Physicians' Academy for Cardiovascular Education

Limited influence of ARNI on loop diuretic use in symptomatic HFpEF

Sacubitril/valsartan and loop diuretic requirement in heart failure with preserved ejection fraction in the PARAGON-HF trial

Literature - Chatur S, Claggett BL, Vardeny O, et al. - Eur J Heart Fail. 2022 Oct 1. doi: 10.1002/ejhf.2703.

Introduction and methods

Background

In patients with HFrEF, treatment with sacubitril/valsartan resulted in a lower loop diuretic requirement, compared with enalapril [1]. Consequently, the ESC guidelines state that in patients with HFrEF, the use of sacubitril/valsartan may allow a reduction in loop diuretic requirement [2], but data in patients with HFpEF are lacking. Previously, the PARAGON-HF study showed that in patients with symptomatic HFpEF, treatment with sacubitril/valsartan leads to a non-statistically significant lower incidence of the primary composite outcome of CV death or total hospitalizations for HF, compared with valsartan [3]. However, it is unclear how treatment with sacubitril/valsartan affects longitudinal patterns in loop diuretic use and to what extent the efficacy and safety of sacubitril/valsartan is affected by background diuretic therapy in patients with symptomatic HFpEF.

Aim of the study

This post hoc analysis of data from the PARAGON-HF study examined the influence of treatment with sacubitril/valsartan on longitudinal patterns in loop diuretic use and the extent to which the efficacy and safety of sacubitril/valsartan is affected by background diuretic therapy in patients with symptomatic HFpEF.

Methods

The researchers conducted a post hoc analysis of data from the PARAGON-HF study. In this multicenter, double-blind phase 3 study, 4822 adults ≥50 years with symptomatic HFpEF were randomized to twice-daily sacubitril/ valsartan (97 mg sacubitril and 103 mg valsartan) or valsartan (target dose of 160 mg). Participants had a NYHA class II-IV, elevated natriuretic peptide levels and evidence of structural heart disease. In this post hoc analysis, 4796 patients for whom data were available on diuretic therapy at baseline were divided into 3 groups: patients on no diuretic (n=341), a non-loop diuretic (n=698), or a loop diuretic (n=3757). The dose of loop diuretics was converted to an equivalent dose for furosemide (FED) and categorized as <40 (n=1255), 40 (n=1589) or >40 mg (n=913). Patients treated with a mineralocorticoid receptor antagonist alone were considered as if they were on no diuretic. Patients on multiple diuretics (n=330) were assigned to a group based on the most potent diuretic (e.g., patients treated with a non-loop diuretic and a loop diuretic were assigned to the group of patients on a loop diuretic).

Outcomes

The primary outcome was a composite of CV death and total hospitalizations for HF. Safety outcomes included the occurrence of hypotension (SBD <100 mmHg), elevated serum creatinine levels (≥2.0, ≥2.5 and ≥3.0 mg/dL) and drug discontinuation. The researchers were also interested in changes in loop diuretic use over time.

Main results

Efficacy

.

Safety

Changes in loop diuretic use over time

Conclusion

This post hoc analysis of data from the PARAGON-HF study shows that in patients with symptomatic HFpEF, the influence of sacubitril/valsartan on longitudinal patterns in loop diuretic use is limited. Background diuretic therapy does not affect the efficacy and safety of sacubitril/valsartan, compared with valsartan.

In their summary, the investigator noted that “in contrast to HFreF, routine diuretic dose reduction on sacubitril/valsartan initiation in HFpEF may be less warranted”.

References

Show references

Find this article online at Eur J Heart Fail.

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