Greater reduction in NT-proBNP with ARNI compared to ARB in HFmrEF/HFpEF after worsening HF event

PARAGLIDEHF: Sacubitril/Valsartan versus valsartan on changes in NTproBNP, safety, and tolerability in patients with EF>40% stabilized after a WHF Event

Presented at ESC Heart Failure 2023 by: Robert Mentz, MD - Durham, NC, USA

Introduction and methods

Background

Sacubitril/valsartan is recommended by several society guidelines to reduce hospitalizations in HFmrEF and HFpEF. A post-hoc analysis of the PARAGON-HF trial suggested that sacubitril/valsartan has greater benefits in patients who were recently hospitalized. However, It remained unclear whether initiation of sacubitril/valsartan is safe and effective in patients with HF and EF >40% stabilized after a worsening HF (WHF) event.

Aim of the study

The authors compared the effects of sacubitril/valsartan with valsartan in patients with HFmrEF or HFpEF who had experienced a recent WHF event.

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Methods

In the PARAGLIDE-HF trial patients (n=466) with HFmrEF and HFpEF with a recent WHF event were included. A recent WHF was defined as hospitalization, a urgent HF visit or a ER visit within 30 days of randomization. Patients were eligible if they had: SBP ≥100 mmHg; NT-proBNP ≥500 pg/mL; GFR ≥20 ml/min/1.73m²; and K ≤5.2 mEq/L. Patients were randomized to 96 mg/103 mg sacubitril/valsartan twice daily or 160 mg valsartan twice daily (n=233 in each group).

Outcomes

The primary endpoint was the proportional change in NT-proBNP from baseline to weeks 4 and 8.

Main results

Primary endpoint

• A greater reduction in NT-proBNP was detected in the sacubitril/valsartan group compared to the valsartan group (difference of 15%; 95%CI: 0-27%; P=0.049).

Secondary endpoints

• The win ratio in the hierarchical CV composite (which included time to CV death, HF hospitalization, urgent HF visits, and change in NT-proBNP) tended to be in favor of sacubitril/valsartan compared to valsartan (unmatched win ratio: 1.19; 95%CI: 0.93-1.52; P=0.16). This trend was also present in each of the individual components of the composite.
• The incidences of recurrent CV composite (which included CV death, HF hospitalizations and urgent HF visits) and worsening renal function composite (which included renal death, ESRD, and ≥50% decline in eGFR) tended to be lower in the sacubitril/valsartan group compared to the valsartan group (rate ratio: 0.83; 95%CI: 0.57-1.23; and rate ratio: 0.62; 95%CI: 0.25-1.56, respectively).
• Safety results showed that symptomatic hypotension occurred more often in the sacubitril/valsartan group compared to the valsartan group (OR: 1.73; 95%CI: 1.09-2.76). Worsening renal function occurred less often in the sacubitril/valsartan group compared to the valsartan group (OR: 0.61; 95%CI: 0.40-0.93).

Subgroup analysis

• In a pre-specified subgroup analysis with patients with LVEF ≤60%, a greater reduction in NT-proBNP was observed in the sacubitril/valsartan group vs. the valsartan group in patients with EF >40% to ≤60%, but not in patients with EF >60% (P for interaction=0.033).

Conclusion

In patients with EF>40% who were stabilized after recent WHF, treatment with sacubitril/valsartan led to greater reductions in NT-proBNP compared to treatment with valsartan. The win ratio in the hierarchical CV composite outcome tended to be in favor of sacubitril/valsartan compared to valsartan. In addition, sacubitril/valsartan was associated with a lower rate of worsening renal function, but with a higher rate of symptomatic hypertension.

-Our reporting is based on the information provided at ESC Heart Failure 2023 –

The findings of this study were simultaneously published in J Am Coll Cardiol. 2023