RIVER-PCI: No Advantage to Ranolazine in Patients With Incomplete Revascularization

Routine treatment with ranolazine does not reduce the composite rate of ischemia-driven revascularization or hospitalization in patients with a history of chronic angina who have incomplete revascularization after PCI, according to a late-breaking trial presentation at TCT 2015. 

Giora Weisz, MD, of Shaare Zedek Medical Center, Tel Aviv, Israel, presented results of the RIVER-PCI trial, which was simultaneously published in The Lancet. A total of 2,619 patients with post-PCI evidence of incomplete revascularization (at least 50% stenosis) and a history of chronic angina were randomized to receive ranolazine (Ranexa, Gilead; 1,000 mg twice a day; n = 1,322) or placebo (n = 1,297) at 245 sites in 15 countries.

Almost half of patients had three-vessel disease and one-third had an untreated chronic total occlusion. The mean change in Syntax score from baseline to post-PCI was approximately 6.5 in each study arm.

After a median follow-up of 643 days, there was no difference between patients treated with ranolazine or placebo for the primary endpoint of ischemia-driven revascularization or hospitalization (Figure).

There were also similar rates of the secondary endpoints of sudden cardiac death, CV death and MI between the cohorts. Adverse event rates were consistent among multiple prespecified subgroups.

With regard to safety, there were no differences between ranolazine and placebo for the endpoints of MACE (composite of CV death, MI or stroke), all-cause mortality, stroke or transient ischemic attack. However, there was a trend toward more hospitalization for congestive HF in the ranolazine arm (P = .09).

The rates of study drug discontinuation overall (40.0% vs 35.7%; P = .006) and due to adverse events (14.3% vs 10.6%; P = .004) were higher with ranolazine than placebo.

Limiting factors 

The biggest limitation of RIVER-PCI, according to Weisz, is that the definition of incomplete revascularization “was anatomy-based with no requirement to prove ischemia.” Additionally, “antianginal medication use, other than ranolazine, was left to standards; however, most patients were on one or two additional anti-ischemic agents,” he said.

The high rate of study drug discontinuation in both arms may have also “biased the results toward the null,” Weisz explained.

Disclosures: 

• Weisz reports serving as a medical advisory board member for AngioSlide, AstraZeneca, Calore, Corindus, Medivisor, Medtronic and M.I. Medical Incentives and receiving grant/research support from AngioSlide and Corindus.