Isolated systolic hypertension frequently precedes heart failure. The Systolic Hypertension in the Elderly Program (SHEP) showed that low-dose chlorthalidone significantly reduced the incidence of stroke and major cardiovascular events. Kostis and colleagues, for the SHEP Cooperative Research Group, evaluated the effect of diuretics on the occurrence of heart failure in study patients with isolated systolic hypertension.

Patients were randomized to receive either placebo or 12.5 mg per day of chlorthalidone. If this dosage did not satisfactorily control blood pressure within two months, it was increased to 25 mg per day. If this, too, failed to lower blood pressure, atenolol in a dosage of 25 mg per day or matching placebo was added. A final increase to 50 mg of atenolol daily or matching placebo was allowed, if needed. Patients began open-label treatment if the stepped-care protocol did not control their hypertension. Heart failure was diagnosed if patients had dyspnea at rest, orthopnea or paroxysmal nocturnal dyspnea, or were in New York Heart classification III. Also, one or more of the following signs was required: rales, 2+ ankle edema, tachycardia of greater than 120 beats per minute, radiographic evidence of cardiomegaly or congestive heart failure, S3 gallop or distention of the jugular vein.

A total of 2,365 patients were randomized to receive active treatment, and 2,371 received placebo. At baseline, only 0.3 percent of the patients had a history of heart failure. Five years after baseline, 90 percent of the patients were receiving some form of antihypertensive therapy. Heart failure (both fatal and nonfatal) was less prevalent in the treatment group than in the placebo group. During an average of 4.5 years of follow-up, fatal and nonfatal heart failure occurred in 55 of the 2,365 patients receiving therapy and in 105 of the 2,371 patients receiving placebo (relative risk: 0.51). The risk of heart failure was greater in those with higher systolic blood pressures at baseline and in those who were older. Patients receiving active therapy in each higher-risk group had a lower rate of heart failure than patients in the placebo group with these risk factors. The addition of atenolol was not found to provide any additional protection from heart failure compared with chlorthalidone alone.

The authors conclude that diuretic-based stepped-care treatment of isolated systolic hypertension in the elderly is protective against the development of heart failure in this population. The reduction in risk of heart failure is approximately 50 percent and, in patients with a history of myocardial infarction, the reduction may range up to 80 percent.