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John B. Kostis, MD; Barry R. Davis, MD, PhD; Jeffrey Cutler, MD; Richard H. Grimm, Jr, MD, PhD; Kenneth G. Berge, MD; Jerome D. Cohen, MD; Clifton R. Lacy, MD; H. Mitchell Perry, Jr, MD; M. Donald Blaufox, MD, PhD; Sylvia Wassertheil-Smoller, PhD; Henry R, Black, MD; Eleanor Schron, RN, MS; David M. Berkson, MD; J. David Curb, MD; W. McFate Smith, MD; Robert McDonald, MD; William B. Applegate, MD

JAMA. 1997;278(3):212-216.

Abstract
Context.
—Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known.

Objective.
—To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension.

Design.
—Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Participants.
—A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP).

Intervention.
—Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo.

Main Outcome Measures.
—Fatal and nonfatal heart failure.

Results.
—During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71; P<.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53; P=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure.

Conclusion.
—In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.

Author Affiliations
for the SHEP Cooperative Research Group

From the Department of Medicine, Center for Disease Management and Clinical Outcomes, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (Drs Kostis and Lacy); University of Texas Health Science Center atHouston (Dr Davis); National Heart, Lung, and Blood Institute, Bethesda. Md (Dr Cutler and Ms Schron); Minneapolis Medical Research Foundation, Shapiro Center for Evidence-Based Medicine, and the University of Minnesota, Minneapolis (Dr Grimm); Department of Community Internal Medicine. Mayo Medical School, Rochester, Minn (Dr Berge); Department of Internal Medicine, Washington University School of Medicine, St Louis, Mo (Drs Cohen and Perry); Departments of Nuclear Medicine and Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY (Drs Blaufox and Wassertheil-Smoller); Department of Preventive Medicine, Rush-Presbyterian-St Luke's; Medical Center, Chicago, Ill (Dr Black); Department of Medicine, Northwestern University Medical School, and the Ida and Norman Stone Medical Center, Chicago, Ill (Dr Berkson); Department of Medicine, John A. Burns School of Medicine, and the Pacific Health Research Institute, Honolulu. Hawaii (Dr Curb); Health Sciences Division, SRI International, Menlo Park, Calif (Dr Smith); Department of Medicine, University of Pittsburgh School of Medicine. Pittsburgh. Pa (Dr Mc-Donald); and the Department of Preventive Medicine, University of Tennessee, Memphis (Dr Applegate).

Footnotes
A complete listing of the members of the SHEP Cooperative Research Group appears at the end of the following article: JAMA. 1991;265:3255-3264.

Reprints: John B. Kostis, MD, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson PI, CN19, New Brunswick, NJ 08903-0019 (e-mail: kostis@umdnj.edu).

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