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Doxazosin Treatment for Hypertension Associated with Increased Risk of Heart Failure in Diabetic Adults

Doxazosin as an antihypertensive therapy for adults with diabetes may be associated with an increased risk for heart failure, according to a recent report.

Alpha-blockers are known to produce a number of beneficial effects, including enhanced insulin sensitivity, inhibition of vasoconstriction, a favourable effect on lipid levels, and no adverse effect on renal function. Because of the multiple benefits, it has been suggested that alpha-blockers may a useful treatment for hypertension in patients with diabetes mellitus. However, little information is available on the cardiovascular outcomes for diabetes patients treated with these drugs.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was designed to compare the cardiovascular outcomes of patients treated with various categories of antihypertensive agents. In a recent report, Joshua Barzilay, MD, Division of Endocrinology, Kaiser Permanente of Georgia, Tucker, Georgia, United States, and colleagues compared the effects of doxazosin, an alpha-blocker, and chlorthalidone, a diuretic, on cardiovascular outcomes in ALLHAT participants over 55 years old with hypertension and glucose disorders.

The analysis included 8749 participants with known diabetes at study entry. Of these patients, 3220 were taking doxazosin and 5529 were taking chlorthalidone. Of the 13 877 participants without glucose disorders, 5235 were taking doxazosin and 8642 were taking chlorthalidone. In addition, the researchers analysed a post hoc subgroup of individuals with newly diagnosed diabetes (fasting glucose>125 mg/dL) or impaired fasting glucose (glucose 110-125 mg/dL) detected at trial entry, 606 of whom were taking doxazosin and 1084 who were taking chlorthalidone.

At 4-year follow up, the researchers detected a decrease in systolic and diastolic blood pressures from baseline for both treatments in both diabetic groups. Among participants with known diabetes, no difference was detected between treatments for coronary heart disease (CHD) or combined CHD outcomes, stroke, and all-cause mortality. However, the doxazosin group experienced an increase in combined cardiovascular disease (myocardial infarction, revascularisation procedures, angina, stroke, heart failure, and peripheral arterial disease) compared with the chlorthalidone group (relative risk [RR], 1.22; 95% confidence interval [CI], 1.11-1.33).

The difference in the diabetic group was largely due to heart failure incidence (RR, 1.85; 95% CI, 1.56-2.19; P < .001]. An increased incidence of heart failure was also detected in doxazosin-treated participants in the newly diagnosed glucose disorder group (RR, 1.63; 95% CI, 1.05-2.55; P =.03) and in the group without known glucose disorders (RR, 1.92; 95% CI, 1.62-2.28; P < .001).

Due to the increased incidence of heart failure, the researchers conclude that, "doxazosin should not be a first-line single agent choice for the treatment of hypertension in adults with glucose disorders."

J Clin Hypertens (Greenwich) 2004 Mar;6:3:116-25. "Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study"

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