Ranolazine is a novel anti-anginal medication that operates via late sodium channel blockade, reducing intracellular calcium during ischemia.  Prior studies suggest ranolazine is effective in reducing the symptoms of angina among patients with ischemic heart disease.  Although revascularization is often used to address symptoms, incomplete revascularization with residual ischemic symptoms is common.  In the current study, the investigators evaluated ranolazine versus placebo in post-PCI patients with incomplete revascularization on the rates of ischemia-driven revascularization or hospitalization.  The investigators enrolled 2651 patients into this trial, randomizing to ranolazine or placebo within 14 days of the index percutaneous intervention.  Patients were included if they had a history of angina and underwent PCI, but were incompletely revascularized (>50% stenosis in at least one lesion in an epicardial vessel greater than 2.0mm in diameter).  The investigators measured time to ischemia-driven revascularization or hospitalization from randomization, as well as endpoints of time to sudden cardiac death, cardiovascular death or myocardial infarction.  After a median follow-up of 643 days, there was no significant difference between placebo and ranolazine for the primary endpoint (hazard ratio 0.95, 95% confidence interval 0.82 – 1.10), or for rates of ischemia-driven or hospitalization.  Results were similar across subgroups, including patients with acute coronary syndromes and those without.  There were higher rates of discontinuation of ranolazine than placebo because of adverse events (14 vs. 11%, p=0.04).

Conclusions: Ranolazine was no more effective than placebo in the prevention of ischemia driven revascularization or hospitalization among patients with chronic angina undergoing incomplete revascularization.  These findings raise questions about the relative efficacy of ranolazine to meaningfully improve symptoms among patients with ischemic heart disease.

Summarized by Javier A. Valle and Steven M. Bradley

Ranolazine in patients with incomplete revascularization after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomized, double-blind placebo-controlled trial.  Weisz et al. Lancet 2016; 387: 136-145