Abstract | OBJECTIVES: 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:
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Authors | David A Morrow, Benjamin M Scirica, Marc S Sabatine, James A de Lemos, Sabina A Murphy, Petr Jarolim, Pierre Theroux, Christophe Bode, Eugene Braunwald |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 55
Issue 12
Pg. 1189-1196
(Mar 23 2010)
ISSN: 1558-3597 [Electronic] United States |
PMID | 20298924
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Acetanilides
- Biomarkers
- Enzyme Inhibitors
- Piperazines
- Natriuretic Peptide, Brain
- Ranolazine
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Topics |
- Acetanilides
(pharmacology)
- Acute Coronary Syndrome
(diagnosis, drug therapy)
- Aged
- Biomarkers
(blood)
- Double-Blind Method
- Enzyme Inhibitors
(pharmacology)
- Female
- Humans
- Male
- Middle Aged
- Natriuretic Peptide, Brain
(blood)
- Piperazines
(pharmacology)
- Ranolazine
- Risk Factors
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