Scott Solomon, MD, and Alvin Chandra, MD: The PARADIGM-HF and QoL Trial

Alvin Chandra, MD: Heart failure patients tend to suffer quite significantly from heart failure disease, even when compared to patients with other chronic diseases. They've done studies where it's actually shown to be similar to patients on dialysis. There was a paper recently, also from PARADIGM, from Dr. Lewis that was published, and in this paper, he talked about how patients on sacubitril (valsartan), when compared to enalapril, showed significant improvement in overall quality of life. So our goal with this project was to dig deeper as to what is it that is improved in these patients.

Scott Solomon, MD: What we've done now is we've looked at the way people feel, the symptoms that they have, the limitations that they have, both in physical and social domains. What we found is that in virtually all of these domains, all of these questions, patients reported improvement in their limitations if they were randomized to sacubitril compared to those who were randomized to enalapril. We think this is very exciting because, in fact, most drugs that we have in heart failure that reduce morbidity and mortality, like ACE inhibitors and ARBs and beta blockers, have not really been shown to improve these measures of physical and social limitation and quality of life. So this is really the first pharmacologic therapy that shows both a reduction in morbidity and mortality and improvement in symptoms.

Alvin Chandra, MD: Basically, we were able to demonstrate that patients who were randomized to sacubitril showed improvements in almost all of the activities, about 9 out of 10. These activities ranged from jogging to doing hobbies to doing household chores, and among these activities that we have to have improved, the largest magnitude we saw was in patients who reported limitations in sexual activities. As we all know, sacubitril improves morbidity and mortality in heart failure patients with reduced ejection fraction, but now we can also tell the patients that, in activities that you care about, these physical and social activities, you may experience improvement in those things that affect you on a day-to-day basis.

Scott Solomon, MD: Now, when new drugs are introduced, we've seen over the years in cardiovascular medicine that it does take time [for these drugs to be widely used]. We saw that with beta blockers, we saw that with mineralocorticoid receptor antagonists, so part of it is that does take some time. Part of it is that we're doing something very different with this drug than we've done with almost any other drug in heart failure, which is that we're replacing a drug that patients are already on. There's a certain amount of inertia that we have to, as physicians, overcome. It takes time to replace a drug. We have to talk about it with the patient, we have to tell them about the new drug, we have to explain why, especially if they're doing OK, we're going to switch from the drug that they've been on, maybe for years, to a new one. With that said, we are seeing that the percentage of eligible patients who are getting this drug is going up. It's probably not as high as it should be. We've estimated that if all the eligible patients who should be taking this drug based on the guidelines were, we would have a substantial reduction in deaths due to heart failure.