Omecamtiv mecarbil (OM) did not achieve its primary efficacy endpoint in reducing dyspnoea in patients with acute heart failure, according to results of the ATOMIC-AHF Study released on Sept. 3 as part of the ESC Congress 2013 in Amsterdam. However, a cohort receiving the highest dose of the drug did see greater dyspnoea relief compared with placebo.

The study randomized 613 patients with left ventricular systolic dysfunction who were hospitalized for dyspnoea to receive 48 hours of intravenous placebo or one of three doses (115, 230 or 310 ng/mL) of OM. The primary endpoint was the effect on dyspnoea at six, 24 and 48 hours, with secondary endpoints of safety, tolerability, pharmacokinetics and echocardiographic indices of cardiac function.

While the overall findings from the study showed no statistically significant differences in dyspnoea symptoms with omecamtiv mecarbil compared with placebo (p=0.33 for primary endpoint), the cohort receiving 310 ng/mL of OM saw greater relief from dyspnea symptoms compared with placebo on subgroup analysis (51 percent vs. 37 percent, P=0.03), according to the study authors. Additionally, the authors noted significant dose-related and plasma concentration-related trends in response, as well as significant concentration-related increases in systolic ejection time (P<0.001). There were also trends toward reductions in worsening heart failure, reduced incidence of supraventricular arrhythmias, and no increase ventricular arrhythmias.

"None of these outcomes should be considered confirmed, since that was not the intent of the study," said John Teerlink, MD, professor of clinical medicine at the University of San Francisco and director of heart failure at the San Francisco Veterans Affairs Medical Centre, CA. "But the trends are very encouraging, especially for a trial of its size and scope."

According to Teerlink the biggest challenge to the study was managing expectations, given that OM is "probably one of the most interesting new chemical entities in cardiovascular medicine." "Physicians have struggled for decades to develop agents that improve cardiac function without increasing arrhythmias or mortality; [OM] has the potential to be such an agent," he said.

Keywords: Heart Failure, Dyspnea, Systole