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.
Abstract | BACKGROUND: 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:
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Authors | James B Young, Mark E Dunlap, Marc A Pfeffer, Jeffrey L Probstfield, Alain Cohen-Solal, Rainer Dietz, Christopher B Granger, Jaromir Hradec, Jerzy Kuch, Robert S McKelvie, John J V McMurray, Eric L Michelson, Bertil Olofsson, Jan Ostergren, Peter Held, Scott D Solomon, Salim Yusuf, Karl Swedberg, Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Investigators and Committees |
Journal | Circulation
(Circulation)
Vol. 110
Issue 17
Pg. 2618-26
(Oct 26 2004)
ISSN: 1524-4539 [Electronic] United States |
PMID | 15492298
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Benzimidazoles
- Biphenyl Compounds
- Tetrazoles
- candesartan
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Topics |
- Aged
- Angiotensin II Type 1 Receptor Blockers
(antagonists & inhibitors)
- Benzimidazoles
(therapeutic use)
- Biphenyl Compounds
- Cardiac Output, Low
(diagnosis, drug therapy, mortality)
- Chronic Disease
- Female
- Hospitalization
- Humans
- Male
- Randomized Controlled Trials as Topic
- Stroke Volume
- Systole
- Tetrazoles
(therapeutic use)
- Ventricular Dysfunction, Left
(diagnosis, drug therapy, mortality)
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