Losartan Intervention For Endpoint Reduction in Hypertension - LIFE LVH Substudy

Description:

Comparison of losartan to atenolol in patients with essential hypertension and left ventricular hypertrophy

Hypothesis:

Losartan will reduce the primary composite endpoint of stroke, myocardial infarction or cardiovascular death to a greater extent compared to atenolol in patients with essential hypertension and left ventricular hypertrophy

Study Design

Study Design:

Patients Screened: 10,778
Patients Enrolled: 9193
Mean Follow Up: 4.8 years
Mean Patient Age: 55-80 Years
Female: 54%

Patient Populations:

1) Essential hypertension (sitting blood pressure 160-200/95-115 mm Hg) 2) 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:

Losartan 50 mg/day compared to atenolol 50 mg/day titrated upward to SBP <140 mm Hg

Concomitant Medications:

HCTZ added after 2 months if SBP >140 mm Hg, other agents added if losartan or atenolol dose 100 mg/day, HCTZ dose 25 mg/day and SBP >140 mm Hg

Principal Findings:

The primary composite endpoint occurred in 508 losartan (23.8 per 1000 patient-years) and 588 atenolol patients (27.9 per 1000 patient-years; relative risk 0.87, 95% CI 0.77-0.98, p=0.021). 204 losartan and 234 atenolol patients died from cardiovascular disease (0.89, 0.73-1.07, p=0.206); 232 and 309, respectively, had fatal or non-fatal stroke (0.75, 0.63-0.89, p=0.001); and myocardial infarction (non-fatal and fatal) occurred in 198 and 188, respectively (1.07, 0.88-1.31, p=0.491). These reductions were independent of blood pressure decreases. Losartan was better tolerated than atenolol. A recent report evaluated the effect of LVH in this cohort. There was a significant decrease in left ventricular mass over the course of the study in both arms with the magnitude of reduction being greater in the losartan group (p=0.02). When stratified for left ventricular hypertrophy, the composite endpoint was significantly lower in patients without LVH. (p=0.008; [HR 0.58, 95% CI 0.38-0.68]). Cardiovascular mortality and stroke but not myocardial infarction were each individually lower in patients without LVH. Losartan also led to a decrease in left atrial size compared to atenolol and afer adjusting for age and blood pressure reduction, the stroke rate in patients with atrial fibrillation was lower in patients treated with losartan (p=0.018; [HR 0.51, 95% CI 0.29-0.89].

Interpretation:

Losartan was associated with improved cardiovascular outcomes in including cardiovascular death and stroke when compared to atenolol in patients with essential hypertension and left ventricular hypertrophy. Despite a larger decrease in left ventricular hypertrophy with losartan compared to atenolol, there was no significant decrease in myocardial infarction.

References:

Dahlof B. Lancet 2002; 359:996-1003. Linholm LH. Lancet 2002; 359:1004-1010. Update presented by B. Dahlof at the Annual Meeting of the European Society of Cardiology, September 4, 2002

Clinical Topics: Prevention, Hypertension

Keywords: Hypertrophy, Left Ventricular, Losartan, Risk, Myocardial Infarction, Stroke, Blood Pressure, Hypertension


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