unique among ACE inhibitors as it is not a prodrug and is active upon ingestion. Its oral bioavailability is approximately 25%, with peak plasma levels in about 7 hours. It is not metabolized and is excreted unchanged in the urine, with a half-life of 12 hours that extends significantly in renal impairment. Enalapril is a prodrug hydrolyzed in the liver to enalaprilat, the active form. This conversion delays its onset of action but prolongs its duration.

Statins

Atorvastatin is well absorbed orally, but absolute bioavailability is low (~14%) due to extensive first-pass metabolism in the gut wall and liver. It is metabolized primarily by CYP3A4 to active ortho- and parahydroxylated metabolites. Its half-life is long (approximately 14 hours), but its active metabolites have half-lives of 20-30 hours, supporting once-daily dosing. Rosuvastatin has minimal metabolism via CYP2C9; it is primarily excreted unchanged in the feces. Its half-life is approximately 19 hours.

Therapeutic Uses/Clinical Applications

The application of these agents is guided by the type of MI (STEMI vs. NSTEMI), the reperfusion strategy (primary PCI vs. fibrinolysis), and the phase of management (acute, in-hospital, long-term secondary prevention).

Acute Phase Management (First 24-48 Hours)

• Dual Antiplatelet Therapy (DAPT): Aspirin (162-325 mg chewed initially, then 81-100 mg daily) plus a P2Y₁₂ inhibitor (clopidogrel, prasugrel, or ticagrelor) is initiated immediately and continued for 6-12 months depending on stent type and bleeding risk. Prasugrel and ticagrelor are generally preferred over clopidogrel in PCI-treated patients due to more potent and predictable platelet inhibition.
• Anticoagulation: Administered alongside antiplatelet therapy for several days. UFH, enoxaparin, fondaparinux, or bivalirudin may be used, with selection influenced by reperfusion strategy, renal function, and bleeding risk.
• Reperfusion Therapy:
  • Primary PCI: The preferred method if available within 120 minutes. Pharmacotherapy supports the procedure (DAPT, anticoagulants, possibly GP IIb/IIIa inhibitors).
  • Fibrinolysis: Indicated for STEMI when primary PCI cannot be performed within 120 minutes. A fibrin-specific agent (tenecteplase, alteplase) is preferred. Must be followed by anticoagulation and transfer for coronary angiography.
• Beta-Blockers: Initiated orally within 24 hours in patients without signs of heart failure, cardiogenic shock, or other contraindications to reduce infarct size and ventricular arrhythmia risk.
• ACE Inhibitors/ARBs: Started within the first 24 hours, particularly in patients with anterior infarction, heart failure, or reduced ejection fraction (<40%).
• High-Intensity Statin Therapy: Initiated or continued at high dose (e.g., atorvastatin 80 mg, rosuvastatin 20-40 mg) regardless of baseline LDL-C.
• Analgesia: Intravenous morphine for refractory chest pain and anxiety.
• Nitrates: Sublingual or intravenous nitroglycerin for ongoing ischemic pain, hypertension, or pulmonary congestion.

In-Hospital and Long-Term Secondary Prevention

• DAPT: Continued for the recommended duration post-stenting (e.g., 6 months for drug-eluting stents in stable patients, longer for complex cases).
• Beta-Blockers, ACE Inhibitors/ARBs, High-Intensity Statins: Continued indefinitely unless contraindicated.
• Aldosterone Antagonists: Added in patients with an ejection fraction ≤40% and either symptomatic heart failure or diabetes, provided serum potassium is <5.0 mEq/L and renal function is adequate.

Adverse Effects

Antiplatelet and Anticoagulant Agents

The predominant class effect is bleeding, ranging from minor bruising and epistaxis to major gastrointestinal or intracranial hemorrhage. The risk is additive when these agents are combined. Aspirin can cause gastrointestinal irritation, ulceration, and tinnitus (with high doses). Clopidogrel may cause rash, diarrhea, and rarely thrombotic thrombocytopenic purpura (TTP). Ticagrelor is associated with dyspnea (often transient) and an increased incidence of ventricular pauses in the early phase. Prasugrel carries a black box warning for significant, sometimes fatal, bleeding; it is contraindicated in patients with a history of stroke or transient ischemic attack.

