Effects of Sacubitril/Valsartan vs Valsartan in De Novo vs Acute on Chronic HFpEF and HFmrEF

Background: Decompensated heart failure (HF) can be categorized as de novo or worsening of chronic HF. In PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF), among patients with an ejection fraction >40% that stabilized after worsening HF, sacubitril/valsartan led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and was associated with clinical benefit compared to valsartan.

Objectives: This prespecified analysis characterized patients with de novo vs worsening chronic HF in PARAGLIDE-HF and assessed the interaction between HF chronicity and the effect of sacubitril/valsartan.

Methods: Patients were classified as de novo (first diagnosis of HF) or chronic (known HF prior to the index event). Time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8 was analyzed using an analysis of covariance model. A win ratio consisting of time to cardiovascular death, number and times of HF hospitalizations during follow-up, number and times of urgent HF visits during follow-up, and time-averaged proportional change in NT-proBNP was assessed for each group.

Results: Of the 466 participants, 153 (33%) had de novo HF and 313 (67%) had chronic HF. De novo patients had lower rates of atrial fibrillation/flutter and lower creatinine. There was a nonsignificant reduction in NT-proBNP with sacubitril/valsartan vs valsartan for de novo (0.82; 95% CI: 0.62-1.07) and chronic HF (0.88; 95% CI: 0.73-1.07), interaction P = 0.66. The win ratio was nominally in favor of sacubitril/valsartan for both de novo (1.12; 95% CI: 0.70-1.58) and chronic HF (1.24; 95% CI: 0.89-1.71).

Conclusions: There is no interaction between HF chronicity and the effect of sacubitril-valsartan.