Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial

Butler J, Khan MS, Anker SD, et al. · Journal of Cardiac Failure

Neither dose changed left-ventricular end-systolic volume versus placebo (4 mg: difference −0.3 mL, 95% CI −4.6 to 4.0, p = 0.90; 40 mg: +2.3 mL, 95% CI −1.9 to 6.5, p = 0.28). Ejection fraction, end-diastolic volume, strain, NT-proBNP, six-minute walk distance and KCCQ score were all unchanged as well; the one exception was left atrial volume, which fell in the 4 mg arm against placebo (−4.3 mL, 95% CI −7.5 to −1.2, p = 0.008) with no matching effect at 40 mg. This is the only randomized human data at a 4 mg/day dose, and it produced no efficacy signal on the endpoints the trial was built around, while being well tolerated over 4 weeks.

Population

71 adults with stable heart failure and reduced ejection fraction

Intervention

Elamipretide 4 mg or 40 mg subcutaneous daily for 28 days

Comparator

Placebo

Limitations

Four weeks only; cardiac imaging endpoints; funded by Stealth BioTherapeutics with an employee among the authors; baseline imbalances (the 4 mg arm started with the largest ventricles, 88.5 mL against 77.7 mL in placebo). The lone significant secondary sits in the arm with the worst baseline, appears at neither the higher dose nor on any related measure, and the trial reports no adjustment for multiple comparisons.