RIVER-PCI Shows Ranolazine Did Not Reduce Events in Patients With Incomplete Revascularization After PCI

October 13, 2015—Findings from the RIVER-PCI trial were reported at TCT 2015, the 27th annual Transcatheter Cardiovascular Therapeutics scientific symposium of the Cardiovascular Research Foundation being held October 11–15, in San Francisco, California. The RIVER-PCI data were simultaneously published by lead investigator Giora Weisz, MD, et al online in The Lancet.

The randomized RIVER-PCI trial found that ranolazine (Ranexa; Gilead Sciences, Inc.) did not reduce the composite rate of ischemia-driven revascularization or hospitalization in patients with a history of chronic angina who had residual unrevascularized coronary artery disease after percutaneous coronary intervention (PCI). 

Ranolazine, a piperazine derivative, is a late sodium current blocker that reduces intracellular calcium overload during ischemia, and is indicated for the treatment of angina. The RIVER-PCI trial was sponsored and funded by Gilead Sciences, Inc. and The Menarini Group.

The RIVER-PCI investigators sought to determine whether intensive antianginal medical therapy can reduce the rates of adverse events among patients with post-PCI incomplete revascularization (ICR), which is associated with increased mortality and adverse cardiovascular events. 

RIVER-PCI was a multicenter, randomized, parallel-group, double-blind, placebo-controlled, event-driven trial conducted at 245 centers in 15 countries. In the study, 2,604 qualifying patients with a history of chronic angina and ICR (residual unrevascularized coronary artery disease) were randomized to ranolazine (n = 1,317) or placebo (n = 1,287). The primary efficacy endpoint was the time from randomization to the first occurrence of ischemia-driven revascularization or ischemia-driven hospitalization without revascularization.

The investigators reported that ICR was associated with high event rates. After a median follow-up of 643 days, the composite primary endpoint occurred in 345 patients assigned to ranolazine and 364 assigned to placebo (Kaplan-Meier estimates 26.2% vs 28.3% respectively; hazard ratio, 0.95; 95% confidence interval, 0.82–1.10; P = .48). The results were consistent across multiple subgroups. There were no significant differences between the two groups in the incidence of the components of the primary endpoint or major secondary endpoints including sudden cardiac death, cardiovascular death, and myocardial infarction.

Dr. Weisz commented in the TCT press release, “The results of RIVER-PCI show that the routine use of ranolazine does not reduce the composite rate of ischemia-driven revascularization or hospitalization in patients with a history of chronic angina who had ICR after PCI.” 

He added, “RIVER-PCI is the first trial to have prospectively studied patients with incomplete revascularization after PCI, and to examine the potential role of adjunctive anti-ischemic pharmacotherapy.” Dr. Weisz is Chairman of Cardiology at Shaare Zedek Medical Center in Jerusalem, Israel. He is also an Associate Professor of Medicine at Columbia University Medical Center in New York, New York.