J. Butler, M. Khan, S. Anker
Feb 14, 2020
Citations
2
Influential Citations
42
Citations
Quality indicators
Journal
Journal of cardiac failure
Abstract
BACKGROUND Elamipretide, a novel mitochondrial modulating agent, improves myocardial energetics, however, it is unknown whether this mechanistic benefit translates into improved cardiac structure and function in HF with reduced ejection fraction (HFrEF). The objective of this study was to evaluate the effects of multiple subcutaneous doses of elamipretide on left ventricular end systolic volume (LVESV) assessed by cardiac magnetic resonance imaging (MRI). METHODS Seventy-one HFrEF (LVEF ≤ 40%) patients were randomized in a double-blind, placebo-controlled trial in a 1:1:1 ratio to receive either placebo, 4 mg or 40 mg elamipretide once daily for 28 consecutive days. RESULTS Mean age (SD) of the study population was 65±10 years, 24% were females, and mean EF was 31±7%. The change in LVESV from baseline to week 4 was not significantly different between elamipretide 4mg (89.4 ml to 85 ml; difference, -4.4 ml) or 40 mg (77.9 ml to 76.6 ml; difference, -1.2 ml) compared with placebo (77.7 ml to 74.6 ml; difference, -3.8 ml) [4mg versus placebo: difference of means, -0.3; 95% CI, -4.6 to 4.0; P = 0.90; and 40mg versus placebo: difference of means, 2.3; 95% CI, -1.9 to 6.5; P = 0.28]. Also, no significant differences in change in left ventricular end diastolic volume and left ventricular ejection fraction were observed between placebo and either of the elamipretide group. Rates of any study drug related adverse events were similar among the three groups. CONCLUSIONS Elamipretide was well tolerated but did not improve LVESV at 4 weeks in stable HFrEF patients compared with placebo.