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Association of Spironolactone Use With All-Cause Mortality in Heart Failure A Propensity Scored Cohort Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
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2013 (English)In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 6, no 2, 174-183 p.Article in journal (Refereed) Published
Abstract [en]

Background-In 3 randomized controlled trials in heart failure (HF), mineralocorticoid receptor antagonists reduced mortality. The net benefit from randomized controlled trials may not be generalizable, and eplerenone was, but spironolactone was not, studied in mild HF. We tested the hypothesis that spironolactone is associated with reduced mortality also in a broad unselected contemporary population with HF and reduced ejection fraction, in particular New York Heart Association (NYHA) I-II. Methods and Results-We prospectively studied 18 852 patients (age 71+/-12 years; 28% women) with NYHA I-IV and ejection fraction <40% who were registered in the Swedish Heart Failure Registry between 2000 and 2012 and who were (n=6551) or were not (n=12 301) treated with spironolactone. We derived propensity scores for spironolactone treatment based on 41 covariates. We assessed survival by Cox regression with adjustment for propensity scores and with matching based on propensity score. We performed sensitivity and residual confounding analyses and analyzed the NYHA I-II and III-IV subgroups separately. One-year survival was 83% versus 84% in treated versus untreated patients (log rank P<0.001). After adjustment for propensity scores, the hazard ratio for spironolactone was 1.05 (95% confidence interval, 1.00-1.11; P=0.054). Spironolactone interacted with NYHA (P<0.001). In the NYHA I-II subgroup, after adjustment for propensity scores, the hazard ratio for spironolactone was 1.11 (95% confidence interval, 1.02-1.21; P=0.019). Conclusions-In an unselected contemporary population of HF with reduced ejection fraction, spironolactone was not associated with reduced mortality. The net benefits of spironolactone may be lower outside the clinical trial setting and in milder HF.

Place, publisher, year, edition, pages
2013. Vol. 6, no 2, 174-183 p.
Keyword [en]
aldosterone, epidemiology, heart failure, mineralocorticoids, outcomes research, pharmacoepidemiology
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-247731DOI: 10.1161/CIRCHEARTFAILURE.112.000115ISI: 000331381200010PubMedID: 23386667OAI: oai:DiVA.org:uu-247731DiVA: diva2:797236
Available from: 2015-03-23 Created: 2015-03-23 Last updated: 2017-12-04Bibliographically approved

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Svennblad, BodilMelhus, HåkanHallberg, Pär

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