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Omecamtiv mecarbil not linked to reported MIs in ATOMIC-AHF trial
ORLANDO, Fla. — Omecamtiv mecarbil does not appear to be linked to MI, according to new findings from the ATOMIC-AHF trial.
The drug also was found to increase systolic ejection time in acute HF patients, 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, said in a presentation at the Annual Scientific Meeting of the Heart Failure Society of America.
Omecamtiv mecarbil, a novel cardiac myosin activator (Amgen/Cytokinetics), was evaluated in ATOMIC-AHF. The phase 2, dose-finding, randomized, double blind, sequential cohort study included 613 patients hospitalized for acute HF. Teerlink previously reported most of the study findings at ESC Congress 2013.
John R. Teerlink
Teerlink said although there had been some concern that seven patients assigned omecamtiv mecarbil experienced MI during the study period, compared with three assigned placebo, further investigation indicated that the drug was not likely a factor.
“These findings were reviewed by the data monitoring committee, and it was decided to continue the program without any further modifications,” he said.
The investigation focused on five patients assigned the highest dose of omecamtiv mecarbil assigned in the trial — 310 ng/mL during 48 hours — for whom MI was reported during the study period, Teerlink said.
Two patients had MIs well after omecamtiv mecarbil left their bloodstreams; one had stable troponin levels before undergoing PCI but elevated troponin levels after PCI; one had MI “purely triggered … by troponins, they did not report any other symptoms”; and one had an episode of angina with elevated troponin levels “and then was discharged without any other therapy for this,” he said during the presentation.
Teerlink also said omecamtiv mecarbil increased systolic ejection time in patients with acute HF, which he called the “pharmacologic calling card” of the drug; this was previously shown in chronic HF patients and healthy volunteers. The larger the dose of omecamtiv mecarbil, the greater the increase in systolic ejection time (P<.0001), he said. – by Erik Swain
For more information:
Teerlink JR. Late Breaking Clinical Trials. Presented at: the Annual Scientific Meeting of the Heart Failure Society of America; Sept. 22-25, 2013; Orlando, Fla.
Disclosure: The study was funded by Amgen and Cytokinetics. Teerlink reports research grants/consulting fees from Amgen, Corthera, Cytokinetics, Merck, Novartis, Sorbent and Trevena.
Perspective
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Perspective
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There is a need to develop a new inotrope to improve cardiac function without any side effects. Levosimendan (Simdax, Orion Corp.) was used in investigational fashion in the United States and failed to meet expectations. Importantly, the mechanism of action of omecamtiv mecarbil seems to be different from the existing inotropes in certain aspects. The fact that the drug improves cardiac function without an increase in heart rate and even has a mild negative chronotropic effect is very promising. Omecamtiv also seems to reduce incidental arrhythmias, which is a welcome news in light of the arrhythmogenic effect of the available inotropes.
There is obviously some concern about the fact that in previous studies and in this study, there was a signal of ischemia/MI, which may indicate, that at least in the higher doses, the drug may have an effect on myocardial oxygen consumption. It is obvious that there is a need for more information on the efficacy and safety of omecamtiv mecarbil, the good news is that more trials are presently ongoing and hopefully will lead to a large-scale clinical trial.