Abstract 19771: Impact of Losmapimod on Cardiovascular Death and Heart Failure After ST-Elevation Myocardial Infarction in LATITUDE TIMI-60
Introduction: Inhibition of inflammation with the p38 MAP kinase inhibitor losmapimod may reduce adverse ventricular remodeling. While losmapimod did not demonstrate overall efficacy in the randomized LATITUDE-TIMI 60 trial, a possible signal was apparent in STEMI for cardiovascular death (CVD) and heart failure (HF) hospitalization [HR (95% CI) 0.66 (0.39 - 1.11)]. In this exploratory analysis, we evaluated the effect of losmapimod on CVD and HF according to baseline risk in patients with STEMI.
Methods: A total of 865 patients with STEMI were randomized to losmapimod or placebo in the LATITUDE-TIMI 60 trial. Baseline characteristics were compared and Cox modeling with backward selection was performed to identify significant risk factors for CVD/HF. A risk score was created assigning 1 point per risk factor.
Results: Over 24 weeks of follow up, the overall rate of CVD/HF was 7.0%. After multivariable adjustment, age, hs-CRP, chronic kidney disease (CKD) defined as eGFR ≤60, and Killip class >1 were all associated with an increased risk of CVD/HF. 0-1 risk factors was considered low risk (65% of study population, event rate 3.6%), 2-4 risk factors was considered high risk (35% of study population, event rate 13.2%). The point estimates for the effect of losmapimod on the risk of CVD/HF were similar in both the low & high risk groups [HR (95% CI) 0.83 (0.35 - 2.01) and 0.57 (0.30 - 1.07)], respectively. Given the higher event rate in the latter group, the absolute risk reduction trend was 6.9% vs 0.7% in the low risk group (Figure).
Conclusions: In patients with STEMI, age, hs-CRP, CKD, and Killip class >1 were associated with increased risk of CVD/HF. Losmapimod tended to reduce CVD/HF across the spectrum of risk in patients with STEMI, with a possible trend towards greater absolute risk reduction in those at higher risk of CVD/HF. The effect of p38 MAPK inhibitor therapy on reperfusion injury and remodeling in STEMI may warrant additional study in high-risk patients.
Author Disclosures: M.G. Silverman: None. R. Glaser: Employment; Significant; Employed by GlaxoSmithKline. M.A. Cavender: Other; Modest; Personal Fees from Merck and AstraZeneca. R. Hamershock: Research Grant; Significant; From Daiichi Sankyo to TIMI. M.L. O’Donoghue: Research Grant; Modest; Eisai, Merck, and AstraZeneca. Other Research Support; Modest; Institutional support from GlaxoSmithKline. M.S. Sabatine: Research Grant; Significant; Abbott Laboratories; Amgen; AstraZeneca; Critical Diagnostics; Daiichi-Sankyo; Eisai; Gilead; GlaxoSmithKline; Intarcia; MedImmune; Merck; Novartis; Poxel; Roche Diagnostics; Sanofi-aventis; Takeda. Honoraria; Modest; Alnylam; AstraZeneca; CVS Caremark; Ionis; Merck. D.A. Morrow: Research Grant; Significant; Abbott Laboratories, Amgen, Inc.; AstraZeneca Pharmaceuticals LP; Daichii Sankyo, Inc.; Eisai Co., Ltd, GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C, Eli Lilly and Co, Amgen, AstraZeneca, Daiichi Sankyo Co Ltd, GlaxoSmithKline, Merck and Co, Novartis Pharmaceuticals, Roche Diagnostics, Takeda. Consultant/Advisory Board; Modest; Abbott Laboratories, DiaDexus, Eli Lilly and Co, Gilead, Merck, Roche Diagnostics, GlaxoSmithKline.
- © 2016 by American Heart Association, Inc.