Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 55, Issue 12, Pages 1189-1196Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2009.09.068
Keywords
angina; myocardial infarction; natriuretic peptides; ranolazine; unstable angina
Categories
Funding
- CV Therapeutics (Palo Alto, California)
- Accumetrics
- Amgen
- AstraZeneca
- Bayer Healthcare
- Beckman-Coulter
- Biosite
- Bristol-Myers Squibb
- CV Therapeutics
- Daiichi Sankyo
- Eisai Medical Research
- Eli Lilly and Co.
- Genentech
- GlaxoSmithKline
- Integrated Therapeutics
- Johnson Johnson
- Merck and Company
- Millennium Pharmaceuticals
- Nanosphere
- Novartis Pharmaceuticals
- Nuvelo
- Ortho-Clinical Diagnostics,
- Pfizer
- Roche Diagnostics
- Sanofi-Aventis
- Sanofi-Synthelabo
- Schering-Plough
- Siemens
- Singulex
- CVT/Gilead
- OrthoClinical Diagnostics
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Objectives We designed a prospective evaluation of the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS) as part of a randomized, blinded, placebo-controlled trial. Background Ranolazine is believed to exert anti-ischemic effects by reducing myocardial sodium and calcium overload and consequently ventricular wall stress. BNP increases in response to increased wall stress and is a strong risk indicator in ACS. Methods We measured plasma BNP in all available baseline samples (n = 4,543) among patients with non-ST-segment elevation ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. The primary end point was a composite of cardiovascular death, myocardial infarction, and recurrent ischemia. BNP elevation was defined as >80 pg/ml. Results Patients with elevated BNP (n = 1,935) were at significantly higher risk of the primary trial end point (26.4% vs. 20.4%, p < 0.0001), cardiovascular death (8.0% vs. 2.1%, p < 0.001), and myocardial infarction (10.6% vs. 5.8%, p < 0.001) at 1 year. In patients with BNP > 80 pg/ml, ranolazine reduced the primary end point (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.66 to 0.94, p = 0.009). The effect of ranolazine in patients with BNP > 80 pg/ml was directionally similar for recurrent ischemia (HR: 0.78; 95% CI: 0.62 to 0.98; p = 0.04) and cardiovascular death or myocardial infarction (HR: 0.83; 95% CI: 0.66 to 1.05, p = 0.12). There was no detectable effect in those with low BNP (p interaction value = 0.05). Conclusions Our findings indicate that ranolazine may have enhanced efficacy in high-risk patients with ACS identified by increased BNP. The interaction of biomarkers of hemodynamic stress and the effects of ranolazine warrants additional investigation. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788) (J Am Coll Cardiol 2010; 55: 1189-96) (C) 2010 by the American College of Cardiology Foundation
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