Multicenter Controlled Trial of Novel Metabolic Active Compound (Ranolazine) in Chronic Stable Angin Patients

Ranolazine is new antianginal agent believed to reduce oxygen demand through its metabolic action without effects on blood pressure, heart rate or cardiac function. It was evaluated in randomized, double-blind, placebo-controlled, crossover trial with an extended-period Latin square design (5 one week periods). During placebo phase, 312 patients with chronic stable angin (≥3 months) receiving multiple antianginals were withdrawn from ≥1 antianginal drugs. After their exercise time had shortened by ≥1.0 mins they were randomized to receive either ranolazine 267 mg tid, 400 mg bid, 400 mg tid or placebo during each study period. After 1 week of treatment exercise tolerance (Bruce protocol) and plasm ranolazine levels were measured at peak (1 hr after dosing) and at trough (8 [tid] or 12 [bid] hr after dosing). Ranolazine significantly increased times to onset of both angin and ST segment depression at all doses tested. All exercise parameters were significantly (P ≤ 0.01) improved with ranolazine at peak plasm levels compared with placebo as ranolazine plasm levels ranged from 1,350 to 2,130 ng base/mL. No significant differences between ranolazine and placebo were observed at trough with mean ranolazine plasm levels ranging from 235 to 514 ng base/mL. No clinically meaningful hemodynamic changes or adverse events occurred with ranolazine compared with placebo. In summary, ranolazine was well tolerated over wide range of plasm levels. Ranolazine increased exercise times with no detectable effect on cardiac hemodynamics in patients with chronic stable angin taking other antianginal drugs.