The study shows a potential benefit of sacubitril/valsartan in patients with heart failure with an excretion rate greater than 40%.

Sacubitril/valsartan leads to a greater decrease in plasma NT-proBNP levels than valsartan alone after stabilization for exacerbation of heart failure in patients with an ejection fraction (EF) greater than 40%.according The latest science was presented today at Heart Failure 2023, a scientific conference of the European Society of Cardiology (ESC), and published in Journal of the American College of Cardiology.

These data add to the evidence supporting the potential treatment benefit of sacapitril/valsartan in patients with an EF greater than 40% and especially in those with an EF below normal (<60%). The findings may influence future guidance for the use of the drug in this population, both in and out of hospital and for those with acute, chronic or de novo heart failure."

Dr. Robert Mintz, principal investigator, Duke University Medical Center, Durham, US

Study guidelines recommend sacubitril/valsartan to reduce hospital admissions in patients with heart failure with preserved EF (HFpEF; EF >50%) and/or slightly reduced EF (HFmrEF; EF 41-49%). Recommendations vary around the world, with some benefits noted being most noticeable in those with EF on the lower end of this spectrum (ie, below normal).

The PARAGON-HF trial excluded patients with decompensated heart failure, but post hoc analysis suggested greater benefit with sacubitril/valsartan in those recently hospitalized. It was not known whether initiation of sacubitril/valsartan was safe and effective in patients with an EF greater than 40% after deterioration in heart failure. In addition, more data were required in populations excluded by PARAGON-HF (estimated glomerular filtration rate). [eGFR] <30 mL/min/1.73m²A systolic blood pressure less than 110 mm Hg and a body mass index [BMI] > 40 kg/m²).

PARAGLIDE-HF evaluated the effect of sacubitril/valsartan versus valsartan on changes in NT-proBNP, safety and tolerability in heart failure patients with EF above 40% who were stabilized after deterioration of heart failure. The primary endpoint was the mean time relative change in NT-proBNP from baseline through weeks 4 and 8. It was chosen to reflect the PIONEER-HF trial, which found that among patients with heart failure with a lower EF (less than (40%) admitted to hospital with acute decompensated heart failure, sacubitril/valsartan led to a greater decrease in NT-proBNP concentration than enalapril.

Patients were recruited from 100 sites in the United States and Canada. A total of 466 patients were enrolled with an EF above 40% within 30 days of exacerbation of heart failure (69% were enrolled while in hospital). The median age was 70 years, 52% were women and 22% were black. Participants were randomly allocated at a 1:1 ratio to either sacubitril/valsartan or valsartan. The decrease in mean time in NT-proBNP was greater with sacubitril/valsartan than with valsartan (ratio of change 0.85; 95% confidence interval [CI] 0.73 – 0.999; p = 0.049).

The secondary composite hierarchical score consisted of a) time to cardiovascular death, b) number and timing of hospitalizations for heart failure, c) number and timing of urgent heart failure visits and d) mean relative change in NT-proBNP from baseline to weeks 4–8. Evaluate this outcome using win-ratio analysis, which takes into account the clinical hierarchy and timing of each endpoint component. The most critical events are given higher priority and analyzed first. The hierarchical outcome favored sacubitril/valsartan (as did both components) but was not significant (unmatched win ratio 1.19; 95% confidence interval 0.93–1.52; p = 0.16).

With respect to other secondary endpoints, compared with valsartan, sacubitril/valsartan reduced the worsening of renal function (odds ratio [OR] 0.61; 95% CI 0.40–0.93). There was more symptomatic hypotension in the sacubitril/valsartan group (odds ratio 1.73; 95% confidence interval 1.09–2.76). Importantly, subgroup analyzes showed evidence of a greater treatment effect in those with a 60% EF of change in NT-proBNP (0.78; 95% CI 0.61–0.98) and the hierarchical score (win ratio 1.46; 95% CI, 1.09–1.95). ).

Dr Mintz said: “PARAGLIDE-HF supplemented PARAGON-HF by concentrating on patients who had stabilized after a state of worsening heart failure with an EF higher than 40% similar to how PIONEER-HF supplemented PARADIGM-HF in patients with a lower EF. HF had no run-in period, which allowed both newly diagnosed heart failure and improved EF, including those with severe heart failure without specific requirements for echocardiography and generally had a diverse study population (52% women, 22 % of black individuals).The trial also allowed patients with a glomerular filtration rate of up to 20 mL/min/1.73m²and systolic blood pressure of 100 mmHg and any BMI. The wide and diverse population included in PARAGLIDE-HF supports the generalizability of these data to similar patients in routine practice.”