TY - JOUR
T1 - Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction
T2 - The PROGRESS-HF Phase 2 Trial
AU - Butler, Jonah
AU - Khan, Muhammad Shahzeb
AU - Anker, Stefan D.
AU - Fonarow, Gregg C.
AU - Kim, Raymond J.
AU - Nodari, Savina
AU - O'Connor, Christopher M.
AU - Pieske, Burkert
AU - Pieske-Kraigher, Elisabeth
AU - Sabbah, Hani N.
AU - Senni, Michele
AU - Voors, Adriaan A.
AU - Udelson, James E.
AU - Carr, Jim
AU - Gheorghiade, Mihai
AU - Filippatos, Gerasimos
PY - 2020/5
Y1 - 2020/5
N2 - 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 heart failure (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) as assessed by cardiac magnetic resonance imaging.Methods: We randomized 71 patients with HFrEF (LVEFResults: The mean age (standard deviation) of the study population was 65 +/- 10 years, 24% were females, and the mean EF was 31% +/- 7%. The change in LVESV from baseline to week 4 was not significantly different between elamipretide 4 mg (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) (4 mg vs placebo: difference of means, -0.3; 95% CI, -4.6 to 4.0; P = 0.90; and 40 mg vs placebo: difference of means, 2.3; 95% CI, -1.9 to 6.5; P = 0.28). Also, no significant differences in change in LVESV and LVEF were observed between placebo and either of the elamipretide groups. Rates of any study drugrelated adverse events were similar in the 3 groups.Conclusions: Elamipretide was well tolerated but did not improve LVESV at 4 weeks in patients with stable HFrEF compared with placebo.
AB - 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 heart failure (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) as assessed by cardiac magnetic resonance imaging.Methods: We randomized 71 patients with HFrEF (LVEFResults: The mean age (standard deviation) of the study population was 65 +/- 10 years, 24% were females, and the mean EF was 31% +/- 7%. The change in LVESV from baseline to week 4 was not significantly different between elamipretide 4 mg (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) (4 mg vs placebo: difference of means, -0.3; 95% CI, -4.6 to 4.0; P = 0.90; and 40 mg vs placebo: difference of means, 2.3; 95% CI, -1.9 to 6.5; P = 0.28). Also, no significant differences in change in LVESV and LVEF were observed between placebo and either of the elamipretide groups. Rates of any study drugrelated adverse events were similar in the 3 groups.Conclusions: Elamipretide was well tolerated but did not improve LVESV at 4 weeks in patients with stable HFrEF compared with placebo.
KW - Mitochondria
KW - elamipretide
KW - heart failure
KW - cardiac MRI
KW - ENERGY-METABOLISM
U2 - 10.1016/j.cardfail.2020.02.001
DO - 10.1016/j.cardfail.2020.02.001
M3 - Article
VL - 26
SP - 429
EP - 437
JO - JOURNAL OF CARDIAC FAILURE
JF - JOURNAL OF CARDIAC FAILURE
SN - 1071-9164
IS - 5
ER -