Meta-analysis shows beneficial effects of MRAs in all HF patients

This summary is based on the presentation of Pardeep Jhund, MD, PhD (Glasgow, UK) at the ESC Congress 2024 - MRAs in heart failure - An individual patient data meta-analysis of randomised trials.

Introduction and methods

Clinical guidelines strongly recommend MRA treatment in patients with HFrEF to reduce the risks of hospitalization and mortality. However, these drugs are often clinically underused for fear of hyperkalemia. In addition, their efficacy in HFmrEF and HFpEF is unclear.

To test the consistency of the effects of MRAs across several clinical outcomes and across the LVEF spectrum, the researchers performed a systematic review and prespecified individual patient-level meta-analysis of 4 placebo-controlled RCTs. The RALES (spironolactone) and EMPHASIS-HF trials (eplerenone) enrolled HFrEF patients, whereas the TOPCAT (spironolactone) and FINEARTS-HF (finerenone) trials included both HFmrEF and HFpEF patients. The total study population comprised 13,846 patients.

The primary endpoint was a composite outcome of time to first HF hospitalization or CV death. Secondary endpoints were the individual components of the primary endpoint, total (first and recurrent) HF hospitalizations, total HF hospitalizations and CV death, and all-cause mortality. Safety endpoints included serum creatinine and potassium levels, eGFR, and systolic blood pressure. To assess the heterogeneity of effect in the HF populations, the interaction between trials and treatment effect was also investigated.

Main results

• MRA treatment reduced the risk of HF hospitalization or CV death compared with placebo (HR: 0.77; 95%CI: 0.72–0.83).
• There was a significant interaction between trials and treatment (P for interaction=0.0012) due to the greater efficacy in the HFrEF trials (HR: 0.66; 95%CI: 0.59–0.73) compared with the HFmrEF/HFpEF trials (HR: 0.87; 95%CI: 0.79–0.95).
• The effect of MRA treatment was consistent across several key subgroups in the HFrEF and HFmrEF/HFpEF trials.
• The risk of hyperkalemia (potassium >5.5 mmol/L) was increased in patients treated with MRAs compared with those receiving placebo (13.5% vs. 6.4%; OR: 2.27; 95%CI: 2.02–2.56), but the frequency of serious hyperkaliemia (potassium >6.0 mmol/L) was low in both groups (2.9% vs. 1.4%).
• The incidence rate of hypokalemia (potassium <3.5 mmol/L) was lower in the MRA group than the placebo group (7.5% vs. 13.8%; OR: 0.51; 95%CI: 0.45–0.57).

Conclusion

This individual patient-level meta-analysis of 4 RCTs showed MRAs reduced the risk of the composite outcome of HF hospitalization or CV death compared with placebo in HF patients across the LVEF spectrum. Although MRA-treated patients had a higher risk of hyperkalemia than placebo-treated patients, the rate of serious hyperkaliemia was low. Moreover, the risk of hypokalemia was lower in the MRA group. Dr. Jhund therefore advised to use MRAs in HF patients who have no contraindication.

- Our reporting is based on the information provided at the ESC Congress 2024 -

The findings of this study were simultaneously published in The Lancet.