Cardiovascular Morbidity and Mortality in Patients With Diabetes in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE): A Randomised Trial Against Atenolol

Lancet. 2002 Mar 23;359(9311):1004-10. doi: 10.1016/S0140-6736(02)08090-X.

Abstract

Background: The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear. In prespecified analyses, we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients.

Methods: As part of the LIFE study, in a double-masked, randomised, parallel-group trial, we assigned a group of 1195 patients with diabetes, hypertension, and signs of left-ventricular hypertrophy (LVH) on electrocardiograms losartan-based or atenolol-based treatment. Mean age of patients was 67 years (SD 7) and mean blood pressure 177/96 mm Hg (14/10) after placebo run-in. We followed up patients for at least 4 years (mean 4.7 years [1.1]). We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality (cardiovascular death, stroke, or myocardial infarction).

Findings: Mean blood pressure fell to 146/79 mm Hg (17/11) in losartan patients and 148/79 mm Hg (19/11) in atenolol patients. The primary endpoint occurred in 103 patients assigned losartan (n=586) and 139 assigned atenolol (n=609); relative risk 0.76 (95% CI 0.58-.98), p=0.031. 38 and 61 patients in the losartan and atenolol groups, respectively, died from cardiovascular disease; 0.63 (0.42-0.95), p=0.028. Mortality from all causes was 63 and 104 in losartan and atenolol groups, respectively; 0.61 (0.45-0.84), p=0.002.

Interpretation: Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes, and LVH. Losartan seems to have benefits beyond blood pressure reduction.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists*
  • Antihypertensive Agents / therapeutic use*
  • Atenolol / therapeutic use*
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Complications*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / drug therapy*
  • Losartan / therapeutic use*
  • Male
  • Middle Aged
  • Regression Analysis

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Atenolol
  • Losartan