Single-Drug Therapy for Hypertension in Men -- A Comparison of Six Antihypertensive Agents with Placebo
Barry J. Materson, Domenic J. Reda, William C. Cushman, Barry M. Massie, Edward D. Freis, Mahendr S. Kochar, Robert J. Hamburger, Carol Fye, Raj Lakshman, John Gottdiener, Eli A. Ramirez, William G. Henderson, for The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents
Background Characteristics such as age and race are often citedas determinants of the response of blood pressure to specificantihypertensive agents, but this clinically important issuehas not been examined in sufficiently large trials, involvingall standard treatments, to determine the effect of such factors.
Methods In a randomized, double-blind study at 15 clinics, weassigned 1292 men with diastolic blood pressures of 95 to 109mm Hg, after a placebo washout period, to receive placebo orone of six drugs: hydrochlorothiazide (12.5 to 50 mg per day),atenolol (25 to 100 mg per day), captopril (25 to 100 mg perday), clonidine (0.2 to 0.6 mg per day), a sustained-releasepreparation of diltiazem (120 to 360 mg per day), or prazosin(4 to 20 mg per day). The drug doses were titrated to a goalof less than 90 mm Hg for maximal diastolic pressure, and thepatients continued to receive therapy for at least one year.
Results The mean (±SD) age of the randomized patientswas 59 ±10 years, and 48 percent were black. The averageblood pressure at base line was 152 ±14/99 ±3mm Hg. Diltiazem therapy had the highest rate of success: 59percent of the treated patients had reached the blood-pressuregoal at the end of the titration phase and had a diastolic bloodpressure of less than 95 mm Hg at one year. Atenolol was successfulby this definition in 51 percent of the patients, clonidinein 50 percent, hydrochlorothiazide in 46 percent, captoprilin 42 percent, and prazosin in 42 percent; all these agentswere superior to placebo (success rate, 25 percent). Diltiazemranked first for younger blacks (<60 years) and older blacks( 60 years), among whom the success rate was 64 percent, captoprilfor younger whites (success rate, 55 percent), and atenololfor older whites (68 percent). Drug intolerance was more frequentwith clonidine (14 percent) and prazosin (12 percent) than withthe other drugs.
Conclusions Among men, race and age have an important effecton the response to single-drug therapy for hypertension. Inaddition to cost and quality of life, these factors should beconsidered in the initial choice of a drug.
Source Information
From the Cooperative Studies Program of the Medical Research Service, Department of Veterans Affairs. Presented in part at the American Heart Association Scientific Sessions, Anaheim, Calif., November 11, 1991.The members of the study group are listed in the Appendix.
Address reprint requests to Dr. Materson at the Veterans Affairs Medical Center (141), 1201 NW 16th St., Miami, FL 33125.
Single-Drug Therapy for Hypertension in Men
Johnston G. D., Pettinger W. A., Lee H.-C., Paulshock B. Z., Materson B. J., Reda D. J., Cushman W. C., Rouse C. F.
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N Engl J Med 1993;
329:1043-1045, Sep 30, 1993.
Correspondence
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A correction has been published: N Engl J Med 1994;330(23):1689.
60 years), among whom the success rate was 64 percent, captopril for younger whites (success rate, 55 percent), and atenolol for older whites (68 percent). Drug intolerance was more frequent with clonidine (14 percent) and prazosin (12 percent) than with the other drugs. 
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