While sacubitril/valsartan reduced N-terminal pro B-type natriuretic peptide (NT-proBNP), it did not improve functional capacity compared to individualized background therapy in patients with heart failure with preserved ejection fraction (HFpEF), according to findings from the PARALLAX trial presented at ESC Congress 2020.

Researchers led by Burkert M. Pieske, MD, FACC, from Charité University Medicine Berlin and the German Heart Centre, Berlin, randomized a total of 2,572 HFpEF patients (mean age of 73 years/51% female) to either sacubitril/valsartan or optimal individualized background therapy (enalapril, valsartan or placebo if not taking a RAS inhibitor). The mean left ventricular ejection fraction at baseline was 56%. The primary trial endpoints were: 1) change from baseline to 12 weeks in plasma NT-proBNP; and 2) change in six-minute walk distance from baseline to 24 weeks.

Overall results found that patients treated with sacubitril/valsartan showed a significant 16.4% greater reduction in NT-proBNP than those patients treated with optimal individualized medical therapy after 12 weeks (p<0.0001). However, there was no significant difference between groups in terms of improvement in six-minute walk distance at 24 weeks. Both groups saw improvements compared with baseline (mean change was 9.7 m in the sacubitril/valsartan group and 12.2 m in the individualized medical therapy group).

In other findings, quality of life improved in both groups and was better in the sacubitril/valsartan group at week four but there was no difference between groups at week 24. Additionally, serious adverse events were reported in similar proportions across both groups, except for heart failure events. Heart failure events occurred more frequently in the individualized medical therapy group and a post hoc analysis showed that sacubitril/valsartan reduced the risk for heart failure hospitalization by 50% (p=0.005). Researchers also observed a significantly lower decline in renal function at 24 weeks in the sacubitril/valsartan group. 

According to investigators, "these results are consistent with the findings from PARAGON-HF (LVEF ≥45%) and provide further evidence for the potential benefits of sacubitril/valsartan in patients with HF and mid-range or preserved ejection fraction."

"HFpEF continues to be a real challenge in terms of effective therapy," said ACC.org Editor in Chief Kim A. Eagle, MD, MACC. "Part of this may be the notion that this type of heart muscle disease has so many potential underlying mechanisms-ischemia, fibrosis, hypertrophy, inflammation, and related vascular issues. The failure of the study drug to improve functional outcomes in this trial is disappointing. We need better phenotyping and better therapeutic agents than we have right now."

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: ESC Congress, ESC20, Heart Failure, Stroke Volume

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