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The novel oral agent omecamtiv mecarbil only modestly reduced heart failure events in heart failure with reduced ejection fraction (HFrEF) atop usual therapies, researchers reported at the virtual American Heart Association meeting. These weak results led for the drug earlier this week.

In this exclusive 番茄社区 video, , heart failure section head and director of the Cardiopulmonary Exercise Testing Laboratory of Massachusetts General Hospital in Boston, discusses the many take-home points of the .

Following is a transcript of his remarks:

GALACTIC was a study, one of the larger heart failure trials, actually, ever performed; over 8,000 patients were randomized to omecamtiv mecarbil or a placebo.

The major findings of this outcomes trial was that the omecamtiv mecarbil-treated patients had an 8% reduction in heart failure event-free survival -- so either heart failure events, hospitalization, need for urgent care, or mortality. The composite endpoint was reduced by 8%, which did meet statistical significance with a P value of slightly less than 0.05.

I think there are a lot of take-home points from this trial. It's a study that was conducted with a strategy and with a drug that really is quite distinct from the other drugs that are currently available to treat patients with heart failure. There is a longstanding history of neurohormonal blockade and interventions that interact with the renin–angiotensin–aldosterone system that have shown tremendous benefit for our patients with heart failure and reduced ejection fraction.

This is an entirely distinct mechanism of action directly targeting the sarcomere of the heart, with a very cardio-specific drug that importantly does not lower blood pressure, does not interfere with your renal function, and does not raise your potassium level -- some of the issues that we often run into with heart failure patients not being able to tolerate up-titration of drugs that lower their blood pressure; this basically comes in it with a completely separate orthogonal pathway to intervene in for heart failure.

The results are what they are. They showed that there was not a decrease in mortality and the cardiovascular death was not different between the two arms, so the endpoint was driven by hospitalizations. The drug, importantly, was found to be safe.

There were some interesting subgroup analyses, which we have to interpret the trial in its overall context, although this issue of the patients that have more impaired systolic function of the heart, so the lower ejection fraction subgroup, EF less than 28%, seemed to derive the greatest benefit in the subgroup analysis compared to those that had the higher ejection fractions, which to me makes perfect sense.

You have this drug that essentially is acting to boost the performance of the heart through direct interaction with the sarcomere, and those that have the greatest impairment in the systolic function of the heart appear to be having the most to gain from this medicine. That's particularly intriguing because those are some of the same patients that you may be running out of room for some of the other medicines that improve outcomes in heart failure.

I think that, really, the by-the-book way to interpret a trial like this is to take the population in whom the drug was investigated, look at the strength of evidence, and then make a decision about whether or not you should be applying that therapy to your patients. In that context, it's really encouraging to see a positive trial, and this was a positive trial.

The strength of evidence and the magnitude of treatment was relatively modest. We know that it's not easy to have new therapies break through in the heart failure reduced-EF space. We saw it with sacubitril/valsartan, where it literally took years for there to be uptake of the drug and widespread use, despite very compelling data that encompassed both hospitalizations and mortality.

I think that it's not easy to come into the heart failure reduced-EF space with a new agent. But for those of us that take care of these patients -- that despite all the therapies that we have they still have high morbidity, and they have high mortality, and they're hospitalized frequently -- we're really eager to find new ways, new pathways, and new treatments that can potentially help these patients.

I think that the safety data was very encouraging in that it appeared that they were almost literally identical to the placebo arm in terms of a lot of the safety parameters that were looked at.

When we think about this drug compared to some other earlier forms of therapies that were designed to boost the contractility and performance of the heart, those drugs were fraught with problems in terms of risks of arrhythmias and problems with making the heart worse over time.

To have an agent that can boost cardiac performance, modestly lower natriuretic peptide levels, and did result in a modest improvement in the outcomes in this composite, it's encouraging.

It remains to be seen what happens with uptake of it in terms of changing medical practice, and there's going to be more data on the way with this drug to inform our practice.

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