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.
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.
Kjeldsen
Sverre E
SE
Department of Internal Medicine, Dividsion of Hypertension, University of Michigan, Ann Arbor, USA.
Dahlöf
Björn
B
Devereux
Richard B
RB
Julius
Stevo
S
Aurup
Peter
P
Edelman
Jonathan
J
Beevers
Gareth
G
de Faire
Ulf
U
Fyhrquist
Frej
F
Ibsen
Hans
H
Kristianson
Krister
K
Lederballe-Pedersen
Ole
O
Lindholm
Lars H
LH
Nieminen
Markku S
MS
Omvik
Per
P
Oparil
Suzanne
S
Snapinn
Steven
S
Wedel
Hans
H
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
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D001262:Atenolol; D019808:Losartan