RAID: Ranolazine may decrease ventricular tachycardia events

CHICAGO — In high-risk patients with implantable cardioverter defibrillators, ranolazine did not reduce the composite outcome of ventricular arrhythmic events or death but was associated with a decrease in ventricular tachycardia events requiring antitachycardia pacing, according to data from the RAID trial presented at the Heart Rhythm Society Annual Scientific Sessions.

In the NIH-funded RAID trial, 1,012 high-risk patients with ICDs were randomly assigned to placebo (n = 510) or ranolazine (Ranexa, Gilead Sciences; n = 502). Ranolazine was administered at 500 mg twice daily for 1 week and increased to 1,000 mg twice daily after 2 weeks. The mean follow-up was 28 months.

Compared with placebo, ranolazine was associated with a nonsignificant 16% reduction in the primary endpoint of ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) requiring ICD therapy or death (39.4% vs. 34.1%; HR = 0.84; 95% CI, 0.67-1.05).

Similarly, the researchers noted no significant differences between the placebo and ranolazine study arms in the incidence of prespecified secondary endpoints, including ventricular arrhythmias, ventricular arrhythmias requiring shocks, ventricular arrhythmias requiring shocks or death, or death.

However, results demonstrated a significant 27% reduction in ventricular tachycardias requiring antitachycardia pacing therapy with ranolazine vs. placebo (18% vs. 23.3%; HR = 0.73; 95% CI, 0.55-0.98).

Additionally, in an analysis of recurrent events, ranolazine was linked to a significant 35% reduction in recurrent ventricular tachycardia requiring antitachycardia pacing therapy (HR = 0.65; 95% CI, 0.45-0.93); a significant 30% reduction in risk for recurrent ventricular arrhythmias requiring shocks or antitachycardia pacing (HR = 0.7; 95% CI, 0.51-0.96); and a significant 50% reduction in recurrent inappropriate antitachycardia pacing therapy (HR = 0.5; 95% CI, 0.26-0.97).

The researchers, however, highlighted significant problems with noncompliance, with 39.6% of patients in the placebo group and 49.6% in the ranolazine group discontinuing treatment.

To account for the poor compliance, the researchers conducted an on-treatment analysis in which results associated ranolazine with a significant 25% reduction in the primary endpoint of ventricular tachycardia/ventricular arrhythmia or death (placebo, 30.9% vs. ranolazine, 21.6%; HR = 0.25; 95% CI, 0.57-0.97).

In this on-treatment analysis, the researchers also noted a significant 31% reduction in ventricular tachycardia/ventricular arrhythmia (HR = 0.69; 95% CI, 0.52-0.93) and a significant 37% reduction in ventricular tachycardia/ventricular arrhythmia requiring antitachycardia pacing therapy (HR = 0.63; 95% CI, 0.45-0.88).

“Altogether, we believe that ranolazine showed antiarrhythmic effect in our trial toward ventricular tachycardia but not ventricular fibrillation,” Wojciech Zareba, MD, PhD, of the University of Rochester Medical Center in New York, said during his presentation of the data. “Ventricular tachycardia may be a potential target for treatment.” – by Melissa Foster

Reference:

Zareba W, et al. LBCT02-01. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 10-13, 2017; Chicago.

Disclosure: Zareba reports receiving research grants from Gilead Sciences, Zoll Medical Corp. and Boston Scientific. Gilead Sciences provided ranolazine and placebo for the trial.