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Relationship of dos...
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
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McMurray, J. J. (author)
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Young, J. B. (author)
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Dunlap, M. E. (author)
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Granger, C. B. (author)
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Hainer, J. (author)
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Michelson, E. L. (author)
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Earle, S. (author)
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Olofsson, B. (author)
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- Ostergren, J. (author)
- Karolinska Institutet
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Yusuf, S. (author)
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- Swedberg, Karl, 1944 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för akut och kardiovaskulär medicin,Institute of Medicine, Department of Emergeny and Cardiovascular Medicine
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Pfeffer, M. A. (author)
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(creator_code:org_t)
- Elsevier BV, 2006
- 2006
- English.
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In: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 151:5, s. 985-91
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- Aged
- Angiotensin II Type 1 Receptor Blockers/adverse effects/*therapeutic use
- dosage/therapeutic use
- Benzimidazoles/adverse effects/*therapeutic use
- Dose-Response Relationship
- Drug
- Drug Therapy
- Combination
- Female
- Heart Failure
- Congestive/*drug therapy/*mortality/therapy
- Hospitalization/statistics & numerical data
- Humans
- Male
- Middle Aged
- Proportional Hazards Models
- Randomized Controlled Trials
- Tetrazoles/adverse effects/*therapeutic use
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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McMurray, J. J.
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Young, J. B.
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Dunlap, M. E.
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Granger, C. B.
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Hainer, J.
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Michelson, E. L.
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show more...
-
Earle, S.
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Olofsson, B.
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Ostergren, J.
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Yusuf, S.
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Swedberg, Karl, ...
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Pfeffer, M. A.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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American heart j ...
- By the university
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University of Gothenburg
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Karolinska Institutet