Effects of losartan or atenolol in hypertensive patients without clinically evident vascular disease: a substudy of the LIFE randomized trial.
BACKGROUND
Cardiovascular morbidity and mortality are reduced by treatment with the angiotensin II AT(1)-receptor antagonist losartan compared with conventional treatment with the beta-blocker atenolol in patients with hypertension and electrocardiogram-defined left ventricular hypertrophy, many of whom had known vascular disease.


OBJECTIVE
To determine whether losartan reduces cardiovascular event rates in lower-risk hypertensive patients without clinically evident vascular disease.


METHODS
Subgroup analysis of a randomized trial.


METHODS
The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study.


METHODS
6886 men and women (57% women) 55 to 80 years of age (average, 66 years) with essential hypertension (sitting blood pressure, 160 to 200/95 to 115 mm Hg [average, 174/98 mm Hg]) and electrocardiogram-defined left ventricular hypertrophy who did not have clinically evident vascular disease.


METHODS
Patients were randomly assigned to once-daily double-blind treatment with losartan or atenolol.


METHODS
An end point committee ascertained end points (cardiovascular death, stroke, or myocardial infarction).


RESULTS
Blood pressure was reduced similarly by losartan and atenolol. The primary composite end point occurred in 282 losartan-treated patients (17.5 per 1000 patient-years) and 355 atenolol-treated patients (21.8 per 1000 patient-years; relative risk, 0.81 [95% CI, 0.69 to 0.95]; P = 0.008). Cardiovascular death occurred in 103 losartan-treated patients and 132 atenolol-treated patients (relative risk, 0.80 [CI, 0.62 to 1.04]; P = 0.092), stroke (nonfatal and fatal) occurred in 125 losartan-treated patients and 193 atenolol-treated patients (relative risk, 0.66 [CI, 0.53 to 0.82]; P < 0.001), and myocardial infarction (nonfatal and fatal) occurred in 110 losartan-treated patients and 100 atenolol-treated patients (relative risk, 1.14 [CI, 0.87 to 1.49]; P > 0.2). New-onset diabetes occurred less often in patients treated with losartan (n = 173) than in patients treated with atenolol (n = 254) (relative risk, 0.69 [CI, 0.57 to 0.84]; P < 0.001). Benefits of losartan treatment were numerically smaller, but not significantly so, in patients with preexisting vascular disease.


CONCLUSIONS
In hypertensive patients without clinically evident vascular disease, losartan was more effective than atenolol in preventing cardiovascular morbidity and death, predominantly stroke, independent of blood pressure reduction.
Devereux
Richard B
RB
Weill Medical College of Cornell University, New York, New York, USA. rbdevere@med.cornell.edu
Dahlöf
Björn
B
Kjeldsen
Sverre E
SE
Julius
Stevo
S
Aurup
Peter
P
Beevers
Gareth
G
Edelman
Jonathan M
JM
de Faire
Ulf
U
Fyhrquist
Frej
F
Helle Berg
Sigrid
S
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
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000150:complications*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001262:Atenolol; D019808:Losartan