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Results of the PARALLAX trial shed light on the effects of sacubitril/valsartan (Entresto) in patients with heart failure with preserved ejection fraction.
Results of a 24-week trial presented at the European Society of Cardiology (ESC) Congress 2020 suggests sacubitril/valsartan (Entresto) could provide benefit in patients with heart failure with preserved ejection fraction (HFpEF) after meeting one of its co-primary endpoints
Results of the PARALLAX study, which was funded by Novartis Pharmaceutical Corp., indicate sacubitril/valsartan was associated with significant reductions in NT-ProBNP at 12 weeks when compared against individualized medical therapy, but found no significant difference 6-minute walk distance or other secondary end points.
“PARALLAX adds to the growing body of evidence highlighting the potential benefits of Entresto in HFpEF, a life-threatening condition that affects about 3 million people in the US and lacks approved treatments,” said David Soergel, MD, Global Head of Cardiovascular, Renal and Metabolic Drug Development at Novartis, in a statement.
Previously approved by the US Food and Drug Administration (FDA) for treatment of heart failure in patients with heart failure with reduced ejection fraction, the PARALLAX study aimed to build on previous clinical data by assessing the effects of sacubitril/valsartan in heart failure patients with an ejection fraction greater than 40%. The 24-week prospective, randomized, active-controlled, double-blind trial was designed with a pair of co-primary end points comparing the effects of sacubitril/valsartan in these patients against individual RAAS blockade.
In total, 2572 patients underwent randomization in the study—1281 to sacubitril/valsartan and 1285 to individualized medical therapy. Individualized medical therapy was defined as enlapril 10 mg, valsartan 160 mg, or placebo therapy.
For inclusion in the study, patients were required to have an ejection fraction greater than 40%, evidence of left ventricular hypertrophy or left atrial enlargement, elevated NTproBNP, and optimized treatment of comorbidities.
At 12 weeks, sacubitril/valsartan was associated with a 16% greater reduction in NT-proBNP when compared against individualized medical therapy (adjusted geometric mean ratio, 0.84; 95% CI, 0.80-0.88; P <.0001). When assessing the other co-primary endpoint of the trial, investigators found no statistically significant difference in 6-minute walk distance at week 24 (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5 m; P=.42) between the study arms. Results also indicated no statistically significant difference in change of KCCQ-23 clinical summary scores (least square means of difference, 0.52; 95% CI, -0.93 to 1.97; P=.48) or NYHA class (OR, 1.01; 95% CI, 0.75-1.37; P=.93) at week 24 between the study arms.
A post-hoc analysis of PARALLAX indicated those in the sacubitril/valsartan group had a lower risk of heart failure events over 24 weeks (HR, 0.49; 95% CI, 0.30-0.81) while a prespecified exploratory analysis suggested sacubitril/valsartan was associated with a decline in eGFR (adjusted mean difference, 1.10 mL/min/1.73 m2; 95% CI, 0.02-1.99) compared to individualized medical therapy.
The aforementioned statement from Novartis noted the US Food and Drug Administration accepted the supplemental New Drug Application for use of sacubitril/valsartan in patients with HFpEF.
For more insight into the post-hoc analysis and primary results of PARALLAX, Practical Cardiology reached out to study presenter Burkert Pieske, MD, professor of medicine and director of cardiology at Charite University Medicine, to take part in an ESC 2020 House Call.
This study, “PARALLAX: Sacubitril/Valsartan versus Individualized RAAS Blockade in Patients with HFpEF,” was presented at ESC Congress 2020.