A 58-year-old man from Delhi presents with a 3-month history of chest pain on exertion, relieved by rest. He has hypertension (BP 155/95 mmHg) and dyslipidemia. ECG shows left ventricular hypertrophy. Coronary angiography reveals 60% stenosis in the left anterior descending artery. He is started on aspirin, atorvastatin, and a beta-blocker. However, he continues to have anginal episodes 2–3 times weekly despite optimal beta-blocker dosing. Which of the following antianginal agents would be most appropriate to add for symptom relief and cardioprotection?

Explanation

## Clinical Context This patient has stable angina with inadequate symptom control on beta-blocker monotherapy. He requires a second-line antianginal agent. ## Why Long-Acting Nitrate is Correct **Key Point:** Long-acting nitrates (isosorbide mononitrate or dinitrate) are the gold-standard second-line agents in stable angina when beta-blockers alone are insufficient [cite:Harrison 21e Ch 297]. **Mechanism of Action:** 1. Nitrates cause vasodilation of epicardial coronary arteries → increased coronary blood flow 2. Reduce cardiac preload (venous dilation) → decreased left ventricular wall stress and oxygen demand 3. Improve subendocardial perfusion in the presence of stenosis **Clinical Advantages:** - Rapid symptom relief (especially sublingual forms for acute episodes) - Long-acting formulations (isosorbide mononitrate) provide sustained angina prophylaxis - Additional benefit in hypertension (BP reduction) - Cost-effective and well-tolerated - Evidence of mortality benefit in post-MI patients when combined with beta-blockers **High-Yield:** The combination of beta-blocker + long-acting nitrate is the standard two-drug regimen for stable angina [cite:KD Tripathi 8e Ch 31]. ## Why Other Options Are Suboptimal | Agent | Role in Stable Angina | Limitation | |-------|----------------------|------------| | **Immediate-release nifedipine** | Short-acting; can cause reflex tachycardia and increased myocardial oxygen demand | Not recommended as monotherapy; inferior to beta-blockers + nitrates in stable angina | | **Ivabradine** | Heart rate reduction; used when beta-blockers contraindicated or intolerant | No direct antianginal effect; second-line to beta-blockers; not first choice for add-on | | **Ranolazine** | Metabolic modulator; reduces late Na+ influx; used in refractory angina | Third-line agent; reserved for patients with inadequate symptom control on dual therapy; not first add-on | **Clinical Pearl:** Nitrate tolerance develops with continuous exposure; use of a nitrate-free interval (10–14 hours daily) prevents tolerance development.