title: 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.
abstract: BACKGROUND
  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).
  
  
  METHODS
  Double-blind, randomized, parallel-group study conducted in 1995-2001.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These data suggest that losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH.
authors.affiliation: Department of Internal Medicine, Dividsion of Hypertension, University of Michigan, Ann Arbor, USA.
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlöf
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.forename: Stevo
authors.initials: S
authors.lastname: Julius
authors.forename: Peter
authors.initials: P
authors.lastname: Aurup
authors.forename: Jonathan
authors.initials: J
authors.lastname: Edelman
authors.forename: Gareth
authors.initials: G
authors.lastname: Beevers
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.forename: Frej
authors.initials: F
authors.lastname: Fyhrquist
authors.forename: Hans
authors.initials: H
authors.lastname: Ibsen
authors.forename: Krister
authors.initials: K
authors.lastname: Kristianson
authors.forename: Ole
authors.initials: O
authors.lastname: Lederballe-Pedersen
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lindholm
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Per
authors.initials: P
authors.lastname: Omvik
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: Steven
authors.initials: S
authors.lastname: Snapinn
authors.forename: Hans
authors.initials: H
authors.lastname: Wedel
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D016016:Proportional Hazards Models; D020521:Stroke / Q000453:epidemiology; D013599:Systole; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D001262:Atenolol; D019808:Losartan