Diuretic-based treatment and cardiovascular events in patients with mild renal dysfunction enrolled in the systolic hypertension in the elderly program

Background: It is expected that the treatment of hypertension in patients with renal disease decreases the risk of cardiovascular events, but the evidence in these patients is lacking. Objective: To assess the effect of diuretic-based treatment on cardiovascular events in patients with isolated systolic hypertension and renal dysfunction. Methods: A total of 4336 persons aged 60 years and older with systolic blood pressures of 160 mm Hg and higher and diastolic blood pressures of less than 90 mm Hg were randomly assigned to receive either placebo or chlorthalidone (12.5-25.0 mg/d), with the addition of atenolol (25-50 mg/d) or reserpine (0.05-0.10 mg/d) if needed, and observed for 5 years. The risk of first-occurring cardiovascular events, including stroke, transient ischemic attack, myocardial infarction, heart failure, coronary artery bypass surgery, angioplasty, aneurysm, endarterectomy, sudden death, or rapid death, was stratified according to baseline serum creatinine levels (35.4-84.0, 84.1-101.6, 101.7-119.3, and 119.4-212.2 mu mol/L [0.4-0.9, 1.0-1.1, 1.2-1.3, and 1.4-2.4 mg/dL]). Results: Systolic blood pressure reduction was not affected by baseline serum creatinine levels. Active treatment did not affect the risk of serum creatinine levels becoming elevated during follow-up. The risk of hypokalemia with active treatment decreased significantly with increasing baseline serum creatinine levels. In the 4 baseline serum creatinine groups, the relative risk (95% confidence interval) of cardiovascular events developing with active treatment was 0.73 (0.54-0.97), 0.63 (0.49-0.82), 0.62 (0.44-0.87), and 0.59 (0.38-0.91), The results were similar for the outcomes of stroke or coronary artery events and in analyses stratified by sex or age. Conclusion: Diuretic-based treatment of patients with isolated systolic hypertension prevents the development of cardiovascular events in older persons with mild renal dysfunction.