Effects of losartan or atenolol in hypertensive patients without clinically evident vascular disease: a substudy of the LIFE randomized trial

Ann Intern Med. 2003 Aug 5;139(3):169-77. doi: 10.7326/0003-4819-139-3-200308050-00006.


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.

Design: Subgroup analysis of a randomized trial.

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

Patients: 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.

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

Measurements: 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents / therapeutic use*
  • Atenolol / therapeutic use*
  • Cardiovascular Diseases / prevention & control*
  • Double-Blind Method
  • Electrocardiography
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertrophy, Left Ventricular / complications*
  • Losartan / therapeutic use*
  • Male
  • Middle Aged


  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Atenolol
  • Losartan