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December 18, 1996

Effect of Diuretic-Based Antihypertensive Treatment on Cardiovascular Disease Risk in Older Diabetic Patients With Isolated Systolic Hypertension

Author Affiliations

for the Systolic Hypertension in the Elderly Program Cooperative Research Group
From the John A. Burns School of Medicine, Honolulu, Hawaii (Dr Curb); the University of Texas School of Public Health, Houston (Ms Pressel and Dr Davis); the National Heart, Lung, and Blood Institute, Bethesda, Md (Drs Cutler and Savage); University of Tennessee, Memphis (Dr Applegate); Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill (Dr Black); Washington University School of Medicine, St Louis, Mo (Dr Camel); University of California, San Francisco (Dr Frost); University of Minnesota, Minneapolis (Dr Gonzalez); University of Kentucky, Lexington (Dr Guthrie); University of Alabama at Birmingham (Dr Oberman); Veterans Affairs Medical Center, Memphis, Tenn (Dr Rutan); and Northwestern University, Chicago, Ill (Dr Stamler).

JAMA. 1996;276(23):1886-1892. doi:10.1001/jama.1996.03540230036032

Objective.  —To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulintreated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients.

Design.  —Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP).

Setting.  —Multiple clinical and support centers in the United States.

Paticipants.  —a total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], ≥160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (≥140 mg/dL), or any combination of these characteristics.

Intervention.  —The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patient's private physician for persistently high BP.

Main Outcome Measures.  —The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality.

Results.  —The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group. Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients.

Conclusion.  —Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic older patients with ISH.