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Executive Summary

LOW-DOSE DIURETICS REDUCE RISK OF STROKE BY 36% in elderly patients suffering from isolated systolic hypertension (ISH), according to a five-year, 5,000-patient study conducted by the National Heart, Lung and Blood Institute and reported in the June 25 Journal of the American Medical Association. ISH patients in the study receiving low doses of the diuretic chlorthalidone exhibited a "significant 36% reduction in the incidence of fatal and non-fatal strokes; a 27% reduction in the incidence of coronary heart disease; and a 32% reduction in the incidence of all cardiovascular episodes" when compared to placebo, NHLBI SHEP- Project Officer Jeffrey Probstfield, MD, reported. Patients in the active arm of the SHEP (Systolic Hypertension in the Elderly Program) study were treated with 12.5 mg chlorthalidone once a day. If they failed to experience a 20 mm drop in blood pressure with the diuretic alone, the active arm patients were given an enhanced regimen of chlorthalidone plus 25 mg of the beta-blocker atenolol (Stuart's Tenoretic). No "clinically important" side-effects or adverse events were associated with the low-dose pharmacotherapy, Probstfield said. At the end of the five-year trial, "non-fatal cardiovascular events were consistently lower for active treatment than placebo," the study found. There were 104 strokes and 140 episodes of coronary heart disease recorded among the 2,365 patients receiving chlorthalidone or chlorthalidone plus atenolol compared to 159 strokes and 189 CHD events among the 2,371 patients on placebo. Although the study employed a specific generic diuretic and beta blocker, the reduction in risks for stroke and coronary disease can be generalized to other products in the same categories. NIH researchers at a press conference announcing the study results commented that "any diuretic or diuretic/beta- blocker combination . . . with the same mechanisms of action" should produce similar clinical results. The SHEP study was the first to test the efficacy of antihypertensive drug treatment in reducing the risk of total stroke (nonfatal or fatal) for a multi-ethnic cohort of persons over 60 years of age with ISH. Elevated systolic blood pressure was until recently considered a natural part of the aging process and no treatment has been recommended for the approximately 3 mil. elderly Americans suffering from the condition. Based on the actuarial analysis of the SHEP results, NIH believes that more than 24,000 strokes and 50,000 cardiovascular episodes could be averted each year if all ISH patients were placed on low-dose pharmacotherapy. NHLBI has begun plans to publicize the results of the study with the aid of the National High Blood Pressure Council Education Coordinating Committee. The committee, comprising members of the nation's largest physician associations (including the AMA, the AHA, and the American College of Cardiologists) is scheduled to mail materials to its 37 member associations sometime "in the next two weeks," Probstfield reported. The materials, a four-page "abstract" explaining the study results and a list of references concerning the study, will then be mailed by each association to its member physicians. NHLBI also has prepared a three-page letter on the study to be distributed to any ISH patient who calls with questions. No company currently markets a 12.5 mg chlorthalidone although Stuart conceivably could take the lead in bringing a low-dose diuretic on line for the treatment of ISH. Lederle, however, may have an edge. The company's Probeta, a combination of the beta- blocker bisoprosol with a 6.5 mg dose of the diuretic hydrochlorothiazide, was recommended for approval by FDA's Cardio- Renal Advisory Committee in June ("The Pink Sheet" June 10, p. 5). Once the appropriate dose of chlorthalidone becomes available, the SHEP trial results could have a "profound" effect on public health costs, an editorial accompanying the JAMA report on the SHEP study suggests. The author, National Institute of Aging Director T. Franklin Williams, MD, noted that the cost of treating an ISH patient with diuretics should range from 10-25 cents per day and projected that potential savings to the public health care system arising from a reduction in strokes and cardiovascular episodes could be as great as $ 500 million a year.

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