Background and Purpose—Epidemiologic studies have demonstrated that hypertension increases the risk of stroke, and clinical trials have shown that antihypertensive therapy reduces this risk. Incident stroke was significantly decreased by treatment in the Systolic Hypertension in Elderly Program (SHEP) Trial, but the reduction in fatal events was not statistically significant.

Methods—Vital status was determined for 4736 SHEP participants by matching to the National Death Index. We assessed the impact of antihypertensive treatment, stroke, and transient ischemic attacks (TIAs) during SHEP on long-term (mean, 14.3 years) mortality.

Results—Treatment with a chlorthalidone-based antihypertensive regimen significantly reduced the risk of cardiovascular death (adjusted relative risk [RR]=0.86; 95% CI, 0.76 to 0.98, P=0.026) in the SHEP cohort without a significant (P=0.39) interaction with stroke status. Patients who sustained a stroke during SHEP had significantly higher all-cause mortality at the 14.3-year mean follow-up: 65.6% compared with 40.6% among those free of stroke or TIA (adjusted RR=1.97; 95% CI, 1.67 to 2.33). They also were at higher risk for cardiovascular death (RR=2.00; 95% CI, 1.58 to 2.53) and stroke death (RR=2.94; 95% CI, 1.87 to 4.64). TIA was not significantly associated with increased total mortality (RR=1.13; 95% CI, 0.88 to 1.44), cardiovascular death (RR=1.30; 95% CI, 0.94 to 1.81), or stroke death (RR=1.76; 95% CI, 0.95 to 3.26).

Conclusions—In SHEP, chlorthalidone-based treatment reduced the risk of cardiovascular death after 14 years of extended follow-up. Nearly two thirds of elderly persons with isolated systolic hypertension who experienced stroke died within 14 years.