Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial.
BACKGROUND
Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements, neurohumoral activity, and left-ventricular remodelling when added to angiotensin-converting-enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). We aimed to find out whether these drugs improve clinical outcome.


METHODS
Between March, 1999, and November, 1999, we enrolled 2548 patients with New York Heart Association functional class II-IV CHF and left-ventricular ejection fraction 40% or lower, and who were being treated with ACE inhibitors. We randomly assigned patients candesartan (n=1276, target dose 32 mg once daily) or placebo (n=1272). At baseline, 55% of patients were also treated with beta blockers and 17% with spironolactone. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was done by intention to treat.


RESULTS
The median follow-up was 41 months. 483 (38%) patients in the candesartan group and 538 (42%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0.85 [95% CI 0.75-0.96], p=0.011; covariate adjusted p=0.010). Candesartan reduced each of the components of the primary outcome significantly, as well as the total number of hospital admissions for CHF. The benefits of candesartan were similar in all predefined subgroups, including patients receiving baseline beta blocker treatment.


CONCLUSIONS
The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction.
D000293:Adolescent; D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D002303:Cardiac Output, Low / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D002318:Cardiovascular Diseases / Q000401:mortality; D015897:Comorbidity; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D008297:Male; D010919:Placebos; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010919:Placebos; D013777:Tetrazoles; C081643:candesartan