Ranolazine is an Effective and Safe Treatment of Adults with Symptomatic Premature Ventricular Contractions due to Triggered Ectopy.

Abstract

Early and delayed afterdepolarizations (EAD/DAD) cause triggered ventricular ectopy. Because ranolazine (RAN) suppresses EAD/DAD, we postulated that RAN might be effective in reducing premature ventricular contractions (PVCs). To assess the effect of RAN in patients with symptomatic PVCs due to triggered ectopy and its safety and tolerability. A total of 59 patients with symptomatic PVCs were identified from full-disclosure Holters. Doses of 500 and 1,000 mg offlabel RAN, daily, were given to 34 and 66% patients, respectively, and repeat Holters were performed prospectively during mean followup of 3.1 months. The two Holters were retrospectively compared. Congestive heart failure (CHF) was defined as symptoms including dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and fatigue, with a brain natriuretic peptide > 400. Systolic (heart failure with reduced ejection fraction) versus diastolic (heart failure with preserved ejection fraction, HFpEF) CHF depended upon an echocardiographic left ventricular ejection fraction (LVEF) at least 50% by apical two- and four-chamber Simpson's method (HFpEF). The mean age of the patients was 63 years, 60% were males, mean left ventricular ejection fraction was 60%, with 34% having coronary artery disease, 73% were hypertensive, 24% had type 2 diabetic, and 34% were on beta blockers. Upon repeat Holters at a mean of 3.1 months after initiating RAN, 95% (56/59) of the patients had their PVC count reduced as follows: 24% (14/59) had more than 90% decrease, 34% (20/59) had 71 to 90% decrease, and 17% (10/59) had 50 to 70% decrease. In the entire group, RAN reduced PVCs by 71% (mean: 13,329 to 3,837; p < 0.001). Ventricular bigeminy was reduced by 80% (4,168 to 851; p < 0.001), ventricular coupletswere reduced by 78% (374 to 81; p < 0.001), and ventricular tachycardiawas reduced by 91% (56 to 5; p < 0.001). The PVC reduction was dose dependent. Off-label RAN offers an effective and safe pharmacologic treatment for symptomatic triggered PVCs. A large, prospective randomized study is needed.