Context The Systolic Hypertension in the Elderly Program (SHEP) demonstrated
that treating isolated systolic hypertension in older patients decreased incidence
of total stroke, but whether all types of stroke were reduced was not evaluated.
Objective To investigate antihypertensive drug treatment effects on incidence
of stroke by type and subtype, timing of strokes, case-fatality rates, stroke
residual effects, and relationship of attained systolic blood pressure to
Design The SHEP study, a randomized, double-blind, placebo-controlled trial
began March 1, 1985, and had an average follow-up of 4.5 years.
Setting and Participants A total of 4736 men and women aged 60 years or older with isolated systolic
hypertension at 16 clinical centers in the United States.
Interventions Patients were randomly assigned to receive treatment with 12.5 mg/d
of chlorthalidone (step 1); either 25 mg/d of atenolol or 0.05 mg/d of reserpine
(step 2) could be added (n = 2365); or placebo (n = 2371).
Main Outcome Measures Occurrence, type and subtype, and timing of first strokes and stroke
fatalities; and change in stroke incidence for participants (whether in active
treatment or placebo groups) reaching study-specific systolic blood pressure
goal (decrease of at least 20 mm Hg from baseline to below 160 mm Hg) compared
with participants not reaching goal.
Results A total of 85 and 132 participants in the active treatment and placebo
groups, respectively, had ischemic strokes (adjusted relative risk [RR], 0.63;
95% confidence interval [CI], 0.48-0.82); 9 and 19 had hemorrhagic strokes
(adjusted RR, 0.46; 95% CI, 0.21-1.02); and 9 and 8 had strokes of unknown
type (adjusted RR, 1.05; 95% CI, 0.40-2.73), respectively. Four subtypes of
ischemic stroke were observed in active treatment and placebo group participants,
respectively, as follows: for lacunar, n = 23 and n = 43 (adjusted RR, 0.53;
95% CI, 0.32-0.88); for embolic, n = 9 and n = 16 (adjusted RR, 0.56; 95%
CI, 0.25-1.27); for atherosclerotic, n = 13 and n = 13 (adjusted RR, 0.99;
95% CI, 0.46-2.15); and for unknown subtype, n = 40 and n = 60 (adjusted RR,
0.64; 95% CI, 0.43-0.96). Treatment effect was observed within 1 year for
hemorrhagic strokes but was not seen until the second year for ischemic strokes.
Stroke incidence significantly decreased in participants attaining study-specific
systolic blood pressure goals.
Conclusions In this study, antihypertensive drug treatment reduced the incidence
of both hemorrhagic and ischemic (including lacunar) strokes. Reduction in
stroke incidence occurred when specific systolic blood pressure goals were