Heparins carry a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated prothrombotic disorder that is more common with UFH than LMWH. Osteoporosis can occur with long-term use. Fondaparinux has a lower risk of HIT.

Fibrinolytic Agents

The most serious adverse effect is intracranial hemorrhage, occurring in approximately 0.5-1% of patients. Risk factors include advanced age, hypertension, low body weight, and prior cerebrovascular disease. Systemic bleeding, allergic reactions (particularly with streptokinase), and reperfusion arrhythmias are also common.

Beta-Blockers

Adverse effects stem from excessive β-blockade: bradycardia, heart block, hypotension, and bronchoconstriction (especially with non-selective agents in patients with reactive airway disease). They may mask the symptoms of hypoglycemia and can exacerbate heart failure or cardiogenic shock if initiated inappropriately in unstable patients. Fatigue and sexual dysfunction are common chronic side effects.

ACE Inhibitors

Dry cough occurs in up to 20% of patients, attributed to bradykinin accumulation. Angioedema is a rare but serious, potentially life-threatening reaction. First-dose hypotension can occur, particularly in volume-depleted patients. Hyperkalemia may develop due to reduced aldosterone. Renal impairment can be precipitated, especially in patients with bilateral renal artery stenosis.

Statins

Myopathy is the most clinically significant adverse effect, ranging from benign myalgias to life-threatening rhabdomyolysis. The risk is dose-dependent and increased with concomitant use of drugs inhibiting CYP3A4 (e.g., certain antifungals, macrolide antibiotics, cyclosporine). Asymptomatic elevations in liver transaminases occur in 1-3% of patients. A small increased risk of new-onset diabetes mellitus has been observed.

Drug Interactions

Major Pharmacodynamic Interactions

• Increased Bleeding Risk: The combination of antiplatelets, anticoagulants, and NSAIDs (including COX-2 inhibitors) or selective serotonin reuptake inhibitors (SSRIs) significantly elevates the risk of major bleeding, particularly gastrointestinal hemorrhage.
• Bradycardia and Heart Block: Concomitant use of beta-blockers with non-dihydropyridine calcium channel blockers (diltiazem, verapamil), digoxin, or amiodarone can precipitate profound bradycardia or advanced heart block.

Major Pharmacokinetic Interactions

• Clopidogrel and CYP2C19 Inhibitors: Drugs like omeprazole, esomeprazole, fluvoxamine, and fluconazole inhibit CYP2C19 and can reduce the formation of clopidogrel’s active metabolite, diminishing its antiplatelet effect. Pantoprazole has a lesser effect.
• Ticagrelor and CYP3A4 Inducers/Inhibitors: Potent CYP3A4 inducers (rifampin, carbamazepine, St. John’s wort) can decrease ticagrelor levels, reducing efficacy. Strong inhibitors (ketoconazole, clarithromycin, ritonavir) can increase levels and the risk of bleeding.
• Statins and CYP3A4 Inhibitors: Atorvastatin and simvastatin metabolism is inhibited by CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, cyclosporine, HIV protease inhibitors), dramatically increasing statin plasma concentrations and the risk of myopathy/rhabdomyolysis. Rosuvastatin and pravastatin are less susceptible to this interaction.
• ACE Inhibitors and NSAIDs: NSAIDs can attenuate the antihypertensive effect of ACE inhibitors and increase the risk of renal impairment, particularly in volume-depleted or elderly patients.
• ACE Inhibitors and Potassium-Sparing Agents: Concomitant use with potassium-sparing diuretics (spironolactone, amiloride), potassium supplements, or salt substitutes containing potassium increases the risk of hyperkalemia.

Special Considerations

Pregnancy and Lactation

Acute MI in pregnancy is rare but carries high mortality. Management requires balancing maternal benefit against fetal risk. Aspirin at low dose (81 mg) may be used. Clopidogrel is classified as Category B. Beta-blockers (metoprolol, labetalol) are often used, though they may cause fetal bradycardia and growth restriction. ACE inhibitors and ARBs are contraindicated (Category D) due to fetotoxicity, including renal failure, oligohydramnios, and lung hypoplasia. Statins are contraindicated (Category X). Unfractionated heparin and enoxaparin do not cross the placenta and are preferred anticoagulants. Fibrinolytics are generally avoided due to risk of placental abruption and bleeding but may be considered in life-threatening STEMI where PCI is unavailable.

