Systolic Hypertension in the Elderly Program

Black DM, Brand RI, Greenlick M, et al Compliance to treatment for hypertension in elderly patients The SHEP pilot study. Systolic Hypertension in the Elderly Program. J Gerontol 1987 42 552-557. 

The issues of whether hyperuricemia is an independent risk factor for cardiovascular disease and the clinical relevance of the rise in serum uric acid caused by diuretic treatment are controversial (SED-14, 660 351). In the Systolic Hypertension in the Elderly Program (SHEP), diuretic-based treatment in 4327 men and women, aged 60 years or more, with isolated systolic hypertension was associated with significant reduction in cardiovascular events (SED-14, 657). Serum uric acid independently... 

SHEP Cooperative Research Gronp. Prevention of stroke by antihypertensive drng treatment in older persons with isolated systolic hypertension. Final resnlts of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991 265(24) 3255-64. 

A series of trials in elderly hypertensive subjects has shown a very pronounced reduction in cardiac events as a result of treatment based on thiazide diuretics. In the European Working Party on Hypertension in the Elderly (EWPHE) trial (13), total cardiovascular deaths were reduced by 38%, all cardiac deaths by 43%, and deaths due to myocardial infarction by 60%. Benefits in the Systolic Hypertension in the Elderly Program (SHEP) included a reduction in fatal and non-fatal myocardial infarction of 25% and major cardiovascular events of 32% (14) and were seen in those with and without electrocardiographic abnormalities at entry. The risk of heart failure was also reduced in patients taking chlortalidone-based therapy (15). Relative risk was similar in patients with and without non-insulin dependent diabetes meUitus absolute risk reduction was twice as great in the diabetic subjects (16). The Swedish Trial of Old Patients with Hypertension (STOP-Hypertension) reported a significant reduction in myocardial infarction and all-cause mortahty (17). In the MRC Trial in elderly adults (18), diuretic treatment reduced coronary events by 44% and fatal cardiovascular events by 35%. 

Curb JD, Pressel SL, Cutler JA, Savage PJ, Applegate WB, Black H, Camel G, Davis BR, Frost PH, Gonzalez N, Guthrie G, Oberman A, Rutan GH, Stamler J. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA 1996 276(23) 1886-92. 

Three landmark placebo-controlled clinical trials have established the benefits of both hypertension treatment and diuretic therapy. The Systolic Hypertension in the Elderly Program (SHEP), the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension), and the Medical Research Council (MRC) trial " showed significant reductions in stroke, myocardial infarction, and aU-cause cardiovascular disease and mortality with thiazide diuretic-based therapy versus placebo. These trials allowed for /3-blockers as add-on therapy for BP control. Newer agents (i.e., ACE inhibitors, angiotensin II receptor blockers [ARBs], and calcium channel blockers [CCBs]) were not available at the time of these studies. However, subsequent clinical trials have compared these newer antihypertensive agents (ACE inhibitors, ARBs, and CCBs) to diuretics." These data show similar effects, but most trials used a prospective, open-label, blinded end point (PROBE) study methodology that is... 

The Systolic Hypertension in the Elderly Program (SHEP) Cooperative Research Group (1988) Rationale and design of a randomized clinical trial on prevention of stroke in isolated systolic hypertension. J Clin Epidemiol 41 1197-1208... 

---