Systolic Hypertension in Elderly Program - SHEP


Pharmacologic therapy vs placebo in isolated systolic hypertension


Does anti-hypertensive drug therapy decrease the risk of stroke in individuals with isolated systolic hypertension?

Study Design

Study Design:

Patients Screened: 447,921
Patients Enrolled: 4736
NYHA Class: Not reported
Mean Follow Up: average 4.5 years
Mean Patient Age: average 71.6 years
Female: 57%
Mean Ejection Fraction: Evaluated in only 104 patients (see JAMA 1998;279:778-80)

Patient Populations:

≥60 years of age (14% black, 57% women) with SBP 160–219 mm Hg and DBP <90 mm Hg; 3,161 patients were taking anti-hypertensive drug(s).


Major cardiovascular diseases, other serious illnesses

Primary Endpoints:

Nonfatal and fatal (total) stroke

Secondary Endpoints:

Reduction in SBP, all-cause mortality, MI, CHF

Drug/Procedures Used:

Step 1: chlorthalidone 12.5 mg/day, dose 2 25 mg/day; Step 2: atenolol 25 mg/day, then 50 mg/day. Goal blood pressure was <160 mmHg for those with initial SBP>180 mmHg, and at least 20 mmHg for those with initial SBP 160-179 mmHg. At 5 years, 44% of placebo group was on antihypertensive therapy.

Principal Findings:

Target blood pressure (see above) was achieved by 65-72% in drug therapy group and 32-40% in placebo group. At 4.5 years, the drug therapy group had 36% fewer strokes (5.2 vs. 8.2/1,000; p = 0.0003), lower SBP (143 vs. 155 mm Hg), and a 27% reduction in nonfatal MI and coronary death. All-cause mortality was 9.0% in drug group and 10.2% in placebo group (RR 0.87, 95% CI 0.73-1.05). A subsequent report revealed a nearly 50% reduction in the occurrence of fatal or nonfatal heart failure in the drug therapy group (RR 0.51, 95% CI 0.37-0.71, p<0.001. Another report revealed that the LV mass index declined 13% with drug therapy versus a 6% increase in placebom group (p=0.01).


Drug therapy for isolated sytolic hypertension in patients aged 60 or greater was associated with a lower incidence of stroke and major cardiovascular events.


JAMA 1991; 265:3255–3264. Primary report. JAMA 1997; 278:212-6. Heart failure. JAMA 1998; 279: 778-80. LV mass.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Statins, Acute Heart Failure, Hypertension

Keywords: Drug Combinations, Stroke, Chlorthalidone, Diuretics, Heart Failure, Hypertension

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