Initial Antihypertensive Drug Therapy Final Report of a Randomized, Controlled Trial Comparing a-Blocker and Diuretic

We compared the effect on serum Upids of an α-blocker (prazosin) and a diuretic (hydrochlorothiazide) used as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry blood pressure, 148/97 mm Hg, with no major organ system damage). A two-center trial randomized patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not achieved with the originally assigned drug, and patients were removed from any drug they were not able to tolerate. After an average of 40 weeks on the assigned drug regimen, a decline was observed in prazosin-treated patients in both serum total cholesterol (−9.3 mg/dl) and serum triglycerides (−33.9 mg/dl). In contrast, an increase in both these Upids was seen in hydrochlorothiazide-treated patients (+5.0 mg/dl for serum total cholesterol and + 18.6 mg/dl for serum triglycerides). The net trial differences between the groups were 14.3 mg/dl for total cholesterol and 52.5 mg/dl for triglycerides, in favor of prazosin (p < 0.001 for both comparisons). These differences in Upids between the two groups persisted into the second year of the trial (p < 0.05). There were no significant differences between the drug groups in regard to the level of high density Upoprotein cholesterol or its subtractions or low density Upoprotein cholesterol. In patients who required a combination of the two drugs to achieve blood pressure control, the a-blocker diminished or eliminated the Upid-raising effects of the diuretic. Both drugs were similar in their ability to control the elevation of diastoUc pressure. More patients were unable to tolerate prazosin than were unable to tolerate hydrochlorothiazide. For those able to continue with prazosin, either as the single initial treatment or in combination with hydrochlorothiazide, the lipki response appeared to be an asset in regard to avoiding possible atherogenic effects of treatment and thereby possibly reducing coronary risk.