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Sacubitril/Valsartan for Worsening Heart Failure
Quick Takes
- Sacubitril/valsartan reduced CV death or HF hospitalization compared with enalapril or valsartan among patients with a recent worsening HF event.
- These data highlight a potential opportunity to optimize medical therapy in the high-risk population early after a recent worsening HF event across the spectrum of EF.
- Additional prospective studies are indicated to validate these results and elucidate the mechanisms responsible for heterogeneity in the effect of ARNI in patients with HF and EF ≤60%.
Study Questions:
What is the safety and efficacy of sacubitril/valsartan when initiated during hospitalization or soon after a worsening heart failure (WHF) event and among patients with HF across the spectrum of ejection fraction (EF)?
Methods:
The investigators conducted a pooled analysis of PIONEER-HF and PARAGLIDE-HF trials. PIONEER-HF and PARAGLIDE-HF were double-blind, randomized trials of sacubitril/valsartan versus control therapy (enalapril or valsartan, respectively). All participants in PIONEER-HF and 69.5% in PARAGLIDE-HF were enrolled during hospitalization for HF after stabilization. The remainder in PARAGLIDE-HF were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through end of follow-up, adjusting for trial.
Results:
The pooled analysis included 1,347 patients (881 PIONEER-HF, 466 PARAGLIDE-HF). Baseline characteristics included: median age 66 years, 36% women, 31% Black, 34% de novo HF, median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan versus control (n = 1,130; ratio of change, 0.76; 95% confidence interval [CI], 0.69-0.83; p < 0.0001). Cardiovascular (CV) death or hospitalization for HF was reduced by 30% with sacubitril/valsartan versus control (hazard ratio, 0.70; 95% CI, 0.54-0.91; p = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio, 1.35; 95% CI, 1.05-1.72).
Conclusions:
The authors report that in patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%.
Perspective:
This participant-level pooled analysis of the PIONEER-HF and PARAGLIDE-HF randomized trials reports that sacubitril/valsartan reduced CV death or hospitalization for HF compared with enalapril or valsartan among patients with a recent WHF event. These data highlight a potential opportunity to optimize medical therapy in the high-risk population early after a recent WHF event across the spectrum of EF. Of note, although prespecified, the subgroup analyses and testing for heterogeneity should be considered exploratory and additional prospective studies are indicated to validate these results and elucidate the mechanisms for heterogeneity in the effect of angiotensin receptor/neprilysin inhibitor (ARNI) in patients with HF and EF ≤60%.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Heart Failure, Stroke Volume, Valsartan
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