PMID- 15492298
OWN - NLM
STAT- MEDLINE
DCOM- 20050512
LR  - 20211203
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 110
IP  - 17
DP  - 2004 Oct 26
TI  - 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.
PG  - 2618-26
AB  - 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.
FAU - Young, James B
AU  - Young JB
AD  - Division of Medicine, The Cleveland Clinic Foundation and Kaufman Center for 
      Heart Failure, 9500 Euclid Avenue T-13, Cleveland, OH 44195, USA. youngj@ccf.org
FAU - Dunlap, Mark E
AU  - Dunlap ME
FAU - Pfeffer, Marc A
AU  - Pfeffer MA
FAU - Probstfield, Jeffrey L
AU  - Probstfield JL
FAU - Cohen-Solal, Alain
AU  - Cohen-Solal A
FAU - Dietz, Rainer
AU  - Dietz R
FAU - Granger, Christopher B
AU  - Granger CB
FAU - Hradec, Jaromir
AU  - Hradec J
FAU - Kuch, Jerzy
AU  - Kuch J
FAU - McKelvie, Robert S
AU  - McKelvie RS
FAU - McMurray, John J V
AU  - McMurray JJ
FAU - Michelson, Eric L
AU  - Michelson EL
FAU - Olofsson, Bertil
AU  - Olofsson B
FAU - Ostergren, Jan
AU  - Ostergren J
FAU - Held, Peter
AU  - Held P
FAU - Solomon, Scott D
AU  - Solomon SD
FAU - Yusuf, Salim
AU  - Yusuf S
FAU - Swedberg, Karl
AU  - Swedberg K
CN  - Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity 
      (CHARM) Investigators and Committees
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20041018
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Benzimidazoles)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Tetrazoles)
RN  - S8Q36MD2XX (candesartan)
SB  - IM
CIN - Circulation. 2004 Oct 26;110(17):2559-61. PMID: 15505109
CIN - ACP J Club. 2005 May-Jun;142(3):60. PMID: 15862059
MH  - Aged
MH  - Angiotensin II Type 1 Receptor Blockers/*antagonists & inhibitors
MH  - Benzimidazoles/*therapeutic use
MH  - Biphenyl Compounds
MH  - Cardiac Output, Low/diagnosis/*drug therapy/*mortality
MH  - Chronic Disease
MH  - Female
MH  - Hospitalization
MH  - Humans
MH  - Male
MH  - Randomized Controlled Trials as Topic
MH  - Stroke Volume
MH  - Systole
MH  - Tetrazoles/*therapeutic use
MH  - Ventricular Dysfunction, Left/diagnosis/*drug therapy/*mortality
EDAT- 2004/10/20 09:00
MHDA- 2005/05/13 09:00
CRDT- 2004/10/20 09:00
PHST- 2004/10/20 09:00 [pubmed]
PHST- 2005/05/13 09:00 [medline]
PHST- 2004/10/20 09:00 [entrez]
AID - 01.CIR.0000146819.43235.A9 [pii]
AID - 10.1161/01.CIR.0000146819.43235.A9 [doi]
PST - ppublish
SO  - Circulation. 2004 Oct 26;110(17):2618-26. doi: 
      10.1161/01.CIR.0000146819.43235.A9. Epub 2004 Oct 18.