Spironolactone for heart failure with preserved ejection fraction
- PMID:24716680
- DOI: 10.1056/NEJMoa1313731
Spironolactone for heart failure with preserved ejection fraction
Abstract
Background: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction.
Methods: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.
Results: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis.
Conclusions: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number,NCT00094302.).
Comment in
- Lessons from the TOPCAT trial.McMurray JJ, O'Connor C.McMurray JJ, et al.N Engl J Med. 2014 Apr 10;370(15):1453-4. doi: 10.1056/NEJMe1401231.N Engl J Med. 2014.PMID:24716685No abstract available.
- Spironolactone for heart failure with preserved ejection fraction.Pfeffer MA, Pitt B, McKinlay SM.Pfeffer MA, et al.N Engl J Med. 2014 Jul 10;371(2):181-2. doi: 10.1056/NEJMc1405715.N Engl J Med. 2014.PMID:25006726No abstract available.
- Spironolactone for heart failure with preserved ejection fraction.Dalzell JR.Dalzell JR.N Engl J Med. 2014 Jul 10;371(2):179. doi: 10.1056/NEJMc1405715.N Engl J Med. 2014.PMID:25006727No abstract available.
- Spironolactone for heart failure with preserved ejection fraction.Efthimiadis GK, Zegkos T, Karvounis H.Efthimiadis GK, et al.N Engl J Med. 2014 Jul 10;371(2):179-80. doi: 10.1056/NEJMc1405715.N Engl J Med. 2014.PMID:25006728No abstract available.
- Spironolactone for heart failure with preserved ejection fraction.Kumar N, Garg N.Kumar N, et al.N Engl J Med. 2014 Jul 10;371(2):180. doi: 10.1056/NEJMc1405715.N Engl J Med. 2014.PMID:25006729No abstract available.
- Spironolactone for heart failure with preserved ejection fraction.Morawietz H, Bornstein SR.Morawietz H, et al.N Engl J Med. 2014 Jul 10;371(2):181. doi: 10.1056/NEJMc1405715.N Engl J Med. 2014.PMID:25006730No abstract available.
- Spironolactone did not reduce cardiac outcomes in symptomatic heart failure with preserved ejection fraction.Kelly J, Granger CB.Kelly J, et al.Ann Intern Med. 2014 Oct 21;161(8):JC6. doi: 10.7326/0003-4819-161-8-201410210-02006.Ann Intern Med. 2014.PMID:25329223No abstract available.
- Haben die Russen Studien getürkt?Holzgreve H.Holzgreve H.MMW Fortschr Med. 2017 Jun;159(11):36. doi: 10.1007/s15006-017-9783-2.MMW Fortschr Med. 2017.PMID:28608076German.No abstract available.
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