Providing ranolazine to patients with chronic angina and incomplete revascularization after undergoing PCI did not reduce the composite end point of ischemia-driven revascularization or hospitalization without revascularization, according to a multicenter, randomized, double-blind, placebo-controlled study.
After a median follow-up period of 643 days, the composite end point occurred in 26.2 percent of patients in the ranolazine group and 28.3 percent of patients in the placebo group. Further, the individual rates of ischemia-driven revascularization and hospitalization without revascularization as well as the rates of sudden cardiac death, cardiovascular death and MI were similar between the groups.
In addition, 14 percent of patients in the ranolazine group and 11 percent of patients in the placebo group discontinued the drug because of an adverse event. Overall, 40 percent and 36 percent of patients in the ranolazine and placebo groups, respectively, discontinued the study drug during the follow-up period.
Lead author Giora Weisz, MD, chairman of cardiology at Shaare Zedek Medical Center in Jerusalem, presented the findings on Oct. 13 in a late-breaking clinical trial session at the Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in San Francisco.
Results of the RIVER-PCI trial were simultaneously published online in The Lancet. Gilead Sciences and Menarini, the manufacturers of ranolazine, funded the trial.
Ranolazine, an oral medication that reduces ischemia, is FDA-approved to treat chronic angina.
“Ranolazine as a routine treatment for patients with incomplete revascularization did not work and did not change the primary end point as compared to placebo,” Weisz said. “There were no major safety concerns with ranolazine as compared to placebo.”
Weisz noted that 17 percent to 85 percent of patients undergoing PCI have incomplete revascularization after the procedure. He added that incomplete revascularization was associated with increased rates of mortality as well as repeat hospitalization and revascularization.
Between Nov. 3, 2011, and May 27, 2013, the researchers randomized 2,651 patients at 245 centers in 15 countries in a 1:1 ratio to receive ranolazine or placebo. The groups were well balanced. The mean age was 63.4 years old, approximately 80 percent of patients were male and more than 90 percent were white.
All patients had chronic angina that occurred on at least two days between 30 days and a year before they underwent PCI. The researchers defined incomplete revascularization as the presence of at least one lesion with stenosis of 50 percent or more in diameter in a coronary artery with a reference vessel diameter of at least 2 mm.
Patients received 500 mg of ranolazine or placebo twice daily for the first seven days. After that, they received 1,000 mg twice daily. If the dose increase was not tolerated, they could receive 500 mg or temporarily stop taking the drug. Patients also received standard treatments at the discretion of the investigators, including other antianginal drugs.
Ischemia-driven revascularization point occurred in 15.3 percent of patients in the ranolazine group and 15.5 percent of patients in the placebo group, while ischemia-driven hospitalization occurred in 15.3 percent and 17.9 percent of patients, respectively.
The rates of sudden cardiac death (0.5 percent in the ranolazine group and 0.9 percent of the placebo group), cardiovascular death (1.6 percent in each group), MI (8.4 percent versus 9 percent), all-cause mortality (3.2 percent versus 2.8 percent) and stroke (1.7 percent versus 1.5 percent) were similar between the groups.
Weisz said the most common reasons for discontinuing medication were due to mild symptoms such as nausea and dizziness.