Best Practices and Treatment Options to Manage Heart Failure - Episode 16

Trials of Interest in Heart Failure

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Transcript: Deepak L. Bhatt, MD, MPH: Javed, maybe I can just ask you to quickly summarize new agents that are in the pipeline? In particular, omecamtiv mecarbil, and vericiguat, which, just a couple of days ago, there was some new data presented on and published at the ACC [American College of Cardiology].

Javed Butler, MD, MPH, MBA: These are the 2 drugs to look out for. Besides all of the interest in SGLT2 [sodium glucose cotransporter 2] inhibitors, omecamtiv mecarbil is a cardiac-specific myosin activator that improves the systolic ejection time. All of the phase 2 data look pretty good. There is a very, very large trial that’s ongoing right now, and my impression is that it’s pretty far advanced. We should be getting the results within the next 12 months or so, I would assume. So, this is an exciting time.

And then vericiguat was actually just presented on within the past few days in another large trial of 5000 patients with worsening heart failure. The twist here is that even with all of these other trials, there are only 2 drugs that have actually shown a benefit in clinical outcomes in a randomized controlled trial in this really high-risk group of patients who get hospitalized with worsening heart failure. But the first drug that has really shown benefit is valsartan/sacubitril. You can argue that PIONEER-HF was a smaller trial and clinical outcomes were not the primary end point—and both of those are valid outcomes. But, when you start talking about a 40% or 45% reduction in readmission rates… So I would say that’s 1 drug that has been shown to improve outcomes.

But a large outcomes trial in this population was the VICTORIA trial with vericiguat. The primary end point was cardiovascular death or heart failure hospitalization. This was statistically significant. We saw a 10% relative risk reduction. This was a very high-risk group. There was a 35% 1-year event rate, and the absolute risk reduction was 4.2%—I think. And the number needed to treat was in the 20s. So we now have a couple of therapies that can improve outcomes in the worst types of heart failure as well.

Deepak L. Bhatt, MD, MPH: Those are really fantastic thoughts.

Akshay, I think no program these days is complete without at least asking about gene therapy. Is there any role for gene therapy in heart failure?

Akshay S. Desai, MD, MPH: Not yet, Deepak. Certainly, we’ve seen a couple of valiant attempts. Most notably, we saw one of an adeno-associated viral vector to transfect the SERCA2a to patients with failing hearts. That initially showed some promise, but then in a more definitively powered trial, there was no improvement in outcomes. So although it is a therapy of the future and it may be so for a long time, I don’t think we’re quite there yet. Some of it may have to do with the fact that we don’t have as many single-gene disorders that can be rescued with gene therapy in heart failure. There are those examples, but I think as a therapy for chronic heart failure unselected, we have a lot of work to do before that’s useful.

Just before we conclude discussing the topic of guideline-directed medical therapy, this has become very complicated very fast. It used to be that most people could remember that if you had a patient who had heart failure and a low EF [ejection fraction], you would give them an ACE [angiotensin-converting enzyme] inhibitor or an ARB [angiotensin receptor blocker] and a β-blocker. Then, maybe you’d add an MRA [mineralocorticoid receptor antagonist] and then consider other therapies. But you can get most of the way there without much complexity. Now we’re talking about leveraging neprilysin inhibition, SGLT2 inhibition, potentially a soluble guanylate cyclase stimulation, and maybe selected myosin activators. Once we start to enrich the pot with that range of therapy, I think it underscores that there will need to be an evolving partnership between cardiovascular specialists, primary care physicians, and other heart failure specialists in helping to tailor regimens for patients.

I think early referral of patients with heart failure is probably something we should also underscore, not just because of this complexity and the access that subspecialists may have to trials but also because I think that we’re much better at treating heart failure in its early stages and preventing the end stage. Our therapies are getting better but are still fairly blunt instruments—like transplant and mechanical circulatory support. So, I think if we can prevent and stall progression of heart failure, we’re really doing the best by our patients.

Transcript Edited for Clarity