Heart Failure With Preserved Ejection Fraction: Current Status and Future Opportunities - Episode 13
An expert physician provides an overview of the PROVE-HF trial and considers the practical implications for heart failure with reduced ejection fraction.
Scott D. Solomon, MD: I'll tell you a bit about several studies that we [at Brigham and Women’s Hospital] did that looked at the effect of sacubitril/valsartan in patients with heart failure with reduced ejection fraction on ventricular structure and function, as well as a number of other things, including natriuretic peptides and measures of quality of life.
We did 2 trials around the same time. The first was called PROVE-HF, and the other was called EVALUATE-HF, and they both enrolled patients with heart failure with reduced ejection fraction. In the PROVE-HF trial, we enrolled people who were not currently taking sacubitril/valsartan, but had heart failure with reduced injection fraction and were indicated for sacubitril/valsartan. They were switched from whatever drug they were previously on, presumably an ACE [angiotensin-converting enzyme] inhibitor or ARB [angiotensin 2 receptor blockers], to sacubitril/valsartan. They were then followed for 1 year, and the primary end point was a reduction in NT-proBNP [N-terminal pro-b-type natriuretic peptide], or natriuretic peptides. We also looked at the effect on cardiac structure and function, ventricular size and function, as well as measures of quality of life.
This was a single-arm trial, so there was no comparative group. The reason there was no comparative group is that we considered it unethical to randomize patients for more than a short period to a comparator because of the benefits that had been shown with sacubitril/valsartan in the PARADIGM-HF trial. We looked at patients over the course of the year, and they reduced their NT-proBNP quite significantly. That reduction was associated with a reduction in cardiac events: heart failure, hospitalizations, and death. We also found that they had attenuation of ventricular remodel. That is, their hearts, which started out on the larger side, became smaller, and their ejection fractions went up by a substantial amount. We believe that this therapy is working by reducing ventricular size and improving cardiac function.
We didn’t do this trial with a comparator, but we did the other study I mentioned: EVALUATE-HF. It was a 12-week study comparing sacubitril/valsartan and enalapril. It showed similar overall results and improvement in ventricular volumes, for example. Even over a short period of 12 weeks, we saw improvements in quality of life and reduction in natriuretic peptides. We put these 2 sets of data together, and we say, “There is pretty strong evidence now that this therapy is improving ventricular remodeling in patients with heart failure with reduced ejection fraction.”