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Omecamtiv mecarbil missed primary endpoint in ATOMIC-AHF
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AMSTERDAM — Omecamtiv mecarbil did not meet the primary endpoint of reducing dyspnea in patients with acute HF in the ATOMIC-AHF study. However, the highest dose of the novel cardiac myosin activator was associated with greater dyspnea relief compared with placebo and researchers observed a trend toward reduction of worsening HF.
The phase 2, dose-finding, randomized, double blind, sequential cohort study included patients (n=613) with left ventricular systolic dysfunction who were hospitalized for acute HF with dyspnea at rest or minimal exertion despite an IV diuretic. The patients were randomly assigned to 48 hours of IV omecamtiv mecarbil (Amgen/Cytokinetics) or placebo in three ascending-dose cohorts to achieve estimated plasma concentrations of 115 ng/mL, 230 mg/mL and 310 ng/mL, according to a press release.
The primary efficacy endpoint required improvement in dyspnea at 6, 24 and 48 hours.
John R. Teerlink, MD, professor of clinical medicine at University of California San Francisco, and director of heart failure at San Francisco Veterans Affairs Medical Center, presented the results at ESC Congress 2013.
John R. Teerlink
“Although this was a small, dose-finding study, we looked at the potential effect on dyspnea, although the trial was not powered to fully assess [this endpoint],” Teerlink said at a press conference.
Compared with pooled placebo groups, omecamtiv mecarbil showed no significant difference in dyspnea symptoms (P=.33). The primary endpoint was not met, Teerlink said. In the cohort assigned the highest omecamtiv mecarbil dose, the researchers observed a trend toward greater response compared with the paired placebo groups (51% vs. 37%; P=.03).
The secondary endpoint of improvement in worsening of HF also trended in a positive direction (P ranging from .03 to .08 with higher doses of omecamtiv mecarbil). Rates of 30-day mortality and all-cause hospitalization were comparable between the two groups, according to postrandomization adjudicated events analysis. MI was rare during the trial — three events in the placebo groups (1%) vs. seven events in the omecamtiv mecarbil groups (2.3%). There was also no evidence of proarrhythmia, with a 50% reduction in supraventricular tachyarrhythmias and no difference in ventricular tachyarrhthymias.
As observed in previous studies, omecamtiv mecarbil was associated with significant reductions in heart rate without decreasing systolic BP (P<.001).
Further analysis revealed a modest increase in cardiac troponin I in omecamtiv mecarbil-treated patients, but no evidence that this association was linked to increasing omecamtiv mecarbil concentrations.
“There were intensive evaluations of a level that has never been performed before in a clinical trial of troponin serially at multiple time points. This is a difference that probably would not have been detected by older troponin assays,” Teerlink said.
“ATOMIC-AHF met its overall objective for providing information to go forward in phase 3.” – by Katie Kalvaitis
For more information:
Teerlink JR. Hot Line IV: Late breaking trials on heart failure and acute coronary syndrome. Presented at: the European Society of Cardiology Congress; Aug. 31-Sept. 4, 2013; Amsterdam.
Disclosure: Teerlink reports research grants/consulting fees from Amgen, Corthera, Cytokinetics, Merck, Novartis, Sorbent and Trevena.