In HF hospitalization, benefits of sacubitril/valsartan largest in LVEF below normal
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Key takeaways:
- Sacubitril/valsartan showed benefit across the spectrum of left ventricular ejection fraction in stable patients with acute decompensated heart failure.
- Effects were strongest in those with EF 60% or less.
Sacubitril/valsartan was associated with reduced natriuretic peptides and lower risk for CV death and HF hospitalization across the spectrum of ejection fraction, particularly in those with EF below 60%, a speaker reported.
The prespecified pooled analysis of both the PIONEER-HF and PARAGLIDE-HF trials of sacubitril/valsartan (Entresto, Novartis) was presented at the Heart Failure Society of America Annual Scientific Meeting.
“Based on PARADIGM and PARAGON-HF, sacubitril/valsartan is indicated in the U.S. for patients with chronic heart failure, with benefits most clearly seen in those patients with EF below normal. PIONEER-HF and PARAGLIDE-HF investigated sacubitril/valsartan vs. an active control following stabilization for acute heart failure in patients with ejection fraction of 40% or less and greater than 40%, respectively,” Robert J. Mentz, MD, associate professor of medicine and population health science at Duke University School of Medicine and chief of the heart failure section at Duke University Medical Center, said during a presentation. “A prespecified pooled analysis of these latter two trials was designed to better estimate the safety and efficacy of sacubitril/valsartan when initiated in the hospital or soon after a worsening heart failure event, across the ejection fraction spectrum.”
The PIONEER-HF trial included 881 hemodynamically stabilized patients with acute decompensated HF with reduced EF who were randomly assigned to sacubitril 97 mg/valsartan 103 mg twice daily (median age, 61 years; 27% women) or enalapril 10 mg twice daily (median age, 63 years; 30% women). The primary endpoint was proportional change in N-terminal pro-B-type natriuretic peptide from baseline to weeks 4 and 8.
As Healio previously reported, sacubitril/valsartan was associated with greater reduction in peptides compared with enalapril and was also for a secondary serious composite clinical endpoint of death, HF rehospitalization, left ventricular assist device implant or transplant listing at 8 weeks.
PARAGLIDE-HF was a similarly designed trial in which researchers compared the effects of sacubitril/valsartan with valsartan alone in a cohort of 466 patients with HF with EF greater than 40%, worsening HF and NT-proBNP of 500 pg/mL or more. The median follow-up was 6 months.
For the present analysis, data from the sacubitril/valsartan (mean age, 65 years; 35% women; 31% Black) and control arms (mean age, 67 years; 38% women; 31% Black) of both studies were pooled to evaluated the efficacy and safety of the drug across the spectrum of EF.
The primary endpoint was the time-averaged change in NT-proBNP from baseline through weeks 4 and 8.
Mentz and colleagues reported an approximately 24% greater reduction in NT-proBNP from baseline in the sacubitril/valsartan arm (95% CI, 17-31; P < .0001), starting as early as week 1, compared with controls (ratio of change, 0.76; 95% CI, 0.69-0.83) and a 30% reduction in CV death or HF hospitalization out to 80 weeks (HR = 0.7; 95% CI, 0.54-0.91; P = .0077).
These findings correlated to one event prevented for every four patients treated per year, according to the presentation.
The researchers noted that the benefits of sacubitril/valsartan on CV death and HF hospitalization were consistent across the range of LVEF 60% or less (HR = 0.59; 95% CI, 0.44-0.79; P for interaction = .5); however, significant heterogeneity was observed for patients in the EF range greater than 60% (HR = 1.53; 95% CI, 0.8-2.91; P for interaction = .008).
CV death, HF hospitalizations and urgent HF visits were all lower in the sacubitril/valsartan group than in the control group, Mentz said.
The incidence of safety endpoints such as worsening renal function and all-cause mortality were numerically lower in the sacubitril/valsartan group compared with controls, but the difference was not significant. Incidence of hyperkalemia was numerically higher in the sacubitril/valsartan groups, but the difference was also not significant.
The researchers did observe an increased risk for symptomatic hypotension in the sacubitril/valsartan group compared with controls (18.3% vs. 13.7%; RR = 1.35; 95% CI, 1.05-1.72).
“With regard to application, this prespecified pooled analysis reinforces the overall benefits and safety and tolerability of sacubitril/valsartan in patients with worsening heart failure across the spectrum of ejection fraction, particularly that group with 60% or less, or below normal,” Mentz said during the presentation. “These data support present professional society guideline recommendations to begin sacubitril/valsartan, including as de novo treatment in hospitalized patients with acute heart failure, now extending insights across the ejection fraction spectrum.”
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Mentz RJ, et al. Late breaking clinical trials. Presented at: The Heart Failure Society of America Annual Scientific Meeting; Oct. 6-9, 2023; Cleveland.
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