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A Losartan Intervention For Endpoint Reduction (LIFE) Substudy

Sverre E. Kjeldsen, MD; Björn Dahlöf, MD; Richard B. Devereux, MD; Stevo Julius, MD; Peter Aurup, MD; Jonathan Edelman, MD; Gareth Beevers, MD; Ulf de Faire, MD; Frej Fyhrquist, MD; Hans Ibsen, MD; Krister Kristianson, MD; Ole Lederballe-Pedersen, MD; Lars H. Lindholm, MD; Markku S. Nieminen, MD; Per Omvik, MD; Suzanne Oparil, MD; Steven Snapinn, PhD; Hans Wedel, PhD; for the LIFE Study Group

JAMA. 2002;288:1491-1498.

Context  Drug intervention in placebo-controlled trials has been beneficial in isolated systolic hypertension.

Objective  To test the hypothesis that losartan improves outcome better than atenolol in patients with isolated systolic hypertension and electrocardiographically documented left ventricular hypertrophy (ECG-LVH).

Design  Double-blind, randomized, parallel-group study conducted in 1995-2001.

Setting and Participants  A total of 1326 men and women aged 55 through 80 years (mean, 70 years) with systolic blood pressure of 160 to 200 mm Hg and diastolic blood pressure of less than 90 mm Hg (mean, 174/83 mm Hg) and ECG-LVH, recruited from 945 outpatient settings in the Nordic countries, the United Kingdom, and the United States.

Interventions  Patients were randomly assigned to receive once-daily losartan (n = 660) or atenolol (n = 666) with hydrochlorothiazide as the second agent in both arms, for a mean of 4.7 years.

Main Outcome Measure  Composite end point of cardiovascular death, stroke, or myocardial infarction.

Results  Blood pressure was reduced by 28/9 and 28/9 mm Hg in the losartan and atenolol arms. The main outcome was reduced by 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 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; unadjusted RR, 0.71; 95% CI, 0.53-0.95; P = .02). Patients receiving losartan had reductions in the following without a difference in the incidence of myocardial infarction: cardiovascular mortality (8.7 vs 16.9 events per 1000 patient-years; RR, 0.54; 95% CI, 0.34-0.87; P = .01), nonfatal and fatal stroke (10.6 vs 18.9 events per 1000 patient-years; RR, 0.60; 95% CI, 0.38-0.92; P = .02), new-onset diabetes (12.6 vs 20.1 events per 1000 patient-years; RR, 0.62; 95% CI, 0.40-0.97; P = .04), and total mortality (21.2 vs 30.2 events per 1000 patient-years; RR, 0.72; 95% CI, 0.53-1.00; P = .046). Losartan decreased ECG-LVH more than atenolol (P<.001) and was better tolerated.

Conclusion  These data suggest that losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH.

Author Affiliations: Department of Internal Medicine, Division of Hypertension, University of Michigan, Ann Arbor (Drs Kjeldsen and Julius); Department of Cardiology, Ullevaal University Hospital, Oslo, Norway (Dr Kjeldsen); Department of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden (Dr Dahlöf); Division of Cardiology, Cornell Medical Center, New York, NY (Dr Devereux); Merck & Co Inc, Whitehouse Station, NJ (Drs Aurup, Edelman, and Snapinn); City Hospital, Birmingham, England (Dr Beevers); Department of Medicine, Division of Cardiovascular Medicine, Karolinska University Hospital, Stockholm, Sweden (Dr de Faire); Department of Medicine (Dr Fyhrquist) and Division of Cardiology (Dr Nieminen), Helsinki University Central Hospital, Finland; Department of Internal Medicine, Glostrup University Hospital, Denmark (Dr Ibsen); Merck Research Laboratories Scandinavia, Stockholm, Sweden (Dr Kristianson); Department of Internal Medicine, Viborg Hospital, Denmark (Dr Lederballe-Pedersen); Umeå University, Sweden (Dr Lindholm); Division of Cardiology, Haukeland University Hospital, Bergen, Norway (Dr Omvik); Division of Cardiovascular Disease, University of Alabama, Birmingham (Dr Oparil); and the Nordic School of Public Health, Göteborg, Sweden (Dr Wedel).

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