Novel Heart Failure Agent Works Best in Sickest Patients

The lower the left ventricular ejection fraction (LVEF), the more the treatment effect was observed with the investigative agent omecamtiv mecarbil, according to a secondary analysis of the GALACTIC-HF trial.

The number of patients with the lowest LVEF required to treat with omecamtiv mecarbil to prevent one cardiovascular death or heart failure event was 11.8, reported John Teerlink, MD, of the University of California San Francisco and San Francisco VA Medical Center.

“The treatment effect of omecamtiv mecarbil increased with decreasing left ventricular ejection fraction,” he said at a press conference during the virtual American College of Cardiology meeting. “That’s a very important and clinically meaningful finding, particularly given that patients with low ejection fraction tend to be at the highest risk and the ones who are the most challenging to treat.”

The study was simultaneously published online in the Journal of the American College of Cardiology.

Patients in the two lowest quartiles of ejection fraction had a 15% to 17% reduction in the risk of dying from cardiovascular causes or being hospitalized with heart failure, compared with 8% for the entire patient population, Teerlink reported.

In the overall trial, treatment with omecamtiv mecarbil was associated with an 8% relative reduction in the risk of experiencing the composite primary endpoint of time to first heart failure event or cardiovascular death when compared with placebo (HR 0.92, 95% CI 0.86-0.99, P=0.025).

The trialists investigated omecamtiv mecarbil in patients with heart failure with an ejection fraction of less than or equal to 35%. This novel selective cardiac myosin activator works by improving cardiac function and structure, while decreasing heart rate and the ability for heart muscle cells to contract, and operates through a different biological pathway than any of the current heart failure medications.

In analyzing myriad subgroups in the main trial, Teerlink observed that when stratified by median LVEF — which was 28% or lower — the patients who were actually sicker got the biggest boost from the agent.

“This is a drug that will potentially help the very group of patients that are most difficult to care for,” he said. “While the results from GALACTIC-HF show omecamtiv mecarbil brought improvements overall, these new findings point to a group of patients with more severe heart failure in whom there is even greater benefit.”

An additional benefit, according to Teerlink, is that when compared with other commonly used heart failure medications, omecamtiv mecarbil did not adversely affect blood pressure, heart rate, potassium concentrations, or renal function, even when used alongside current heart failure medications. In addition, there was no increase in cardiac ischemic or ventricular arrhythmic events.

“The good news is omecamtiv mecarbil can be added on to a patient’s treatment regimen at any time, because it doesn’t interact with any of the commonly used heart failure therapies in terms of adverse effects,” Teerlink said. “While it doesn’t provide a benefit in terms of reducing cardiovascular death, it can provide its benefit in terms of reducing heart failure hospitalizations virtually anywhere in the treatment process.”

“This is very encouraging because this drug does not increase myocardial oxygen demand and it can be given in the outpatient setting if need be,” said study discussant Ileana Piña, MD, MPH, of Central Michigan University in Mount Pleasant.

“I see this as really an advancement,” Piña said at the press conference. “It didn’t change mortality. I wouldn’t expect it to change mortality because these are really, really sick patients but at least it will give you time to get the patient on the right drug. This is just very encouraging for that group of patients for whom we just scratch our heads and don’t know how to treat them,” she added.

Piña said the cardiology community has been searching for something. “How long has it been that we have been waiting for a drug to really use in this really sick population where that ejection fraction is getting lower and lower?” she asked. “These are the people we recommend for transplant and for mechanical assistance.”