The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was conducted to determine whether chlorthalidone or three other antihypertensives had differing effects on fatal coronary heart disease (CHD) and nonfatal myocardial infarction (MI).

ALLHAT included patients who were at least 55 years of age and had a systolic blood pressure of at least 140 mm Hg and/or a diastolic blood pressure of at least 90 mm Hg (or were taking antihypertensive medication), and had one other CHD risk factor. Patients were randomly assigned to receive doxazosin, chlorthalidone, lisinopril or amlodipine. The treatment goal was a blood pressure reading less than 140/90 mm Hg using the lowest possible dosage of the assigned study drug. If the maximal tolerated dosage of the assigned medication did not achieve the desired blood pressure level, therapy with an open-label agent (atenolol, reserpine, clonidine or hydralazine) was started. Patients were seen every three months for the first year and every four months after that. Fatal CHD and non-fatal MI were the primary end points. This current report compares the doxazosin group to the chlorthalidone group.

There were 15,268 patients in the chlorthalidone group and 9,067 in the doxazosin group. Initial blood pressure levels were similar in both groups. At two years, 61 percent of patients in the chlorthalidone group and 54 percent in the doxazosin group achieved the blood pressure goal. After four years, the proportions increased to 64 and 58 percent, respectively. There was no significant difference in fatal CHD or all-cause mortality between the two groups. The comparison study was terminated early because patients in the doxazosin group had a 25 percent higher incidence of major cardiovascular disease events than patients in the chlorthalidone group. The relative risks of combined CHD and stroke were 1.10 and 1.19, respectively, in the doxazosin group versus the chlorthalidone group. The relative risk of congestive heart failure was 2.04 in the doxazosin group, and this group also had a higher risk of needing coronary revascularization and of angina than patients in the chlorthalidone group.

The ALLHAT Officers conclude that doxazosin is less effective than chlorthalidone as a first-line antihypertensive agent. This finding comes in spite of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure's recommendation to consider alpha blockers such as doxazosin as first-line treatment for hypertension. Doxazosin may be useful as part of an antihypertensive regimen, and further studies are needed to determine if it is more effective than placebo. In an accompanying editorial, Lasagna points out that although doxazosin has many potential advantages (such as its beneficial effect on lipids), it cannot currently be recommended as first-line treatment for hypertension based on the ALLHAT results.