RESPONSE TO A 2ND SINGLE ANTIHYPERTENSIVE AGENT USED AS MONOTHERAPY FOR HYPERTENSION AFTER FAILURE OF THE INITIAL-DRUG

Background: An important issue in clinical practice is how to treat pa tients whose blood pressure does not respond to the first antihyperten sive drug selected. Objective: To analyze the antihypertensive respons e of patients who had failed to achieve their diastolic blood pressure goal (< 90 mm Hg at the end of 8 to 12 weeks of titration) with one,o f six randomly allocated drugs or placebo to the random allocation of an alternate drug. Methods: We initially randomized 1292 men with dias tolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorot hiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydro chloride (sustained release), prazosin hydrochloride, or placebo. Of 4 10 men in whom initial treatment failed, 352 qualified for randomizati on to the alternate drug. Results: Of the 352 patients, 173 (49.1%) ac hieved their goal diastolic blood pressure, in 133 (37.8%) the alterna te drug failed, and 46 (13.1%) left the study for various reasons. Ove rall response rates were as follows: diltiazem, 63%; clonidine, 59%; p razosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%, and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide f ailed was achieved with diltiazem (70%); after atenolol failure, cloni dine (86%);after captopril failure, prazosin (54%); after clonidine fa ilure, diltiazem (100%), after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate f or patients initially randomized to an active treatment was 76.0%, whi ch is similar to that achieved by the combination of two drugs in prev ious studies. Conclusions: We conclude that sequential single-drug the rapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.