Losartan Better Than Atenolol at Reducing Cardiovascular Risk

Laurie Barclay, MD

September 24, 2002

Sept. 25, 2002 — A randomized trial reported in the Sept. 25 issue of The Journal of the American Medical Association suggests that losartan may be better than atenolol in patients with isolated systolic hypertension (ISH) and left ventricular hypertrophy on electrocardiogram (ECG-LVH), despite similar reductions in blood pressure with both drugs.

"Losartan-based antihypertensive therapy was more effective than an atenolol-based treatment in preventing [cardiovascular (CV)] morbidity and mortality, especially stroke and CV death, in a large prespecified subset of LIFE [Losartan Intervention For Endpoint reduction] participants with ECG-LVH and ISH," write Sverre E. Kjeldsen, MD, from Ullevaal Hospital in Oslo, Norway, and colleagues. "In addition, losartan was associated with a lower incidence of new-onset diabetes and lower total mortality."

In this double-blind, parallel-group study conducted from 1995-2001, a total of 1,326 men and women aged 55 through 80 years were enrolled at 945 outpatient centers in the Nordic countries, the U.K., and the U.S. Systolic blood pressure was 160 to 200 mm Hg, diastolic blood pressure was less than 90 mm Hg, and all subjects had ECG-LVH. Patients received once-daily losartan or atenolol, plus hydrochlorothiazide as the second agent, for a mean of 4.7 years. Mean blood pressure decreased by 28/9 mm Hg in both groups. The composite endpoint of CV death, stroke, or myocardial infarction (MI) was reduced by 25% in the losartan group compared with the atenolol group (25.1 vs. 35.4 events per 1,000 patient-years; relative risk [RR], 0.75; 95% confidence interval [CI], 0.56-1.01; P=.06, adjusted for risk and degree of ECG-LVH).

Losartan decreased ECG-LVH more than atenolol did ( P<.001) and was better tolerated. Although the incidence of MI was unchanged, patients in the losartan group had lower CV mortality (8.7 vs. 16.9 events per 1,000 patient-years (RR, 0.54; 95% CI, 0.34-0.87; P=.01) and total mortality (21.2 vs. 30.2 events per 1,000 patient-years; RR, 0.72; 95% CI, 0.53-1.00; P=.046). Incidence of nonfatal and fatal stroke and new-onset diabetes were also lower in the losartan group.

Study limitations include its being a substudy of the LIFE study, and enrollment of predominantly white subjects at high risk because of ECG-LVH. The authors also acknowledge that beta-blockers may have different protective properties in younger patients than in older ones.

"It appears that in non-ISH patients, the main findings are reduced stroke and new-onset diabetes while in ISH patients losartan also lowers CV death and all-cause death," the authors write. "It is currently not known whether losartan is superior to diuretics or calcium channel blockers as a firstline treatment of ISH."

Merck & Co. supported this trial and has financial arrangements with some of its authors.

JAMA. 2002;288(12):1491-1498

Reviewed by Gary D. Vogin, MD