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Mortality and morbi...
Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials
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Young, J. B. (author)
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Dunlap, M. E. (author)
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Pfeffer, M. A. (author)
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Probstfield, J. L. (author)
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Cohen-Solal, A. (author)
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Dietz, R. (author)
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Granger, C. B. (author)
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Hradec, J. (author)
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Kuch, J. (author)
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McKelvie, R. S. (author)
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McMurray, J. J. (author)
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Michelson, E. L. (author)
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Olofsson, B. (author)
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Ostergren, J. (author)
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Held, P. (author)
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Solomon, S. D. (author)
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Yusuf, S. (author)
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- Swedberg, Karl, 1944 (author)
- Gothenburg University,Göteborgs universitet,Hjärt-kärlinstitutionen,Cardiovascular Institute
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(creator_code:org_t)
- 2004
- 2004
- English.
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In: Circulation. - 1524-4539. ; 110:17, s. 2618-26
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Abstract
Subject headings
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- BACKGROUND: Patients with symptomatic chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) have a high risk of death and hospitalization for CHF deterioration despite therapies with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and even an aldosterone antagonist. To determine whether the angiotensin-receptor blocker (ARB) candesartan decreases cardiovascular mortality, morbidity, and all-cause mortality in patients with CHF and depressed LVEF, a prespecified analysis of the combined Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) low LVEF trials was performed. CHARM is a randomized, double-blind, placebo-controlled, multicenter, international trial program. METHODS AND RESULTS: New York Heart Association (NYHA) class II through IV CHF patients with an LVEF of < or =40% were randomized to candesartan or placebo in 2 complementary parallel trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low LVEF patients (2289 candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or CHF hospitalization for each trial, with all-cause mortality a secondary end point in the pooled analysis of the low LVEF trials. Of the patients in the candesartan group, 817 (35.7%) experienced cardiovascular death or a CHF hospitalization as compared with 944 (41.3%) in the placebo group (HR 0.82; 95% CI 0.74 to 0.90; P<0.001) with reduced risk for both cardiovascular deaths (521 [22.8%] versus 599 [26.2%]; HR 0.84 [95% CI 0.75 to 0.95]; P=0.005) and CHF hospitalizations (516 [22.5%] versus 642 [28.1%]; HR 0.76 [95% CI 0.68 to 0.85]; P<0.001). It is important to note that all-cause mortality also was significantly reduced by candesartan (642 [28.0%] versus 708 [31.0%]; HR 0.88 [95% CI 0.79 to 0.98]; P=0.018). No significant heterogeneity for the beneficial effects of candesartan was found across prespecified and subsequently identified subgroups including treatment with ACE inhibitors, beta-blockers, an aldosterone antagonist, or their combinations. The study drug was discontinued because of adverse effects by 23.1% of patients in the candesartan group and 18.8% in the placebo group; the reasons included increased creatinine (7.1% versus 3.5%), hypotension (4.2% versus 2.1%), and hyperkalemia (2.8% versus 0.5%), respectively (all P<0.001). CONCLUSIONS: Candesartan significantly reduces all-cause mortality, cardiovascular death, and heart failure hospitalizations in patients with CHF and LVEF < or =40% when added to standard therapies including ACE inhibitors, beta-blockers, and an aldosterone antagonist. Routine monitoring of blood pressure, serum creatinine, and serum potassium is warranted.
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/*antagonists & inhibitors
- Benzimidazoles/*therapeutic use
- Cardiac Output
- Low/diagnosis/*drug therapy/*mortality
- Chronic Disease
- Female
- Hospitalization
- Humans
- Male
- Randomized Controlled Trials
- Stroke Volume
- Systole
- Tetrazoles/*therapeutic use
- Ventricular Dysfunction
- Left/diagnosis/*drug therapy/*mortality
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Young, J. B.
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Dunlap, M. E.
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Pfeffer, M. A.
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Probstfield, J. ...
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Cohen-Solal, A.
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Dietz, R.
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show more...
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Granger, C. B.
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Hradec, J.
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Kuch, J.
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McKelvie, R. S.
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McMurray, J. J.
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Michelson, E. L.
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Olofsson, B.
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Ostergren, J.
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Held, P.
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Solomon, S. D.
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Yusuf, S.
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Swedberg, Karl, ...
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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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Circulation
- By the university
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University of Gothenburg