Effects of Ranolazine in Patients With Chronic Angina in Patients With and Without Percutaneous Coronary Intervention for Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 Trial

Abstract

Background: Ranolazine, a piperazine derivative with anti-ischemic effects, reduces the frequency of angina and improves exercise performance in patients with chronic angina. The effects of ranolazine in patients with established ischemic heart disease and chronic angina undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) is not well described. We hypothesized that ranolazine would reduce ischemic events, regardless of revascularization.

Methods: We examined the 1-year incidence of recurrent cardiovascular (CV) events in the subgroup of patients with prior chronic angina (n = 3565) enrolled in the randomized, double-blind, placebo-controlled Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation ACS (MERLIN)-Thrombolysis In Myocardial Infarction (TIMI) 36 trial who did or did not have a PCI within 30 days of the index event.

Results: Ranolazine reduced the risk of recurrent ischemia following admission regardless of whether patients had (hazard ratio [HR], 0.69; 95% confidence interval [CI] 0.51-0.92] or did not have PCI (HR, 0.81; 95% CI, 0.66-0.99; P interaction = 0.39). CV death, myocardial infarction, and recurrent ischemia were similarly lower with ranolazine in the PCI group (HR, 0.71; 95% CI, 0.55-0.91) vs the non-PCI group (HR, 0.91; 95% CI, 0.78-1.06; P interaction = 0.10), with a nominally significant decrease in CV death (HR, 0.39; 95% CI, 0.16-0.93) in the PCI group vs no difference in the non-PCI group (HR, 1.19; 95% CI, 0.89-1.59; P interaction = 0.02).

Conclusions: In patients with chronic angina, ranolazine reduced recurrent ischemic events, regardless of whether patients did or did not receive PCI within 30 days of a non-ST-segment ACS.

Trial registration: ClinicalTrials.gov NCT00099788.

© 2015 Wiley Periodicals, Inc.

Figures

Figure 1

Flow chart. Abbreviations: NSTE ACS, non–ST‐elevation acute coronary syndrome; PCI, percutaneous coronary intervention; UA, unstable angina.

Figure 2

Primary and secondary endpoint results. The effect of ranolazine on the primary endpoints in patients with prior angina according to PCI within 30 days of randomization is shown. The primary endpoints are CVD, myocardial infarction, and recurrent ischemia. Abbreviations: CI, confidence interval; CV, cardiovascular; CVD, cardiovascular death; EP, endpoint; HR, hazard ratio; KM, Kaplan‐Meier; MI, myocardial infarction; PCI, percutaneous coronary intervention; RI, recurrent ischemia.

Figure 3

Secondary endpoint results. The effect of ranolazine on recurrent ischemia components in patients with prior angina according to PCI within 30 days of randomization is shown. Abbreviations: CI, confidence interval; hosp, hospitalization; ECG, electrocardiogram; HR, hazard ratio; KM, Kaplan‐Meier; PCI, percutaneous coronary intervention; Rec, recurrent; revasc, revascularization.