Cardiovascular Morbidity and Mortality in Patients with Diabetes in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE): A Randomised Trial against Atenolol. - LIFE Diabetic Substudy

Description:

Is angiotensin II receptor blockade (losartan) better than beta-blockers (atenolol) for reducing cardiovascular morbidity and mortality in hypertensive diabetics?

Study Design

Study Design:

Patients Screened: 10,778
Patients Enrolled: 9193 (1195 in this substudy)
Mean Follow Up: 4.8 years
Mean Patient Age: 55-80 Years. Mean 67 years
Female: 54%

Patient Populations:

1) Diagnosis of diabetes mellitus 2) Essential hypertension (sitting blood pressure 160-200/95-115 mm Hg) 3) LVH determined by Cornell Voltage Product criteria or Sokolow-Lyon Voltage

Exclusions:

1) Secondary hypertension 2) Stroke or myocardial infarction within previous 6 months 3) Angina requiring treatment with beta-blocker or calcium channel blocker 4) Heart failure or LVEF <40% 5) Condition requiring treatment with angiotensin II receptor antagonist, atenolol, or ACE inhibitor

Secondary Endpoints:

1) Regression of LVH 2) Total mortality 3) Stroke 4) Myocardial infarction 5) Cardiovascular death 6) Subgroup analysis of diabetics, patients with essential 7) hypertension and atrial fibrillation

Drug/Procedures Used:

In the LIFE study reviewed above, 1195 of the hypertensive subjects with evidence for LVH were diabetics. 586 were randomly assigned to losartan and 609 to atenolol. The anti-hypertensive treatment algorithm for diabetes was identical to the entire study. Patients were followed for 4 years with the primary endpoint CV events (death, MI, stroke).

Principal Findings:

The average age was 67 yrs, BP 177/96 mmHg, 53% were women, and 35% had vascular disease (24% CAD, 12% CVD, 7% PVOD). In the diabetic subgroup of the LIFE trial, patients had larger body mass index, higher rates of preexisting coronary disease, systolic blood pressure, higher blood glucoses and lower diastolic blood pressures with lower rates of smoking compared to the overall cohort. On-study about 60% were on sulfonylureas, 38% metformin, 28% insulin, 31% statins, and 47% ASA. Mean BP fell similarly by about 18/11 mmHg. The primary composite endpoint occurred in 17.6% on losartan and 22.8% on atenolol, RR 0.76, p=0.01. 6% losartan and 10% atenolol patients died from cardiovascular disease (0.62, 0.41-92, p=0.019). Total mortality was lower in diabetics treated with losartan compared to atenolol (11% v. 17%; p=0.002[RR 0.61, 95% CI 0.45-0.84]). LVH regression was greater in patients in patients treated with losartan compared to atenolol (p<0.0001). There was no difference in fatal or non-fatal MI or strokes.

Interpretation:

Among diabetic patients with hypertension and LVH, Losartan was associated with a significant reduction in CV morbidity and mortality. The results extend the observations from other studies and support the use of both ACEi and ARBs in hypertensive diabetics with and without established CVD. This study was conducted in a particularly high-risk cohort in whom LVH was an entry criterion.

References:

Lindholm LH, Ibsen H, Dahof B, et al for the LIFE Study Group. 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;359:1004-10.

Clinical Topics: Prevention, Hypertension, Smoking

Keywords: Hypertrophy, Left Ventricular, Losartan, Stroke, Receptors, Angiotensin, Insulins, Smoking, Body Mass Index, Metformin, Blood Glucose, Hypertension, Diabetes Mellitus


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