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Relationship of dose of background angiotensin-converting enzyme inhibitor to the benefits of candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial.

Publication ,  Journal Article
McMurray, JJV; Young, JB; Dunlap, ME; Granger, CB; Hainer, J; Michelson, EL; Earle, S; Olofsson, B; Ostergren, J; Yusuf, S; Swedberg, K ...
Published in: Am Heart J
May 2006

BACKGROUND: Whether an angiotensin receptor blocker is of benefit when added to a full dose of angiotensin-converting enzyme (ACE) inhibitor in heart failure (HF) is uncertain. METHODS: The effect of candesartan, compared with placebo, in 2548 patients randomized in the CHARM-Added trial was analyzed according to (i) ACE inhibitor dose at baseline, (ii) ACE inhibitor dose during follow-up, and (iii) combination treatment with ACE inhibitor and beta-blocker at baseline. The main outcome was the composite of cardiovascular death or HF hospitalization. RESULTS: The benefit of candesartan was not modified by the dose of ACE inhibitor. In all patients (n = 2548), the candesartan/placebo hazard ratio (HR) for the primary outcome was 0.85 (95% CI 0.75-0.96). In patients taking a guideline recommended dose of ACE inhibitor at baseline (n = 1291), this HR was 0.79 (95% CI 0.67-0.95; interaction P value .26). In patients taking a Food and Drug Administration-designated maximum dose of ACE inhibitor (n = 529), this HR was 0.75 (95% CI 0.57-0.98; interaction P value .29). The benefit of candesartan was preserved in patients taking beta-blockers in addition to a higher dose of ACE inhibitor and in patients maintaining a high dose of ACE inhibitor throughout follow-up. CONCLUSIONS: These clinical findings support the pharmacologic evidence that ACE inhibitors and angiotensin receptor blockers have distinct mechanisms of action and show that their combined use improves outcomes in patients with HF more than an evidence-based dose of ACE inhibitor alone.

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Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

May 2006

Volume

151

Issue

5

Start / End Page

985 / 991

Location

United States

Related Subject Headings

  • Tetrazoles
  • Randomized Controlled Trials as Topic
  • Proportional Hazards Models
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
  • Heart Failure
  • Female
  • Drug Therapy, Combination
 

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McMurray, J. J. V., Young, J. B., Dunlap, M. E., Granger, C. B., Hainer, J., Michelson, E. L., … CHARM Investigators, . (2006). Relationship of dose of background angiotensin-converting enzyme inhibitor to the benefits of candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial. Am Heart J, 151(5), 985–991. https://doi.org/10.1016/j.ahj.2006.02.028
McMurray, John J. V., James B. Young, Mark E. Dunlap, Christopher B. Granger, James Hainer, Eric L. Michelson, Steven Earle, et al. “Relationship of dose of background angiotensin-converting enzyme inhibitor to the benefits of candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial.Am Heart J 151, no. 5 (May 2006): 985–91. https://doi.org/10.1016/j.ahj.2006.02.028.
McMurray JJV, Young JB, Dunlap ME, Granger CB, Hainer J, Michelson EL, Earle S, Olofsson B, Ostergren J, Yusuf S, Swedberg K, Pfeffer MA, CHARM Investigators. Relationship of dose of background angiotensin-converting enzyme inhibitor to the benefits of candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial. Am Heart J. 2006 May;151(5):985–991.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

May 2006

Volume

151

Issue

5

Start / End Page

985 / 991

Location

United States

Related Subject Headings

  • Tetrazoles
  • Randomized Controlled Trials as Topic
  • Proportional Hazards Models
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
  • Heart Failure
  • Female
  • Drug Therapy, Combination