Are beta-blockers needed in patients receiving spironolactone for severe chronic heart failure? An analysis of the COPERNICUS study

Krum, H; Mohacsi, P; Katus, HA; Tendera, M; Rouleau, JL; Fowler, MB; Coats, AJ; Roecker, EB; Packer, M; Carvedilol, Prospective Randomized Cumulative Survival (COPERNICUS) Study Gr (2006). Are beta-blockers needed in patients receiving spironolactone for severe chronic heart failure? An analysis of the COPERNICUS study. American Heart Journal, 151(1), pp. 55-61. St. Louis, Mo.: Elsevier 10.1016/j.ahj.2005.03.054

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BACKGROUND: The beneficial effects of beta-blockers and aldosterone receptor antagonists are now well established in patients with severe systolic chronic heart failure (CHF). However, it is unclear whether beta-blockers are able to provide additional benefit in patients already receiving aldosterone antagonists. We therefore examined this question in the COPERNICUS study of 2289 patients with severe CHF receiving the beta1-beta2/alpha1 blocker carvedilol compared with placebo. METHODS: Patients were divided post hoc into subgroups according to whether they were receiving spironolactone (n = 445) or not (n = 1844) at baseline. Consistency of the effect of carvedilol versus placebo was examined for these subgroups with respect to the predefined end points of all-cause mortality, death or CHF-related hospitalizations, death or cardiovascular hospitalizations, and death or all-cause hospitalizations. RESULTS: The beneficial effect of carvedilol was similar among patients who were or were not receiving spironolactone for each of the 4 efficacy measures. For all-cause mortality, the Cox model hazard ratio for carvedilol compared with placebo was 0.65 (95% CI 0.36-1.15) in patients receiving spironolactone and 0.65 (0.51-0.83) in patients not receiving spironolactone. Hazard ratios for death or all-cause hospitalization were 0.76 (0.55-1.05) versus 0.76 (0.66-0.88); for death or cardiovascular hospitalization, 0.61 (0.42-0.89) versus 0.75 (0.64-0.88); and for death or CHF hospitalization, 0.63 (0.43-0.94) versus 0.70 (0.59-0.84), in patients receiving and not receiving spironolactone, respectively. The safety and tolerability of treatment with carvedilol were also similar, regardless of background spironolactone. CONCLUSION: Carvedilol remained clinically efficacious in the COPERNICUS study of patients with severe CHF when added to background spironolactone in patients who were practically all receiving angiotensin-converting enzyme inhibitor (or angiotensin II antagonist) therapy. Therefore, the use of spironolactone in patients with severe CHF does not obviate the necessity of additional treatment that interferes with the adverse effects of sympathetic activation, specifically beta-blockade.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Mohacsi, Paul

ISSN:

0002-8703

ISBN:

16368292

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

02 Nov 2018 10:22

Publisher DOI:

10.1016/j.ahj.2005.03.054

PubMed ID:

16368292

Web of Science ID:

000234485100009

URI:

https://boris.unibe.ch/id/eprint/21956 (FactScience: 20547)

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