What is the recommended comprehensive secondary‑prevention regimen for a patient with ischemic heart disease, including antiplatelet therapy, high‑intensity statin, beta‑blocker, ACE‑inhibitor or ARB, nitrates, and additional agents for refractory angina?

Comprehensive Secondary Prevention Regimen for Ischemic Heart Disease

All patients with ischemic heart disease should receive a multi-drug regimen consisting of: antiplatelet therapy (aspirin 75-100 mg daily or clopidogrel 75 mg daily), high-intensity statin therapy, beta-blocker, ACE inhibitor (or ARB if intolerant), with additional agents added based on specific clinical scenarios including persistent angina, heart failure, or diabetes. 1

Core Pharmacologic Regimen (All Patients)

Antiplatelet Therapy

• Aspirin 75-100 mg daily is recommended for all patients with ischemic heart disease as lifelong therapy 1, 2
• Clopidogrel 75 mg daily is the recommended alternative in patients who are aspirin-intolerant or have contraindications 1, 2
• After percutaneous coronary intervention with stenting, dual antiplatelet therapy (aspirin plus clopidogrel) is required for at least 12 months, then transition to single antiplatelet therapy indefinitely 1, 2

Statin Therapy

• High-intensity statins are recommended in all patients with ischemic heart disease regardless of baseline cholesterol levels 1
• If lipid goals are not achieved with maximum tolerated statin dose, add ezetimibe 1
• For very high-risk patients not at goal despite statin plus ezetimibe, add a PCSK9 inhibitor 1

Beta-Blockers

• Beta-blockers are essential first-line therapy for all patients with ischemic heart disease, particularly those with prior myocardial infarction, angina, or heart failure 1
• Beta-blockers should be continued for at least 6 months post-MI and indefinitely in patients with LV systolic dysfunction (LVEF <40%) 1
• Cardioselective beta-blockers without intrinsic sympathomimetic activity are preferred (metoprolol, carvedilol, bisoprolol) 1
• If beta-blockers are contraindicated or produce intolerable side effects, substitute with a non-dihydropyridine calcium channel blocker (diltiazem or verapamil), but only if there is no LV dysfunction 1

ACE Inhibitors or ARBs

• ACE inhibitors are recommended for all patients with ischemic heart disease who have: anterior MI, persistent hypertension, LV dysfunction (LVEF <40%), heart failure, or diabetes mellitus 1
• ARBs are appropriate alternatives in patients intolerant to ACE inhibitors 1
• The combination of ACE inhibitor plus ARB is not recommended due to increased adverse events without incremental benefit 1

Blood Pressure Targets

• Target blood pressure is <130/80 mmHg for all patients with ischemic heart disease 1
• In patients with LV dysfunction, consider lowering BP further to <120/80 mmHg 1
• Critical caveat: Lower diastolic BP slowly and avoid dropping DBP below 60 mmHg, as this may worsen myocardial ischemia, particularly in elderly patients with wide pulse pressures 1

Additional Agents Based on Clinical Scenario

For Persistent or Refractory Angina

• Add long-acting nitrates (isosorbide mononitrate or dinitrate) if angina persists despite adequate beta-blocker therapy 1
• If beta-blocker plus nitrate is insufficient, add a long-acting dihydropyridine calcium channel blocker (amlodipine or nifedipine) 1
• Ranolazine can be added to beta-blockers, nitrates, or calcium channel blockers for refractory angina 3
• Sublingual nitroglycerin or nitroglycerin spray should be prescribed for immediate relief of acute anginal episodes 1

For Heart Failure or LV Dysfunction (LVEF <35-40%)

• Add an aldosterone antagonist (spironolactone or eplerenone) to ACE inhibitor and beta-blocker therapy in patients with symptomatic heart failure or severe LV dysfunction 1
• Add diuretic therapy (thiazide or loop diuretic depending on severity) for patients with signs of pulmonary or systemic congestion 1
• Consider angiotensin receptor-neprilysin inhibitor (ARNI) as alternative to ACE inhibitor in patients with persistent symptoms despite optimal medical therapy 1

For Hypertension Not Controlled with Above Regimen

• Add a thiazide diuretic as the preferred fourth agent for blood pressure control 1
• Thiazide diuretics have demonstrated cardiovascular event reduction in multiple trials 1

For Atrial Fibrillation or High Thrombotic Risk

• Oral anticoagulation with a NOAC (apixaban 5 mg twice daily, dabigatran 150 mg twice daily, edoxaban 60 mg daily, or rivaroxaban 20 mg daily) is preferred over warfarin when combined with antiplatelet therapy 1
• Triple therapy (anticoagulant plus dual antiplatelet therapy) should be minimized in duration due to bleeding risk 1

Important Caveats and Pitfalls

Drug Combinations to Avoid

• Do not combine beta-blocker with non-dihydropyridine calcium channel blocker (verapamil or diltiazem) due to risk of severe bradycardia and heart failure 1
• Avoid dual antiplatelet therapy (aspirin plus clopidogrel) beyond 12 months post-stenting in patients without acute coronary syndrome, as bleeding risk outweighs benefit 1
• Do not use nitrates with phosphodiesterase-5 inhibitors (sildenafil, tadalafil) due to risk of severe hypotension 1

Monitoring Requirements

• Proton pump inhibitor co-therapy is recommended in patients receiving antiplatelet therapy who are at high risk of gastrointestinal bleeding 1
• Monitor renal function and potassium when using ACE inhibitors, ARBs, or aldosterone antagonists 1
• Assess for symptomatic hypotension, especially when titrating multiple blood pressure-lowering agents 1

Lifestyle Modifications (Essential Adjuncts)

• Smoking cessation, weight loss if appropriate, sodium restriction, regular exercise, alcohol moderation, and glycemic control in diabetics are mandatory components of the regimen 1
• Lipid management targets and diabetes control should follow national guidelines 1