September 11, 1995

Response to a Second Single Antihypertensive Agent Used as Monotherapy for Hypertension After Failure of the Initial Drug

Author Affiliations

Miami, Fla; Hines, Ill; Albuquerque, NM; Washington, DC; Boston, Mass; Allen Park, Mich; Dallas, Tex; East Orange, NJ; Houston, Tex; Jackson, Miss; Manhattan, NY; Memphis, Tenn; Milwaukee, Wis; St Louis, Mo; San Francisco, Calif; Topeka, Kan; Data Monitoring Board; University of Texas Medical School, Houston; Worcester (Mass) Memorial Hospital; Cleveland (Ohio) Clinic Foundation; University of Iowa College of Medicine, Iowa City. Veterans Affairs Central Office; Boston and Washington

From the Cooperative Studies Program, Medical Research Service, Department of Veterans Affairs, Washington, DC. Members of the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents are listed in a box on page 1762.

Arch Intern Med. 1995;155(16):1757-1762. doi:10.1001/archinte.1995.00430160089009

Background:  An important issue in clinical practice is how to treat patients whose blood pressure does not respond to the first antihypertensive drug selected.

Objective:  To analyze the antihypertensive response 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 of six randomly allocated drugs or placebo to the random allocation of an alternate drug.

Methods:  We initially randomized 1292 men with diastolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorothiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydrochloride (sustained release), prazosin hydrochloride, or placebo. Of 410 men in whom initial treatment failed, 352 qualified for randomization to the alternate drug.

Results:  Of the 352 patients, 173 (49.1%) achieved their goal diastolic blood pressure, in 133 (37.8%) the alternate drug failed, and 46 (13.1%) left the study for various reasons. Overall response rates were as follows: diltiazem, 63%; clonidine, 59%; prazosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%; and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide failed was achieved with diltiazem (70%); after atenolol failure, clonidine (86%); after captopril failure, prazosin (54%); after clonidine failure, diltiazem (100%); after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate for patients initially randomized to an active treatment was 76.0%, which is similar to that achieved by the combination of two drugs in previous studies.

Conclusions:  We conclude that sequential single-drug therapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.(Arch Intern Med. 1995;155:1757-1762)