Evaluation of drug treatment in mild hypertension: VA-NHLBI feasibility trial. Plan and preliminary results of a two-year feasibility trial for a multicenter intervention study to evaluate the benefits versus the disadvantages of treating mild hypertension. Prepared for the Veterans Administration-National Heart, Lung, and Blood Institute Study Group for Evaluating Treatment in Mild Hypertension.
A feasibility trial to investigate the practicality of determining the advantages and disadvantages of prompt pharmacologic treatment for mild hypertension was jointly funded by the Veterans Administration and the National Heart, Lung and Blood Institute. Its clinical phase has been completed, and it demonstrated 1. that the required relatively young asymptomatic population could be enrolled in the study and 2. that it could be persuaded to adhere to the protocol for 2 years; however, it was evident that intensive efforts would be required in both areas. The feasibility trial screened almost 120,000 potential subjects over a period of 16 months to randomize about 1,000 subjects at four clinical centers. These men and women were 21 to 50 years old, had diastolic pressures from 85 to 105 mm Hg as outpatients, and had no evidence of cardiovascular renal abnormalities. They were randomized in double-blind fashion into active drug therapy and placebo groups. Stepped care therapy involved 50 mg chlorthalidone (Step 1), 100 mg chlorthalidone (Step 2) and 100 chlorthalidone plus 0.25 mg reserpine (Step 3). Death, myocardial infarction, stroke, angina pectoris, and congestive heart failure were the "major" morbid events that were looked for; also recorded were "minor" morbid events consisting primarily of electrocardiographic arrhythmias. The development of significant hypertension was considered a treatment failure. Side effects were carefully tabulated in both active drug and placebo groups. The study revealed an average drop in diastolic pressure of almost 12 mm Hg for active drug group and less than half of that for the placebo group; once established 6 months after randomization, the new pressure levels persisted almost without change throughout the study. Although the feasibility trial was not designed to answer the primary question regarding the benefits of treatment, the events were tabulated for each group. A total of 12 placebo-treated subjects developed significant hypertension and were put on active drug. There was not a significant difference between the two groups in the incidence of "major" morbid events; a total of eight active and five placebo patients developed myocardial infarction or died suddenly. There, however, was an excess of arrhythmias among the active drug subjects (17 in the active group versus 8 in the placebo group on the basis of preliminary data). Finally, there were twice as many side effects and 20 times as many chemical abnormalities among the active as among the placebo subjects. A protocol for a full scale study of the benefits of pharmacologic therapy in mild hypertensives has been prepared and is ready for implementation as needed; it involves relatively minor modifications of the protocol tested in the feasibility trial.