MRA use not associated with worse kidney outcomes in HFrEF
Safety of continuing mineralocorticoid receptor antagonist treatment in patients with heart failure with reduced ejection fraction and severe kidney disease: data from Swedish Heart Failure RegistryLiterature - Guidetti F, Lund LH, Benson L, et al. - Eur J Heart Fail. 2023 Oct 5 [Online ahead of print]. doi: 10.1002/ejhf.3049
Introduction and methods
MRAs are frequently underprescribed or discontinued in patients with HFrEF —especially in those with CKD —despite the strong level of evidence supporting their efficacy and safety, irrespective of baseline renal function [3-7].
Aim of the study
The authors evaluated the risk of renal outcomes, all-cause mortality, and all-cause hospitalization associated with MRA use across the eGFR spectrum in a large, real-world HFrEF cohort, including patients with severe CKD (i.e., eGFR <30 mL/min per 1.73 m²).
For this observational cohort study, data of 33,942 patients with HFrEF (EF <40%) who were enrolled in the Swedish Heart Failure Registry between 2012 and 2020 were collected. Dialysis at the index visit was an exclusion criterion. At the index date, MRA use and patients’ renal function were assessed.
The primary endpoint was a composite renal outcome of dialysis initiation, renal death, renal failure hospitalization, or hyperkalemia hospitalization after 1 year. Additional endpoints were all-cause mortality and all-cause hospitalization, both assessed at 1 year.
- At the index date, 17,489 patients (51%) were prescribed an MRA. Use of MRA decreased with worsening renal function, ranging from 54% for patients with eGFR ≥60 mL/min per 1.73 m² (n=20,868) to 32% for those with eGFR <30 mL/min per 1.73 m² (n=1834). During follow-up , MRA discontinuation was observed in 11% of the patients, evenly distributed across the eGFR spectrum.
- Of 38 patient characteristics, eGFR ≥60 mL/min per 1.73 m² was the strongest independent predictor of MRA use at baseline (OR for eGFR ≥60 vs.<30 mL/min per 1.73 m²: 2.85; 95%CI: 2.49–3.26). Other relevant predictors were potassium >5 mmol/L (compared with <3.5 mmol/L), more severe HF (i.e., higher NYHA class, use of HF devices or diuretics), beta-blocker use, history of hypertension, and liver disease.
- In multivariable Cox regression analyses, the incidence rate of the composite renal outcome at 1 year was 14.6 per 1000 patient-years among MRA users compared with 17.5 per 1000 patient-years for nonusers (unadjusted HR: 0.83; 95%CI: 0.79–0.88). After adjustment for baseline patient characteristics such as age, sex, and NYHA class, the HR was 1.04 (95%CI: 0.98–1.10), which was consistent across the eGFR spectrum (P for interaction=0.29). In patients with eGFR <30 mL/min per 1.73 m², the adjusted HR was 1.01 (95%CI: 0.87–1.17).
- The 1-year rate of all-cause mortality was 12.9 per 1000 patient-years for MRA users versus 15.9 per 1000 patient-years for nonusers (adjusted HR: 1.02; 95%CI: 0.97–1.08; P for interaction by eGFR class=0.39). The adjusted HR was 1.07 (95%CI: 0.92–1.25) for patients with eGFR <30 mL/min per 1.73 m².
- The 1-year all-cause hospitalization rate was 55.6 per 1000 patient-years for MRA users versus 60.5 per 1000 patient-years for nonusers (adjusted HR: 0.99; 95%CI: 0.95–1.02; P for interaction by eGFR class=0.46). In patients with eGFR <30 mL/min per 1.73 m², the adjusted HR was 1.03 (95%CI: 0.91–1.17).
In a real-world Swedish cohort study, 51% of the HFrEF patients were prescribed an MRA and MRA use decreased with worsening renal function. However, MRA use was not associated with a higher risk of the composite renal outcome, all-cause mortality, and all-cause hospitalization at 1 year. The safety profile of MRAs was consistent across the eGFR spectrum and, notably, also in patients with severe CKD. The authors believe their “findings might suggest not to encourage MRA discontinuation in patients with severe CKD if strict laboratory surveillance is feasible.”