Although angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in heart failure, their widespread use in eligible patients has been limited by adverse reactions such as cough, angioedema, renal dysfunction and hypotension. Increasing levels of bradykinin have been blamed for these adverse reactions, leading to the development of highly specific second-generation ACE inhibitors that block the receptor without increasing bradykinin levels. Pitt and associates summarized results of the ELITE (Evaluation of Losartan in the Elderly) study, an international trial comparing losartan with captopril in patients aged 65 or older with symptomatic heart failure.
The 722 patients studied had symptomatic heart failure rated as New York Heart Association class II to IV and ejection fractions of 40 percent or less but had not previously been treated with ACE inhibitors. Exclusion criteria included uncontrolled hypertension, cardiac arrhythmia, recent myocardial infarction or ischemia, elevated levels of serum creatinine or potassium, or uncontrolled medical conditions such as diabetes or thyroid disease. After assessment and a two-week run-in treatment with placebo, patients were randomly assigned to treatment with either losartan or captopril. Each drug was titrated, up to 50 mg three times daily for captopril plus placebo, or up to 50 mg once daily for losartan plus placebo. Patients were assessed clinically every week during the drug titration period, then at three-month intervals. Laboratory monitoring of creatinine and potassium measurements were taken at three, six and 12 weeks and then every three months.
The 352 patients randomized to receive losartan were comparable to the 370 randomized to receive captopril, and both groups had similar high rates of use of concomitant therapy such as diuretics, digitalis and vasodilating agents. In both groups, 10.5 percent of patients developed persistent elevations of serum creatinine. Patients treated with losartan showed an unexpected, significant reduction of 32 percent in rates of death and/or hospital admission related to heart failure. These outcomes occurred in 33 (9.4 percent) of patients treated with losartan, compared with 49 (13.2 percent) of those treated with captopril. Hospital admission for any reason was also reduced in the group treated with losartan (22.2 percent compared with 29.7 percent). In addition, 111 (30 percent) of patients in the captopril group discontinued treatment or died, compared with 65 (18.5 percent) of those receiving losartan. Fourteen withdrawals in the captopril group were attributed to cough and nine to worsening heart failure, compared with no withdrawals attributed to cough and three withdrawals attributed to heart failure in the losartan group.
The authors conclude that losartan was better tolerated than captopril and resulted in reduced rates of hospital admission and death but similar rates of renal dysfunction.
Pitt B, et al. Randomized trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997;349: 747-52.
COPYRIGHT 1997 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group
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