The efficacy and safety of sarcomeric contractile activators in patients with reduced ejection fraction in heart failure: a network meta-analysis

Abstract

Background: Sarcomeric contractile activators are small molecules that target myocardium to increase contractility. So far, great progress has been achieved regarding their preventive actions against idiopathic heart failure. Specifically, Levosimendan, Omecamtiv mecarbil and Danicamtiv are all sarcomeric contractile activators, while, to date, direct comparative studies of these drugs in the treatment of heart failure patients with reduced ejection fraction (HFrEF) are lacking. Methods: Network meta-analysis was conducted to compare the efficacy and safety of these drugs in HFrEF patients. The primary endpoint was heart rate, and the secondary endpoints were all-cause death, dizziness, hypotension as well as cardiac failure events. Results: A total of 22 randomized controlled trials involving 11410 participants were included. Omecamtiv mecarbil was superior to placebo (1.64(1.12, 2.17)) and Levosimendan (2.96(0.39, 5.55)) in controlling heart rate. The incidence of all-cause death caused by Levosimendan was lower than placebo (0.05(-0.47, 0.58)) and Omecamtiv mecarbil (0.05(-0.48, 0.59)). The incidence of cardiac failure events caused by Levosimendan was lower than placebo (-0.19(-0.46, 0.09)) and Omecamtiv mecarbil (-0.11(-0.40, 0.18)). Conclusions: In HFrEF patients, Omecamtiv mecarbil was superior to placebo and Levosimendan in controlling heart rate. Levosimendan induced all-cause death and cardiac failure events better than placebo and Omecamtiv mecarbil in HFrEF patients.