• G Michael Felker, Raymond L Benza, A Bleakley Chandler, Jeffrey D Leimberger, Michael S Cuffe, Robert M Califf, Mihai Gheorghiade, Christopher M O'Connor, and OPTIME-CHF Investigators.
• Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. felke001@mc.duke.edu
• J. Am. Coll. Cardiol. 2003 Mar 19; 41 (6): 997-1003.

ObjectivesThe goal of this study was to assess the interaction between heart failure (HF) etiology and response to milrinone in decompensated HF.BackgroundEtiology has prognostic and therapeutic implications in HF, but its relationship to response to inotropic therapy is unknown.MethodsThe Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic dysfunction and decompensated HF to receive 48 to 72 h of intravenous milrinone or placebo. The primary end point was days hospitalized from cardiovascular causes within 60 days. In a post-hoc analysis, we evaluated the interaction between response to milrinone and etiology of HF.ResultsThe primary end point was 13.0 days for ischemic patients and 11.7 days for nonischemic patients (p = 0.2). Sixty-day mortality was 11.6% for the ischemic group and 7.5% for the nonischemic group (p = 0.03). After adjustment for baseline differences, there was a significant interaction between etiology and the effect of milrinone. Milrinone-treated patients with ischemic etiology tended to have worse outcomes than those treated with placebo in terms of the primary end point (13.6 days for milrinone vs. 12.4 days for placebo, p = 0.055 for interaction) and the composite of death or rehospitalization (42% vs. 36% for placebo, p = 0.01 for interaction). In contrast, outcomes in nonischemic patients treated with milrinone tended to be improved in terms of the primary end point (10.9 vs. 12.6 days placebo) and the composite of death or rehospitalization (28% vs. 35% placebo).ConclusionsMilrinone may have a bidirectional effect based on etiology in decompensated HF. Milrinone may be deleterious in ischemic HF, but neutral to beneficial in nonischemic cardiomyopathy.

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