PARAGON-HF: Sacubitril-Valsartan in HFpEF Patients Did Not Result in Significantly Lower Rates of Hospitalizations, Death
In patients with heart failure with preserved ejection fraction, use of the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes compared with valsartan alone, according to findings from the PARAGON-HF trial presented Sept. 1 at ESC Congress 2019.
The study, which was also published in the New England Journal of Medicine, randomly assigned 4,822 patients with heart failure and an ejection fraction of 45 percent or higher to receive sacubitril-valsartan (target doses, 97 mg of sacubitril with 103 mg of valsartan daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Researchers also assessed individual primary outcome components, secondary outcomes and safety.
Overall, 526 patients in the sacubitril-valsartan group experienced 894 primary cardiovascular events, while 557 patients in the valsartan group experienced 1,009 primary events. The incidence of death from cardiovascular causes was 8.5 percent in the sacubitril-valsartan group compared with 8.9 percent in the valsartan group. Additionally, 690 hospitalizations occurred in the sacubitril-valsartan compared with 797 in the valsartan group.
In terms of secondary outcomes, NYHA class improved in 15 percent of patients in the sacubitril-valsartan group and 12.6 percent in the valsartan group, and there was less worsening of renal function in the sacubitril-valsartan group than in the valsartan group (1.4 percent vs. 2.7 percent). Researchers also noted a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia in the sacubitril-valsartan group.
"We did not find a significant benefit of sacubitril-valsartan in patients with heart failure with preserved ejection fraction with respect to the primary composite outcome of total hospitalizations for heart failure and death from cardiovascular causes," researchers said. "In the context of known benefit of this treatment in patients with heart failure and left ventricular systolic dysfunction, and with the suggestion of a differential effect of sacubitril-valsartan in our trial in relation to left ventricular ejection fraction, future research should focus on the potential role of angiotensin receptor-neprilysin inhibition in patients with heart failure and ejection fraction that is below normal but not frankly reduced."
Keywords: ESC 19, ESC Congress, Angiotensins, Stroke Volume, Heart Failure
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