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

Henry Krum, Paul Mohacsi, Hugo A. Katus, Michael Tendera, Jean Lucien Rouleau, Michael B. Fowler, Andrew J. Coats, Ellen B. Roecker, Milton Packer

Research output: Contribution to journalArticle

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Abstract

Background: The beneficial effects of β-blockers and aldosterone receptor antagonists are now well established in patients with severe systolic chronic heart failure (CHF). However, it is unclear whether β-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 β12/ α1 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 β-blockade.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalAmerican Heart Journal
Volume151
Issue number1
DOIs
StatePublished - Jan 2006

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Spironolactone
Heart Failure
Hospitalization
Mineralocorticoid Receptor Antagonists
Placebos
Systolic Heart Failure
Mortality
Proportional Hazards Models
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II
carvedilol
Cause of Death
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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Are β-blockers needed in patients receiving spironolactone for severe chronic heart failure? An analysis of the COPERNICUS study. / Krum, Henry; Mohacsi, Paul; Katus, Hugo A.; Tendera, Michael; Rouleau, Jean Lucien; Fowler, Michael B.; Coats, Andrew J.; Roecker, Ellen B.; Packer, Milton.

In: American Heart Journal, Vol. 151, No. 1, 01.2006, p. 55-61.

Research output: Contribution to journalArticle

Krum, H, Mohacsi, P, Katus, HA, Tendera, M, Rouleau, JL, Fowler, MB, Coats, AJ, Roecker, EB & Packer, M 2006, 'Are β-blockers needed in patients receiving spironolactone for severe chronic heart failure? An analysis of the COPERNICUS study', American Heart Journal, vol. 151, no. 1, pp. 55-61. https://doi.org/10.1016/j.ahj.2005.03.054
Krum, Henry ; Mohacsi, Paul ; Katus, Hugo A. ; Tendera, Michael ; Rouleau, Jean Lucien ; Fowler, Michael B. ; Coats, Andrew J. ; Roecker, Ellen B. ; Packer, Milton. / Are β-blockers needed in patients receiving spironolactone for severe chronic heart failure? An analysis of the COPERNICUS study. In: American Heart Journal. 2006 ; Vol. 151, No. 1. pp. 55-61.
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abstract = "Background: The beneficial effects of β-blockers and aldosterone receptor antagonists are now well established in patients with severe systolic chronic heart failure (CHF). However, it is unclear whether β-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 β1-β2/ α1 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 β-blockade.",
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AU - Mohacsi, Paul

AU - Katus, Hugo A.

AU - Tendera, Michael

AU - Rouleau, Jean Lucien

AU - Fowler, Michael B.

AU - Coats, Andrew J.

AU - Roecker, Ellen B.

AU - Packer, Milton

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N2 - Background: The beneficial effects of β-blockers and aldosterone receptor antagonists are now well established in patients with severe systolic chronic heart failure (CHF). However, it is unclear whether β-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 β1-β2/ α1 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 β-blockade.

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