September 25, 2002JAMA442 citations
View Full PaperEffects of Losartan on Cardiovascular Morbidity and Mortality in Patients With Isolated Systolic Hypertension and Left Ventricular Hypertrophy
Structured PICO
Does losartan reduce the composite of cardiovascular death, stroke, or myocardial infarction compared to atenolol in patients with isolated systolic hypertension and ECG-LVH?
P
Population
1,326 men and women aged 55 through 80 years (mean age 70) with isolated systolic hypertension (systolic blood pressure of 160 to 200 mm Hg and diastolic blood pressure of less than 90 mm Hg) and electrocardiographically documented left ventricular hypertrophy (ECG-LVH), recruited from 945 outpatient settings in the Nordic countries, the United Kingdom, and the United States.
I
Intervention
Once-daily losartan (n = 660) with hydrochlorothiazide as the second agent, administered for a mean of 4.7 years.
C
Comparator
Once-daily atenolol (n = 666) with hydrochlorothiazide as the second agent, administered for a mean of 4.7 years.
O
Outcome
Composite end point of cardiovascular death, stroke, or myocardial infarction.composite
In older patients with isolated systolic hypertension and ECG-LVH, losartan is superior to atenolol in reducing cardiovascular morbidity and mortality, particularly driven by reductions in stroke and cardiovascular death.
Abstract
CONTEXT: Drug intervention in placebo-controlled trials has been beneficial in isolated systolic hypertension. OBJECTIVE: To test the hypothesis that losartan improves outcome better than atenolol in patients with isolated systolic hypertension and electrocardiographically documented left ventricular hypertrophy (ECG-LVH). DESIGN: Double-blind, randomized, parallel-group study conducted in 1995-2001. SETTING AND PARTICIPANTS: A total of 1326 men and women aged 55 through 80 years (mean, 70 years) with systolic blood pressure of 160 to 200 mm Hg and diastolic blood pressure of less than 90 mm Hg (mean, 174/83 mm Hg) and ECG-LVH, recruited from 945 outpatient settings in the Nordic countries, the United Kingdom, and the United States. INTERVENTIONS: Patients were randomly assigned to receive once-daily losartan (n = 660) or atenolol (n = 666) with hydrochlorothiazide as the second agent in both arms, for a mean of 4.7 years. MAIN OUTCOME MEASURE: Composite end point of cardiovascular death, stroke, or myocardial infarction. RESULTS: Blood pressure was reduced by 28/9 and 28/9 mm Hg in the losartan and atenolol arms. The main outcome was reduced by 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 patient-years (relative risk RR, 0.75; 95% confidence interval CI, 0.56-1.01; P =.06, adjusted for risk and degree of ECG-LVH; unadjusted RR, 0.71; 95% CI, 0.53-0.95; P =.02). Patients receiving losartan had reductions in the following without a difference in the incidence of myocardial infarction: cardiovascular mortality (8.7 vs 16.9 events per 1000 patient-years; RR, 0.54; 95% CI, 0.34-0.87; P =.01), nonfatal and fatal stroke (10.6 vs 18.9 events per 1000 patient-years; RR, 0.60; 95% CI, 0.38-0.92; P =.02), new-onset diabetes (12.6 vs 20.1 events per 1000 patient-years; RR, 0.62; 95% CI, 0.40-0.97; P =.04), and total mortality (21.2 vs 30.2 events per 1000 patient-years; RR, 0.72; 95% CI, 0.53-1.00; P =.046). Losartan decreased ECG-LVH more than atenolol (P<.001) and was better tolerated. CONCLUSION: These data suggest that losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH.