Pharmacology  ·  Cardiovascular

Newer Antianginal Agents — Beyond the Hemodynamic Levers

Ranolazine, ivabradine, and other non-hemodynamic mechanisms for refractory stable angina

• When nitrates, beta-blockers, and calcium channel blockers have all been maximized, further dose escalation is limited by bradycardia and hypotension; ranolazine and ivabradine add anti-ischemic benefit through mechanisms that do not compound these hemodynamic side effects.
• Ranolazine blocks the abnormal late sodium current that persists during ischemia, interrupting a self-reinforcing cycle of sodium and calcium overload that impairs diastolic relaxation and worsens ischemia — all without any effect on heart rate, blood pressure, or contractility.
• Ivabradine selectively blocks the funny current in the sinoatrial node, slowing spontaneous depolarization and reducing heart rate with no effect on contractility or atrioventricular conduction; because it acts only on the sinus node pacemaker, it is contraindicated in atrial fibrillation where the sinus node is no longer driving the rhythm.
• Ranolazine's primary risk is corrected QT interval prolongation; a baseline electrocardiogram is required before starting and it is contraindicated with significant baseline QT prolongation.
• Nicorandil and trimetazidine represent additional non-hemodynamic mechanisms used outside the United States — nicorandil combines potassium channel opening with a nitrate-like effect; trimetazidine shifts cardiac metabolism toward more oxygen-efficient glucose oxidation.