CLINICAL RESEARCH: HEART FAILURE
Influence of pretreatment systolic blood pressure on the effect of carvedilol in patients with severe chronic heart failure
The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study
Jean L. Rouleau, MD*,*,
Ellen B. Roecker, PhD ,
Michal Tendera, MD ,
Paul Mohacsi, MD ,
Henry Krum, MD||,
Hugo A. Katus, MD¶,
Michael B. Fowler, MD#,
Andrew J. S. Coats, MD**,
Alain Castaigne, MD,
Armin Scherhag, MD,
Terry L. Holcslaw, PhD,
Milton Packer, MD|||| for the COPERNICUS Study Group
* Montreal Heart Institute, University of Montreal, Montreal, Canada
University of Wisconsin, Madison, Wisconsin, USA
Silesian School of Medicine, Katowice, Poland
University Hospital, Bern, Switzerland
|| Monash University, Prahran, Victoria, Australia
¶ Medizinische Universitaetsklinik Heidelberg, Heidelberg, Germany
# Stanford University Medical Center, Stanford, California, USA
** University of Sydney, Sydney, Australia
Hospital Henri Mondor, Paris, France
F. Hoffmann-La Roche Ltd., Basel, Switzerland
GlaxoSmithKline Ltd., Philadelphia, Pennsylvania, USA
|||| College of Physicians and Surgeons, Columbia University, New York, New York, USA
Manuscript received June 23, 2003;
revised manuscript received October 20, 2003,
accepted November 18, 2003.
* Reprint requests and correspondence: Dr. Jean L. Rouleau, C.P. 6128, Succursale Centre-ville, Montreal, Quebec, H3C 3J7, Canada.
jean.rouleau{at}umontreal.ca
OBJECTIVES: We sought to evaluate the influence of pretreatment systolic blood pressure (SBP) on the efficacy and safety of carvedilol in patients with chronic heart failure (CHF).
BACKGROUND: Although beta-blockers reduce the risk of death in CHF, there is little reported experience with these drugs in patients with a low pretreatment SBP, who may respond poorly to beta-blockade.
METHODS: We studied 2,289 patients with severe CHF who participated in the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.
RESULTS: Compared with placebo, carvedilol improved the clinical status and reduced the risk of death and the combined risk of death or hospitalization for any reason, for a cardiovascular reason, or for worsening heart failure (p < 0.001 for all). The relative magnitude of these benefits did not vary as a function of the pretreatment SBP (all interaction: p > 0.10). However, because patients with the lowest SBP were at highest risk of an event, they experienced the greatest absolute benefit from treatment with carvedilol. The lower the pretreatment SBP, the more likely that patients would report an adverse event, be intolerant of high doses of the study drug, or require permanent withdrawal of treatment (p < 0.001 for all). However, these risks were primarily related to the severity of the underlying illness and not to treatment with carvedilol.
CONCLUSIONS: The current study provides little support for concerns about using beta-blockers (particularly those with vasodilatory actions) in patients with severe CHF who have a low SBP. Pretreatment blood pressure can identify patients who have the greatest need for risk reduction with carvedilol.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | BP | = blood pressure | | CHF | = chronic heart failure | | COPERNICUS | = Carvedilol Prospective Randomized Cumulative Survival trial | | HF | = heart failure | | SBP | = systolic blood pressure |
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