Lessons from combination therapy in Veterans Affairs Studies. Department of Veterans Affairs Cooperative Study Group on antihypertensive agents.

A subset of 102 patients of an original cohort of 1292 with stage 1 to 2 hypertension was characterized by having failed to achieve goal blood pressure (< 90 mm Hg diastolic) after treatment with two single antihypertensive drugs. These patients were given a combination of the two drugs on which they had failed to achieve blood pressure goal when they were administered as single-drug therapy. The drugs were hydrochlorothiazide, atenolol, captopril, diltiazem-SR, clonidine, and prazosin. We examined the responses in each of the drug combination categories by the order that the drugs were administered, by estimated total response rates for the combinations, and by age and race. The order of drug administration did have an effect for some of the drug pairs. This was of two types: 1) different results for each member of the pair, but the same combination result; and 2) different end result of the combination. An example of the first type is that prazosin had only a 6% response rate in patients who had failed on diltiazem, while diltiazem had a 22% response rate in patients who had failed on prazosin. Nevertheless, the combinations yielded the same total responses (86% and 84%) regardless of order. An example of the second type is that captopril-diltiazem was less effective in total response than diltiazem-captopril (88% v 97%). Differences were seen in the response to combinations in the race and age groups. There were ordering differences of type similar to those described above. We conclude that combination drug therapy is highly effective even when the individual components have failed and that some differences in response by order of drug administration may occur.