Pediatric Considerations

Myocardial infarction is exceedingly rare in children and is typically secondary to congenital anomalies, Kawasaki disease, or familial hypercholesterolemia. Pharmacological management is not standardized and is extrapolated from adult guidelines with extreme caution, requiring careful dose adjustment based on body weight and surface area.

Geriatric Considerations

Elderly patients (≥75 years) have a higher prevalence of MI, comorbidities, and altered pharmacokinetics (reduced renal/hepatic clearance, decreased lean body mass). They are at significantly increased risk for both ischemic events and bleeding complications. Dosing of renally cleared drugs (enoxaparin, fondaparinux, many ACE inhibitors) must be adjusted. Prasugrel is generally not recommended in patients ≥75 years due to bleeding risk, unless high-risk features are present. Lower initial doses of beta-blockers and ACE inhibitors may be warranted to avoid first-dose hypotension.

Renal Impairment

Renal function must be assessed before initiating therapy. Enoxaparin, fondaparinux, bivalirudin, and many ACE inhibitors require dose reduction or are contraindicated in severe renal impairment (CrCl < 30 mL/min). Unfractionated heparin may be preferred in this setting due to its non-renal clearance, though monitoring is essential. Active metabolites of clopidogrel may accumulate, but clinical significance is unclear. Ticagrelor does not require renal dose adjustment.

Hepatic Impairment

Caution is advised with drugs metabolized hepatically. Statins are generally contraindicated in active liver disease or unexplained persistent transaminase elevations. Clopidogrel, a prodrug, may have reduced activation in severe liver disease. Ticagrelor exposure is increased in cirrhosis. Dosing of heparins is not significantly altered, but monitoring for bleeding is crucial due to potential coagulopathy.

Summary/Key Points

• The pharmacological management of myocardial infarction is stratified into immediate reperfusion/antithrombotic therapy, acute cardioprotection, and long-term secondary prevention.
• Dual antiplatelet therapy (aspirin plus a P2Y₁₂ inhibitor) and parenteral anticoagulation form the antithrombotic backbone of acute management, with agent selection influenced by the reperfusion strategy (PCI vs. fibrinolysis) and patient-specific factors.
• Beta-blockers, ACE inhibitors (or ARBs), and high-intensity statins are initiated early and continued indefinitely to reduce mortality, prevent remodeling, and stabilize atherosclerotic plaque.
• The principal risk of antithrombotic and fibrinolytic therapy is bleeding, including intracranial hemorrhage. Careful assessment of bleeding versus ischemic risk is paramount in therapeutic decision-making.
• Significant drug interactions exist, particularly involving the cytochrome P450 system (e.g., clopidogrel with PPIs, statins with CYP3A4 inhibitors), which can alter efficacy or safety.
• Pharmacotherapy must be individualized for special populations, with mandatory dose adjustments for renal/hepatic impairment, and careful consideration of contraindications in pregnancy and the elderly.

Clinical Pearls

• For rapid antiplatelet effect in STEMI, have the patient chew a non-enteric coated aspirin (162-325 mg) immediately upon presentation.
• Prefer ticagrelor or prasugrel over clopidogrel for PCI-treated ACS patients, unless contraindicated by bleeding risk, cost, or need for concomitant oral anticoagulation.
• Always calculate creatinine clearance before selecting an anticoagulant; fondaparinux and enoxaparin require adjustment in renal impairment.
• Do not initiate beta-blockers intravenously in patients with signs of acute heart failure or cardiogenic shock.
• Monitor serum potassium and creatinine within 1-2 weeks after initiating an ACE inhibitor or ARB, especially in patients with renal impairment or on concomitant diuretics.
• The benefit of high-intensity statin therapy post-MI is largely independent of the baseline LDL-C level; initiate or intensify statin therapy in all patients.

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