Key result
Aldosterone receptor antagonists significantly reduced the odds of all-cause death (OR 0.79) and cardiovascular hospitalizations in patients with chronic heart failure, with benefits limited to those with reduced ejection fraction.
Why the study?
Does the addition of aldosterone receptor antagonists to conventional therapy reduce all-cause death and cardiovascular hospitalizations in patients with chronic heart failure?
Meta-Analysis (n=15,671)
Does the addition of aldosterone receptor antagonists to conventional therapy reduce all-cause death and cardiovascular hospitalizations in patients with chronic heart failure?
Effect estimate: OR 0.79 (95% CI 0.73 - 0.87)
Aldosterone receptor antagonists significantly reduce all-cause mortality and cardiovascular hospitalizations in patients with HFrEF, but not HFpEF, while increasing the risk of hyperkalemia.
Supports addition of aldosterone receptor antagonists in HFrEF; reinforces prior trial evidence for mortality and hospitalization reduction.
BACKGROUND: Aldosterone receptor antagonists (ARAs) have been associated with improved clinical outcomes in patients with heart failure with reduced left ventricular ejection fraction (HFREF), but not in those with heart failure with preserved left ventricular ejection fraction (HFpEF). With the aim to study this topic more deeply, we carried out a meta-analysis of selective and non-selective ARAs in HFREF and HFpEF. METHODS: We searched PubMed and Scopus databases. We decided to incorporate in the meta-analysis only randomized controlled trials (RCTs) of ARAs in patients with chronic heart failure (CHF) if they met the following criteria: experimental groups included patients with CHF treated with ARAs in addition to the conventional therapy; control groups included patients with CHF receiving conventional therapy without ARAs. Outcomes of interest were all-cause death, hospitalizations from cardiovascular cause, hyperkalemia, or gynecomastia. RESULTS: We detected 15 studies representing 15,671 patients. ARAs were associated with a reduced odds of all-cause death (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.73 - 0.87) and hospitalizations from cardiovascular cause (OR: 0.73; 95% CI: 0.61 - 0.89). However, subgroup analysis showed that these advantages were limited to HFREF (all-cause death: OR: 0.77, 95% CI: 0.69 - 0.84; hospitalizations from cardiovascular cause: OR: 0.66, 95% CI: 0.51 - 0.85), but they did not affect the HFpEF group (all-cause death: OR: 0.91, 95% CI: 0.76 - 1.1; hospitalizations from cardiovascular cause: OR: 0.85, 95% CI: 0.7 - 1.09). ARAs increased the risk of hyperkalemia (OR: 2.17; 95% CI: 1.88 - 2.5). Non-selective ARAs, but not selective ARAs, increased the risk of gynecomastia (OR: 8.22, 95% CI: 4.9 - 13.81 vs. OR: 0.74, 95% CI: 0.43 - 1.27). CONCLUSIONS: ARAs reduced the risk of adverse cardiac events in HFREF but not HFpEF. In particular, ARA use in HFpEF patients is questionable, since in this CHF type, no significant improvement in all-cause death and cardiovascular hospitalizations was demonstrated with ARA treatment, in the face of the well-known risks of hyperkalemia and/or gynecomastia that chronic ARA therapy entails. Selective ARAs were equally effective as non-selective ARAs, without the risk of gynecomastia.
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Vecchis et al. (2016) conducted a meta-analysis in Chronic heart failure (n=15,671). Aldosterone receptor antagonists (ARAs) vs. Conventional therapy without ARAs was evaluated on All-cause death (OR 0.79, 95% CI 0.73 - 0.87). Aldosterone receptor antagonists significantly reduced the odds of all-cause death (OR 0.79) and cardiovascular hospitalizations in patients with chronic heart failure, with benefits limited to those with reduced ejection fraction.
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