• J D Curb, S L Pressel, J A Cutler, P J Savage, W B Applegate, H Black, G Camel, B R Davis, P H Frost, N Gonzalez, G Guthrie, A Oberman, G H Rutan, and J Stamler.
• John A. Burns School of Medicine, Honolulu, Hawaii, USA.
• JAMA. 1996 Dec 18;276(23):1886-92.

ObjectiveTo assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients.DesignDouble-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP).SettingMultiple clinical and support centers in the United States.ParticipantsA total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 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 (> or = 140 mg/dL), or any combination of these characteristics.InterventionThe 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 MeasuresThe 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.ResultsThe 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.ConclusionLow-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.

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