Although consequences in patients ...

Although consequences in patients with chronic heart failure (CHF) have improved lately because of the increasingly widespread use of beta blocker and angiotensin-converting enzyme (ACE) inhibitors, patients remain at increased risk of hospital admission and cardiovascular death. In addition, CHF is the main reason for hospital admission in older adults, and its significance is look fored to increase as the population ages. In the search for improved therapies for CHF angiotensin II pattern 1 receptor blockers (ARBs) could experience valuable, especially in patients who cannot tolerate ACE inhibitors. Pfeffer and colleagues reported the rises of large international trials of the ARB candesartan in patients with CHF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) study

They studied adult patients at 618 sites in six countries who had symptomatic CHF of strange York Heart Association (NYHA) class II to IV of at least four weeks' duration. Patients with limited two-year survival were exclud from the application of mind Exclusion criteria included the following conditions: elevated plains of serum potassium or creatinine; bilateral renal artery stenosis; hypotension; new myocardial infarction (MI); cardiac surgery or stroke; or use of an ARB within the previous pair weeks. Eligible patients were assigned to different studies based upon left-ventricular ejection fraction (LVEF) and experience with ACE inhibitors. Patients with LVEF greater than 40 percent formed the CHARM-Preserved arrange while patients with 40 percent or lower LVEF who were being treated with an ACE inhibitor were assigned to the CHARM-Added dispose and those with 40 percent or lower LVEF who were not receiving an ACE inhibitor because of previous intolerance were assigned to the CHARM-Alternative group

All patients were assigned randomly to treatment with candesartan or placebo. Starting dosages of candesartan were 4 mg or 8 mg daily, and the dosage was increased as tolerated to a target dosage of 32 mg daily. one time the drug dosage had been titrated, patients were followed each four months for at least pair years. Use of conventional CHF therapy continued during the cogitation at the physicians' discretion. Although overall mortality was the primary issue other outcomes monitored included cardiovascular death, hospital admission for CHF MI, blow cardiac revascularization procedure, and new-onset diabetes.

The 3803 patients treated with candesartan and the 3796 given placebo were comparable in all important refer tos During the median 37.7 month of follow-up 886 candesartan-treated patients (23 percent) and 945 placebo-treated patients (25 percent) died of any cause. This lower rate of mortality among patients treated with candesartan was attributable to fewer cardiovascular deaths (691 [18 percent] compared with 769 [20 percent] in the placebo group) particularly during the first year of treatment.

Hospital admissions for CHF were reduc significantly in candesartan-treated patients (1454 compared with 2010 placebo-treated patients) and significantly fewer candesartan-treated patients had sum of two units or more admissions for CHF (9 percent compared with 12 percent for placebo). The overall reduction in risk of death or hospital admission with candesartan treatment was similar in men and women and was equivalent in the 1736 patients 75 years or older compared with the younger patients. Effectiveness also was similar in patients with LVEF above or below 40 percent across all NYHA classes of CHF and irrespective of the personality of diabetes. By six month 63 percent of patients in the candesartan collection had achieved the target dosage, yet 11 percent had discontinued the medication compared with 7 percent of patients who had discontinued placebo. by the agency of the end of the meditation 23 percent of candesartan-treated survivors and 19 percent of placebo-treated patients had discontinued the medication. Laboratory abnormalities were the greatest in quantity common reasons given for discontinuation.

The authors infer that candesartan therapy is associated with a small on the other hand significant reduction in overall death and hospital admission in patients with CHF regardless of previous treatment or ejection fraction.

ANNE D WALLING, MD

Pfeffer MA, et al. forces of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet September 6 2003; 362:759-66

EDITOR'S NOTE: When The Lancet publishes four individual "fast-track" articles and a commentary (1) upon the results of a single consideration a major shift in therapy is underway. In addition to the above "overall" cogitation articles have been published in succession the subgroup of patients with preserv ventricular function, and brace articles were published on subgroup with reduc ventricular function (one cluster intolerant of ACE inhibitors and undivided group tolerant). In all cases, significant on the contrary sometimes modest benefits were obtained, and adverse efficiencys were documented. A summary of this rather overwhelming wealth of information ends that over three years, ARB therapy precludeed one death per 63 patients treated, single in kind hospitalization per 23 patients treated, and common new case of diabetes by 71 patients treated. The author attract favor tos adding ARBs to optimal popular therapy (i.e., ACE inhibitors, beta blocker possibly spironolactone) in patients with CHF who have ejection fractions of 40 percent or les Use of ARBs also is make acceptableed in patients with CHF who are intolerant of ACE inhibitors. In patients with CHF who have ejection fractions greater than 40 percent the retiring risk reduction must be considered against adverse weights tolerability, and other factors onward an individual basis.