Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE)

BACKGROUND: To determine whether specific angiotensin II receptor blockade with losartan offers safety and efficacy advantages in the treatment of heart failure over angiotensin-converting-enzyme (ACE) inhibition with captopril, the ELITE study compared losartan with captopril in older heart-failure patients. METHODS: We randomly assigned 722 ACE inhibitor naive patients (aged 65 years or more) with New York Heart Association (NYHA) class II-IV heart failure and ejection fractions of 40% or less to double-blind losartan (n = 352) titrated to 50 mg once daily or captopril (n = 370) titrated to 50 mg three times daily, for 48 weeks. The primary endpoint was the tolerability measure of a persisting increase in serum creatinine of 26.5 mumol/L or more (> or = 0.3 mg/dL) on therapy; the secondary endpoint was the composite of death and/or hospital admission for heart failure; and other efficacy measures were total mortality, admission for heart failure, NYHA class, and admission for myocardial infarction or unstable angina. FINDINGS: The frequency of persisting increases in serum creatinine was the same in both groups (10.5%). Fewer losartan patients discontinued therapy for adverse experiences (12.2% vs 20.8% for captopril, p = 0.002). No losartan-treated patients discontinued due to cough compared with 14 in the captopril group. Death and/or hospital admission for heart failure was recorded in 9.4% of the losartan and 13.2% of the captopril patients (risk reduction 32% [95% CI -4% to + 55%], p = 0.075). This risk reduction was primarily due to a decrease in all-cause mortality (4.8% vs 8.7%; risk reduction 46% [95% CI 5-69%], p = 0.035). Admissions with heart failure were the same in both groups (5.7%), as was improvement in NYHA functional class from baseline. Admission to hospital for any reason was less frequent with losartan than with captopril treatment (22.2% vs 29.7%). INTERPRETATION: In this study of elderly heart-failure patients, treatment with losartan was associated with an unexpected lower mortality than that found with captopril. Although there was no difference in renal dysfunction, losartan was generally better tolerated than captopril and fewer patients discontinued losartan therapy. A further trial, evaluating the effects of losartan and captopril on mortality and morbidity in a larger number of patients with heart failure, is in progress.

[Persisting hyperlipidemias as risk factors of diabetic macroangiopathy]. / Persistierende Hyperlipidämien als Risikofaktoren der diabetischen Makroangiopathie.

Severe forms of arterial occlusive diseases occurred more frequently in 11 insulin-treated diabetics with persisting hyperlipidemia than in 10 control subjects who were 11 years older. Triglycerides and cholesterol of total serum and of VLDL were 2-7 times higher (P less than 0.01); however, LDL-cholesterol was 2 times lower than in control subjects (P less than 0.025). HDL-cholesterol was not significantly different in either group. After insulin administration (81 U/die vs 37 U/die, P less than 0.00251), the increased lipids were only insignificantly reduced, while LDL-cholesterol and the ratio of LDL-/HDL-cholesterol was even increased (P less than 0.0025 and P less than 0.05). In contrast to control subjects, VLDL-cholesterol was positively correlated to the tolbutamide-induced insulin reserve (before insulin administration) and to the diurnal insulin dosage (after insulin administration) (P less than 0.01 and P less than 0.001). The results show that the atherosclerotic risk in diabetics with persisting hyperlipidemia is higher than in control subjects and that the risk is distinguished by increased VLDL-cholesterol in correlation with increased insulin concentrations. Since the atherosclerotic risk is even more accentuated by the fact that insulin administration increases LDL-cholesterol, insulin therapy must be observed carefully in these patients.