Relative Efficacy of Spironolactone, Eplerenone, and cAnRenone in patients with Chronic Heart failure (RESEARCH): a systematic review and network meta-analysis of randomized controlled trials.
Lutz FrankensteinSvenja SeideTobias TägerKatrin JensenHanna FröhlichAndrew L ClarkMirjam SeizHugo A KatusPaul NeeLorenz UhlmannHuseyin NaciDan AtarPublished in: Heart failure reviews (2021)
This study aims to assess the comparative benefit and risk profile of treatment with mineralocorticoid receptor antagonists (MRAs) with regard to all-cause mortality (primary endpoint), cardiovascular mortality, or heart failure (HF)-related hospitalization (secondary endpoints) and the safety endpoints hyperkalemia, acute renal failure, and gynecomastia in patients with chronic HF. We conducted a systematic review and network meta-analysis following PRISMA-P and PRISMA-NMA guidelines. From 16 different sources, 14 randomized controlled trials totaling 12,213 patients testing an active treatment of either spironolactone, eplerenone, or canrenone/potassium-canreonate in adults with symptomatic HF due to systolic dysfunction reporting any of the above endpoints were retained. Efficacy in comparison to placebo/standard medical care with respect to all-cause mortality was confirmed for spironolactone and eplerenone while no conclusion could be drawn for canrenone (HR 0.69 (0.62; 0.77), 0.82 (0.75; 0.91), and 0.50 (0.17; 1.45), respectively). Indirect comparisons hint a potential (non-significant) preference of spironolactone over eplerenone (HR 0.84 (0.68; 1.03)). The overall risk of bias was low to intermediate. Results for secondary endpoints as well as sensitivity analyses essentially mirrored these findings. The beta-blocker adjusted meta-analysis for the primary endpoint showed the same tendency as the unadjusted one (HR 0.39 (0.07; 2.03)). Results need to be interpreted with caution, though, as the resultant mix of patient- and study-level covariates produced unstable statistical modeling. We found no significant and systematic superiority of either MRA regarding efficacy toward all endpoints considered in both direct and indirect comparisons.
Keyphrases
- heart failure
- systematic review
- meta analyses
- ejection fraction
- acute heart failure
- left ventricular
- blood pressure
- newly diagnosed
- end stage renal disease
- oxidative stress
- liver failure
- clinical trial
- emergency department
- prognostic factors
- atrial fibrillation
- risk assessment
- coronary artery disease
- drinking water
- computed tomography
- magnetic resonance imaging
- intensive care unit
- angiotensin ii
- peritoneal dialysis
- replacement therapy
- patient reported
- patient reported outcomes
- double blind
- case control