What are the types of antianginal medications?

Types of Antianginal Medications

Antianginal medications are classified into first-line agents (β-blockers, calcium channel blockers, and short-acting nitrates) and second-line agents (long-acting nitrates, ranolazine, ivabradine, nicorandil, and trimetazidine), though no head-to-head comparisons demonstrate superiority of one over another in terms of antianginal effects. 1

First-Line Antianginal Agents

β-Blockers

• β-blockers reduce myocardial oxygen demand by decreasing heart rate, myocardial contractility, and afterload 2
• Target doses for complete antianginal effect include: bisoprolol 10 mg once daily, metoprolol CR 200 mg once daily, or atenolol 100 mg daily 3, 4
• β-blockers are the preferred first-line therapy due to mortality benefits in post-MI patients and proven efficacy in symptom control 3, 5
• Contraindicated in severe bradycardia, second or third-degree heart block without pacemaker, decompensated heart failure, and severe bronchospastic disease 5

Calcium Channel Blockers (CCBs)

• CCBs reduce myocardial demand by reducing afterload and, in some cases, heart rate, while also enhancing myocardial oxygen supply through coronary vasodilation 2
• Dihydropyridine CCBs (e.g., amlodipine, nifedipine) are preferred when β-blockers are contraindicated or not tolerated 1, 6
• Non-dihydropyridine CCBs (diltiazem, verapamil) lower heart rate and should not be combined with β-blockers due to risk of high-degree atrioventricular block 1
• Immediate-release or short-acting dihydropyridine calcium antagonists should be avoided as they can increase adverse cardiac events 3

Short-Acting Nitrates

• Sublingual or short-acting nitroglycerin is recommended for immediate symptom relief and situational prophylaxis 1, 3
• Nitrates predominantly induce vasodilation in large capacitance blood vessels, increase epicardial coronary arterial diameter and coronary collateral blood flow, and impair platelet aggregation 7
• When administered prophylactically, both sublingual tablet and spray formulations increase angina-free walking time, abolish or delay ST segment depression, and increase exercise tolerance 7
• Patients should be instructed to sit during first use to prevent hypotension 4

Second-Line Antianginal Agents

Long-Acting Nitrates

• Long-acting nitrates (e.g., isosorbide mononitrate) should be considered as add-on therapy in patients with inadequate symptom control on β-blockers and/or CCBs 1
• Nitrates combined with β-blockers provide synergistic anti-ischemic effects by blocking reflex tachycardia 5
• A nitrate-free interval each day is essential to prevent nitrate tolerance 4, 8
• Contraindicated in patients with hypotension (systolic <130 mmHg or diastolic <80 mmHg) as they may impair coronary perfusion 1

Ranolazine

• Ranolazine is an inhibitor of the late inward sodium current that does not significantly affect heart rate or blood pressure 9, 10
• Ranolazine should be considered as add-on therapy in patients with inadequate symptom control on β-blockers and/or CCBs 1
• Particularly effective for patients with microvascular angina and endothelial dysfunction 10
• Dosing: 500 mg twice daily, increased to 1000 mg twice daily based on clinical symptoms 9
• Contraindicated with strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) and CYP3A inducers (e.g., rifampin, phenobarbital) 9
• Limit dose to 500 mg twice daily when used with moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin) 9

Ivabradine

• Ivabradine is a selective heart rate-lowering agent that inhibits the If current in the sinoatrial node 1
• Preferred when heart rate is >70 bpm, particularly in patients with hypotension where β-blockers or CCBs are contraindicated 1
• Can be safely added to β-blockers when heart rate remains elevated (≥70 bpm) 1
• Combining ivabradine with diltiazem or verapamil is clearly contraindicated 1

Nicorandil

• Nicorandil may be considered as add-on therapy in patients with inadequate symptom control on β-blockers and/or CCBs 1
• Acts as both a nitrate and potassium channel opener 1
• Reserved for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic 1

Trimetazidine

• Trimetazidine is a metabolic modulator that does not exert hemodynamic effects and does not affect oxygen demand, but improves metabolic efficiency of ischemic myocytes 1
• Trimetazidine may be considered as add-on therapy in patients with inadequate symptom control on β-blockers and/or CCBs 1
• Preferred in patients with hypotension (systolic <130 mmHg or diastolic <80 mmHg) where hemodynamic agents are contraindicated 1
• Not recommended in patients with Parkinson disease, parkinsonism, other related movement disorders, or severe renal impairment (creatinine clearance <30 ml/min) 1

Critical Prescribing Considerations

Drug Selection Based on Comorbidities

High Heart Rate (>70 bpm):

• Prefer β-blockers, non-dihydropyridine CCBs (diltiazem, verapamil), or ivabradine 1
• Avoid dihydropyridine CCBs and nitrates as they may increase heart rate 1

Hypotension (systolic <130 mmHg or diastolic <80 mmHg):

• Avoid CCBs, nitrates, and β-blockers as they may impair coronary perfusion 1
• Prefer ivabradine (if heart rate elevated), ranolazine, or trimetazidine 1

Left Ventricular Dysfunction and Heart Failure:

• β-blockers are the overwhelming, evidence-based indication as they reduce both angina and cardiovascular morbidity/mortality 1
• Avoid combining β-blockers with diltiazem or verapamil due to risk of high-degree atrioventricular block 1

Important Drug Interactions and Contraindications

• Never combine β-blockers with diltiazem or verapamil due to risk of high-degree atrioventricular block 1
• Never combine ivabradine with diltiazem or verapamil 1
• Limit simvastatin to 20 mg when used with ranolazine 9
• Limit metformin to 1700 mg daily when used with ranolazine 1000 mg twice daily 9

Evidence Limitations

No head-to-head comparisons between first-choice and second-choice treatments demonstrate superiority of one over another in terms of antianginal effects 1, 11. The classification into first-line and second-line agents is based on tradition-driven beliefs and expert opinion rather than objective comparative data 1, 11.