JAMA-EXPRESS
Effects of Ranolazine on Recurrent Cardiovascular Events in Patients With Non–ST-Elevation Acute Coronary Syndromes
The MERLIN-TIMI 36 Randomized Trial
David A. Morrow, MD, MPH; Benjamin M. Scirica, MD, MPH; Ewa Karwatowska-Prokopczuk, MD; Sabina A. Murphy, MPH; Andrzej Budaj, MD; Sergei Varshavsky, MD; Andrew A. Wolff, MD; Allan Skene, PhD; Carolyn H. McCabe, BS; Eugene Braunwald, MD; For the MERLIN-TIMI 36 Trial Investigators
JAMA. 2007;297:1775-1783.
Context Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS).
Objective To determine the efficacy and safety of ranolazine during long-term treatment of patients with non–ST-elevation ACS.
Design, Setting, and Patients A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007.
Main Outcome Measures The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia.
Results The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91).
Conclusions The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy.
Author Affiliations: TIMI Study Group, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass (Drs Morrow, Scirica, and Braunwald, and Mss Murphy and McCabe); CV Therapeutics, Palo Alto, Calif (Dr Karwatowska-Prokopczuk); Postgraduate Medical School, Department of Cardiology, Grochowski Hospital, Warsaw, Poland (Dr Budaj); Evidence Clinical and Pharmaceutical Research, St Petersburg, Russia (Dr Varshavsky); Cytokinetics, San Francisco, Calif (Dr Wolff); and Nottingham Clinical Research Limited, Nottingham, United Kingdom (Dr Skene).
Does Ranolazine Have a Place in the Treatment of Acute Coronary Syndromes?L. Kristin Newby and Eric D. Peterson JAMA. 2007;297:1823-1825. EXTRACT FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Does Ranolazine Have a Place in the Treatment of Acute Coronary Syndromes?Newby and PetersonJAMA 2007;297:1823-1825.FULL TEXT
Does Ranolazine Have a Place in the Treatment of Acute Coronary Syndromes?Newby and PetersonJAMA 2007;297:1823-1825.FULL TEXT
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