Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial

Eur J Heart Fail. 2021 Aug;23(8):1313-1321. doi: 10.1002/ejhf.2221. Epub 2021 Jun 3.

Abstract

Aims: Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m2 . We evaluated the relationship between the efficacy of vericiguat and baseline and subsequent changes in renal function.

Methods and results: In VICTORIA, core laboratory serum creatinine was measured at baseline (n = 4956) and weeks 16, 32, and 48. Worsening renal function (WRF), defined as an increase ≥0.3 mg/dL in creatinine from baseline to week 16, was assessed via a Cox model with respect to subsequent primary events. Mean age was 69 years, 24% were female, and mean baseline eGFR was 61 mL/min/1.73 m2 . During 48 weeks of treatment, the trajectories in eGFR and creatinine with vericiguat were similar to placebo (P = 0.50 and 0.18). The beneficial effects of vericiguat on the primary outcome were not influenced by baseline eGFR (interaction P = 0.48). WRF occurred in 15% of patients and was associated with worse outcomes (adjusted hazard ratio 1.28, 95% confidence interval 1.11-1.47; P < 0.001), but the beneficial effects of vericiguat on the primary outcome were similar in patients with or without WRF (interaction P = 0.76).

Conclusion: Renal function trajectories were similar between vericiguat- and placebo-treated patients and the beneficial effects of vericiguat on the primary outcome were consistent across the full range of eGFR and irrespective of WRF.

Keywords: Estimated glomerular filtration rate; Heart failure; Heart failure with reduced ejection fraction; Renal function.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Glomerular Filtration Rate
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Heterocyclic Compounds, 2-Ring
  • Humans
  • Kidney / physiology
  • Male
  • Pyrimidines
  • Stroke Volume
  • Treatment Outcome

Substances

  • Heterocyclic Compounds, 2-Ring
  • Pyrimidines
  • vericiguat