Effects of antihypertensive therapy on blood pressure control, cognition, and reactivity. A placebo-controlled comparison of prazosin, propranolol, and hydrochlorothiazide.

A randomized, placebo-controlled trial was conducted to compare the effects of treatment with prazosin, propranolol, or hydrochlorothiazide on the following variables: blood pressure, cognitive and psychomotor skills, cardiovascular reactivity to natural and laboratory challenges, and serum lipid and lipoprotein levels. Side effects were recorded and patients evaluated how they felt during their treatment. Sixty-nine men, 35 percent black, aged 25 to 55 (mean 51.3) years, with diastolic blood pressures between 90 and 104 mm Hg (mean, 93.3 mm Hg), completed the study. There were no differences between active treatment groups in the proportion of patients with controlled blood pressure during the maintenance phase of the study. In the cognitive and psychomotor tests, the hydrochlorothiazide group showed significantly less improvement from baseline than the other treatment groups on the block design subscale of the Wechsler Adult Intelligence Scale-Revised, and there was a trend for the propranolol group to have less improvement from baseline than the other groups on the digit span subscale. There were no other significant pretreatment to post-treatment changes in the other cognitive or psychomotor tests, the Russell Revision of the Wechsler Memory Scale, or a number of computerized reaction-time and signal-detection tasks. In the reactivity testing, there was a significantly lower increase in heart rate in the prazosin group compared with placebo during the second laboratory challenge of the Stroop Color Interference Test. Post-treatment declines in ambulatory blood pressure were seen in all of the drug treatment groups in average and maximal diastolic and systolic blood pressures. Both propranolol and hydrochlorothiazide treatment resulted in low-density lipoprotein cholesterol levels that were higher than baseline and the hydrochlorothiazide treatment had significantly increased total cholesterol levels. In contrast, the prazosin-treated group experienced no adverse changes in these parameters. Overall, the propranolol group had significantly more moderate and severe side effects than did the other three groups. Considering the pattern of blood pressure control, cognitive and psychomotor effects, changes in lipid levels, and magnitude of side effects, prazosin seems to have the most advantageous profile in this study of the three anti-hypertensive agents evaluated.