 |
|
JAMA-EXPRESS
Effects of Ranolazine on Recurrent Cardiovascular Events in Patients With Non–ST-Elevation Acute Coronary SyndromesThe 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.
Trial Registration clinicaltrials.gov Identifier: NCT00099788
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).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Does Ranolazine Have a Place in the Treatment of Acute Coronary Syndromes?
L. Kristin Newby and Eric D. Peterson
JAMA. 2007;297(16):1823-1825.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias induced by ischemia and ischemia-reperfusion
Dhalla et al.
Am. J. Physiol. Heart Circ. Physiol. 2009;297:H1923-H1929.
ABSTRACT
| FULL TEXT
Acute Coronary Syndromes: Diagnosis and Management, Part I
Kumar and Cannon
Mayo Clin Proc. 2009;84:917-938.
ABSTRACT
| FULL TEXT
Economic Impact of Angina After an Acute Coronary Syndrome: Insights From the MERLIN-TIMI 36 Trial
Arnold et al.
Circ Cardiovasc Qual Outcomes 2009;2:344-353.
ABSTRACT
| FULL TEXT
Ranolazine as an Adjunct to Cardioplegia: A Potential New Therapeutic Application
Hwang et al.
J CARDIOVASC PHARMACOL THER 2009;14:125-133.
ABSTRACT
Efficacy of ranolazine in patients with chronic angina observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial.
Wilson et al.
J Am Coll Cardiol 2009;53:1510-1516.
ABSTRACT
| FULL TEXT
Ischemia Detected on Continuous Electrocardiography After Acute Coronary Syndrome: Observations From the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) Trial
Scirica et al.
J Am Coll Cardiol 2009;53:1411-1421.
ABSTRACT
| FULL TEXT
Evaluation of the Glycometabolic Effects of Ranolazine in Patients With and Without Diabetes Mellitus in the MERLIN-TIMI 36 Randomized Controlled Trial
Morrow et al.
Circulation 2009;119:2032-2039.
ABSTRACT
| FULL TEXT
Regulation of Intracellular and Mitochondrial Sodium in Health and Disease
Murphy and Eisner
Circ. Res. 2009;104:292-303.
ABSTRACT
| FULL TEXT
Cardiovascular therapies and associated glucose homeostasis: implications across the dysglycemia continuum.
Cooper-DeHoff et al.
J Am Coll Cardiol 2009;53:S28-S34.
ABSTRACT
| FULL TEXT
Effects of Ranolazine on Disease-Specific Health Status and Quality of Life Among Patients With Acute Coronary Syndromes: Results from the MERLIN-TIMI 36 Randomized Trial
Arnold et al.
Circ Cardiovasc Qual Outcomes 2008;1:107-115.
ABSTRACT
| FULL TEXT
The Year in Review of Clinical Cardiac Electrophysiology
Scheinman and Keung
J Am Coll Cardiol 2008;51:2075-2081.
FULL TEXT
Is ranolazine an antiarrhythmic drug?
Eckhardt et al.
Am. J. Physiol. Heart Circ. Physiol. 2008;294:H1989-H1991.
FULL TEXT
Insulin-Resistant Cardiomyopathy: Clinical Evidence, Mechanisms, and Treatment Options
Witteles and Fowler
J Am Coll Cardiol 2008;51:93-102.
ABSTRACT
| FULL TEXT
Effect of Ranolazine, an Antianginal Agent With Novel Electrophysiological Properties, on the Incidence of Arrhythmias in Patients With Non ST-Segment Elevation Acute Coronary Syndrome: Results From the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) Randomized Controlled Trial
Scirica et al.
Circulation 2007;116:1647-1652.
ABSTRACT
| FULL TEXT
The Year in Non ST-Segment Elevation Acute Coronary Syndrome
Giugliano and Braunwald
J Am Coll Cardiol 2007;50:1386-1395.
FULL TEXT
ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine
Anderson et al.
J Am Coll Cardiol 2007;50:e1-e157.
FULL TEXT
Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology
Authors/Task Force Members et al.
Eur Heart J 2007;28:1598-1660.
FULL TEXT
Ranolazine Does Not Alter Cardiovascular Prognosis in Patients with Angina
JWatch Emergency Med. 2007;2007:1-1.
FULL TEXT
Ranolazine in Patients with Acute Coronary Syndromes
JWatch General 2007;2007:1-1.
FULL TEXT
Does Ranolazine Have a Place in the Treatment of Acute Coronary Syndromes?
Newby and Peterson
JAMA 2007;297:1823-1825.
FULL TEXT
Ranolazine to Treat Acute Coronary Syndromes?
Journal Watch Cardiology 2007;2007:1-1.
FULL TEXT
|
