Ranolazine Mechanism — EECC MCQ

Correct answer: D — Ranolazine inhibits the late sodium current (INa-late) in cardiomyocytes, reducing intracellular sodium and calcium overload, which improves diastolic relaxation and reduces myocardial oxygen consumption without affecting heart rate or blood pressure

Ranolazine is a selective inhibitor of the late sodium current (INa-late). In ischaemic myocardium, the late INa is pathologically enhanced, leading to sodium overload → calcium overload (via Na⁺/Ca²⁺ exchanger operating in reverse) → impaired diastolic relaxation → increased LV wall tension → increased oxygen consumption and reduced coronary perfusion. By inhibiting INa-late, ranolazine reverses this cascade without affecting heart rate, contractility, or blood pressure. The MERLIN-TIMI 36 trial showed ranolazine reduces recurrent ischaemia in ACS. The 2024 ESC CCS Guidelines recommend ranolazine as a second-line anti-anginal (Class IIa), particularly useful in: patients unable to tolerate HR-lowering agents, those with diastolic dysfunction, and diabetic patients (it modestly reduces HbA1c). QTc prolongation is a side effect requiring monitoring.

Reference: ESC (2024): CCS Guidelines