Ranolazine does not lower incidence of first VT/VF, death in high-risk ICD patients
Ranolazine has failed to significantly reduce the incidence of the first ventricular tachycardia (VT) or ventricular fibrillation (VF) or death in high-risk patients with implantable cardioverter-defibrillators (ICDs), a recent study has found. However, this study is underpowered to detect a difference in the primary endpoint.
Moreover, prespecified secondary endpoint analyses reveal an association between ranolazine administration and a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality.
This double-blind, placebo-controlled clinical trial randomized high-risk ICD patients with ischaemic or nonischaemic cardiomyopathy to 1,000-mg ranolazine twice a day or placebo. VT or VF requiring appropriate ICD therapy or death, whichever occurred first, was the primary endpoint. Prespecified secondary endpoints included ICD shock for VT, VR or death and current VT or VR requiring ICD therapy.
A total of 1,012 ICD patients (mean age 64 years; 18 percent women) were included in the trial (ranolazine, n=510; placebo, n=502). The primary endpoint occurred in 372 (37 percent) patients during 28 months of follow-up. There were 270 (27 percent) VT or VF cases and 148 (15 percent) deaths.
A total of 199 (39.6 percent) patients receiving placebo and 253 (49.6 percent) patients on ranolazine discontinued treatment (p=0.001). The hazard ratio (HR) for VT, VF or death with ranolazine vs placebo was 0.84 (95 percent CI, 0.67–1.05; p=0.117).
Based on a prespecified secondary analysis, patients on ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (HR, 0.70; 0.51–0.96; p=0.028). No other significant treatment effects were noted in other prespecified secondary analyses, including components of the primary endpoint, inappropriate shocks, cardiac hospitalizations and quality of life.