Abstract
BackgroundMineralocorticoid receptor antagonists (MRAs) have been associated with improved patient outcomes in patients with heart failure with reduced ejection fraction (HFrEF) but not preserved ejection fraction (HFpEF). We conducted a systematic review and meta-analysis of selective and nonselective MRAs in HFrEF and HFpEF.MethodsWe searched Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. We included randomized controlled trials (RCT) of MRAs in adults with HFpEF or HFrEF if they reported data on major adverse cardiac events or drug safety.ResultsWe identified 15 studies representing 16321 patients. MRAs were associated with a reduced risk of cardiovascular death (RR 0.81 [0.75–0.87], I2 0%), all-cause mortality (RR 0.83 [0.77–0.88], I2 0%), and cardiac hospitalizations (RR 0.80 [0.70–0.92], I2 58.4%). However, an a-priori specified subgroup analysis demonstrated that these benefits were limited to HFrEF (cardiovascular death RR 0.79 [0.73–0.86], I2 0%; all-cause mortality RR 0.81 [0.75–0.87], I2 0%; cardiac hospitalizations RR 0.76 [0.64–0.90], I2 68%), but not HFpEF (all-cause mortality RR 0.92 [0.79–1.08], I2 0%; cardiac hospitalizations RR 0.91 [0.67–1.24], I2 17%). MRAs increased the risk of hyperkalemia (RR 2.03 [1.78–2.31], I2 0%). Nonselective MRAs, but not selective MRAs increased the risk of gynecomastia (RR 7.37 [4.42–12.30], I2 0% vs. RR 0.74 [0.43–1.27], I2 0%). Evidence was of moderate quality for cardiovascular death, all-cause mortality and cardiovascular hospitalizations; and high-quality for hyperkalemia and gynecomastia.ConclusionsMRAs reduce the risk of adverse cardiac events in HFrEF but not HFpEF. MRA use in HFpEF increases the risk of harm from hyperkalemia and gynecomastia. Selective MRAs are equally effective as nonselective MRAs, without a risk of gynecomastia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0425-x) contains supplementary material, which is available to authorized users.
Highlights
Mineralocorticoid receptor antagonists (MRAs) have been associated with improved patient outcomes in patients with heart failure with reduced ejection fraction (HFrEF) but not preserved ejection fraction (HFpEF)
We demonstrate that treatment of HF with preserved ejection fraction (HFpEF) with MRAs does not reduce adverse cardiac events
We suggest continued usage of MRAs in HFrEF, where there is a significant reduction in adverse cardiac outcomes, e.g., cardiovascular death (NNT 34 [26–50]), or allcause mortality (NNT 32 [24–45])
Summary
Mineralocorticoid receptor antagonists (MRAs) have been associated with improved patient outcomes in patients with heart failure with reduced ejection fraction (HFrEF) but not preserved ejection fraction (HFpEF). We conducted a systematic review and meta-analysis of selective and nonselective MRAs in HFrEF and HFpEF. Heart failure (HF) has significant morbidity and is often a result of impaired left ventricular myocardial function [1]. HF with preserved ejection fraction (HFpEF) involves impaired myocardial function with normal left ventricle size and ejection fraction; in contrast, HF with reduced ejection fraction (HFrEF) involves an enlarged left ventricle size and reduced ejection fraction. MRAs can be selective (e.g., eplerenone) or nonselective (e.g., spironolactone). Eplerenone was synthesized through chemical modification of spironolactone in order to enhance binding of mineralocorticoid receptors while reducing off-target binding to progesterone or androgen receptors [10]. Eplerenone is associated with lower rates of impotence, gynecomastia or breast pain in comparison to spironolactone [11, 12]
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