Effects of Losartan on Cardiovascular Morbidity and Mortality in Patients With Isolated Systolic Hypertension and Left Ventricular Hypertrophy: A Losartan Intervention For Endpoint Reduction (LIFE) Substudy

• Published in: JAMA : the journal of the American Medical Association 2002-09, Vol.288 (12), p.1491-1498
• Main Authors: Kjeldsen, Sverre E, Dahlöf, Björn, Devereux, Richard B, Julius, Stevo, Aurup, Peter, Edelman, Jonathan, Beevers, Gareth, de Faire, Ulf, Fyhrquist, Frej, Ibsen, Hans, Kristianson, Krister, Lederballe-Pedersen, Ole, Lindholm, Lars H, Nieminen, Markku S, Omvik, Per, Oparil, Suzanne, Snapinn, Steven, Wedel, Hans, for the LIFE Study Group
• Format: Article
• Language: English
• Subjects: Aged; Antihypertensive agents; Antihypertensive Agents - therapeutic use; Atenolol - therapeutic use; Biological and medical sciences; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - mortality; Cardiovascular system; Double-Blind Method; Female; Humans; Hydrochlorothiazide - therapeutic use; Hypertension - drug therapy; Hypertrophy, Left Ventricular - drug therapy; Losartan - therapeutic use; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Myocardial Infarction - epidemiology; Pharmacology. Drug treatments; Proportional Hazards Models; Stroke - epidemiology; Systole; Treatment Outcome
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.288.12.1491

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