Heart Failure With Preserved Ejection Fraction: Current Status and Future Opportunities - Episode 15
An expert in the management of heart failure considers the importance of recent findings from the PARALLAX study.
Scott D. Solomon, MD: PARAGON-HF was a large outcomes trial, and there are a number of other smaller studies and more short-term studies that were conducted around the same time. One of these was called PARALLAX, which was a study that was requested by the German payers because they were concerned that the comparator being used in PARAGON-HF, which was valsartan, was not generalizable. They wanted to do a study to look at the comparative benefit of sacubitril/valsartan compared to whatever the patients were previously on. Meaning if they had been on an ACE [angiotensin-converting enzyme] inhibitor, it would be compared to an ACE inhibitor, and if they had been on an ARB [angiotensin 2 receptor blocker], then compared to an ARB. And if they were on nothing, then use nothing as the other arm. About 2500 patients were randomized to sacubitril/valsartan or whatever therapy they were previously on in terms of class. They were given either enalapril, valsartan, or nothing. The primary end point of this trial was a reduction in NT-proBNP [N-terminal pro-b-type natriuretic peptide], with several other end points, including a 6-minute walk, measures of quality of life, and other assessments as well.
PARALLAX showed a significant reduction in NT-proBNP, on a magnitude that was similar to what we saw in the PARAGON-HF and the PARAMOUNT trials, or maybe a bit less than those trials. PARALLAX did not show a benefit in terms of 6-minute walk and did not show a benefit in terms of measures of quality of life, which surprised us a bit because PARAGON-HF showed benefit in terms of quality of life. However, PARALLAX also showed a pretty substantial 40% to 50% reduction in heart failure events after the start of this trial. This wasn't a study that was large enough or designed specifically to look at heart failure events, but when you look at them, you see about a 50% overall reduction in those events, which is consistent with the data that we saw in PARAGON-HF. PARALLAX had some confusing results, but all in all, these data support the results we saw in the PARAGON-HF trial.