番茄社区

ORLANDO -- A selective cardiac myosin activator showed potential ties to improved left ventricular (LV) function and symptoms in some heart failure patients with reduced ejection fraction, according to two analyses of the COSMIC-HF study.

Diastolic volume fell from 217 mL at baseline to ~207 mL at 20 weeks for those that received omecamtiv mecarbil 25 mg twice daily followed by uptitration to 50 mg twice daily starting at week 8 (P=0.021). NT-proBNP levels also fell by ~900 pg/mL in these patients over this period (P=0.007), reported , of San Francisco Veterans Affairs Medical Center, and colleagues.

These data from their COSMIC-HF study were presented as a poster at the Heart Failure Society of America annual meeting.

"[The drug] increases the entry rate of myosin into the tightly-bound, force-producing state with actin," according to Teerlink's group. Hence, "more hands pulling on the rope" -- and increased cardiac contractility, they noted.

"Decreases in diastolic volume and in NT-proBNP during treatment accumulated over time and suggest favorable ventricular remodeling and a reduction in myocardial wall stress. These data from COSMIC-HF indicate produced a sustained effect on LV systolic function in patients with chronic heart failure with reduced ejection fraction," they wrote.

"The magnitude of cardiac effects observed in this trial may potentially translate into improvements in clinical outcomes," they suggested.

COSMIC-HF was a phase II, multicenter randomized trial that randomized patients to omecamtiv mecarbil 25 mg twice a day (n=150); 25 mg twice a day then pharmacokinetic uptitration to 50 mg twice a day starting at week 8 (n=149); or placebo (n=149).

Patients had chronic heart failure classified as New York Heart Association class II or III.

Another poster from the same group found that among patients who eventually received 50 mg omecamtiv mecarbil twice a day, those who were asymptomatic to mildly symptomatic at baseline did not make substantial gains according to their Kansas City Cardiomyopathy Questionnaire Total Symptom Score (2.7 points over placebo, 95% CI -2.2 to 7.6).

The cohort that got uptitration and started with moderate-to-severe symptoms, on the other hand, did trend toward some improvement by week 20 (6.5 points over placebo, 95% CI -1.0 to 14.0).

"Omecamtiv mecarbil could improve heart failure symptoms, particularly in patients that self-reported at least moderate symptoms at baseline," the authors suggested.