Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension

J. David Curb, Sara L. Pressel*, Jeffrey A. Cutler, Peter J. Savage, William B. Applegate, Henry Black, Greta Camel, Barry R. Davis, Phillip H. Frost, Nelly Gonzalez, Gordon Guthrie, Albert Oberman, Gail H. Rutan, Jeremiah Stamler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

865 Scopus citations

Abstract

Objective. - To 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. 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. Participants. - 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 non-diabetic 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.

Original languageEnglish (US)
Pages (from-to)1886-1892
Number of pages7
JournalJournal of the American Medical Association
Volume276
Issue number23
DOIs
StatePublished - Dec 18 1996

ASJC Scopus subject areas

  • Medicine(all)

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