Effectiveness and safety of mineralocorticoid receptor antagonists in heart failure patients with and without diabetes: a systematic review and meta-analysis

Abstract

Abstract Background Mineralocorticoid receptor antagonists (MRAs) have been shown to improve outcomes in various populations of heart failure (HF) patients. However, the impact of concomitant diseases, such as diabetes mellitus (DM), on these outcomes remains unclear. This meta-analysis aimed to evaluate the efficacy and safety of MRAs in heart failure patients with and without diabetes mellitus. Methods A systematic search was conducted on PubMed, Scopus, and Google Scholar databases up to April 30, 2024. Data analysis was performed using a random-effects model to account for variability across studies, and statistical analysis was carried out using Review Manager 5.4. Efficacy and safety parameters were evaluated in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Results The meta-analysis included a total of 21,832 subjects from ten studies. The pooled results demonstrated that MRAs, compared to placebo, significantly reduced all-cause mortality in HF patients with and without DM (RR: 0.85; 95%CI 0.75–0.96; p = 0.009). A similar effect was observed in HF patients without DM (RR: 0.83; 95%CI 0.71–0.97; p = 0.02), while no significant effect was detected in the DM subgroup (RR: 0.87; 95%CI 0.69–1.11; p = 0.27). Both treatments had comparable effects on cardiovascular mortality in HF patients with and without DM (RR: 0.88; 95%CI 0.82–0.94; p = 0.0002), in HF patients with DM (RR: 0.90; 95%CI 0.81–1.01; p = 0.08), and in the non-DM subgroup (RR: 0.86; 95%CI 0.79–0.94; p = 0.0009). MRAs significantly reduced the risk of cardiovascular mortality in HF patients with and without DM (RR: 0.82; 95%CI 0.72–0.94; p = 0.005) and in HF patients with DM (RR: 0.79; 95%CI 0.63–0.98; p = 0.03), but no significant effect was observed in the non-DM subgroup (RR: 0.85; 95%CI 0.69–1.05; p = 0.13). Furthermore, compared to placebo, MRAs were associated with an increased risk of hyperkalemia (> 5.5 mEq/L) in HF patients with and without DM (RR: 1.63; 95%CI 1.18–2.24; p = 0.003), particularly in HF patients with DM (RR: 1.44; 95%CI 0.97–2.13; p = 0.07) and in the non-DM subgroup (RR: 1.87; 95%CI 1.34–2.61; p = 0.0002). Conclusion MRAs are effective in reducing all-cause mortality, cardiovascular death, and cardiovascular mortality in heart failure patients. However, the use of MRAs is associated with an increased risk of hyperkalemia, necessitating careful monitoring, particularly in patients with diabetes mellitus.

Keywords

• Heart failure
• Diabetes mellitus
• Mineralocorticoid receptor antagonists
• Steroid