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Should alpha-blockers ever be used as antihypertensive drugs?

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Alpha-blockers should not be used as first-line therapy for hypertension. However, an alpha-blocker can be considered as a second-line or third-line add-on in a patient whose blood pressure is not under control despite treatment with other drugs.

In addition, alpha-blockers are useful in relieving lower urinary tract symptoms in patients with benign prostatic hypertrophy. However, even in a patient who has both hypertension and benign prostatic hypertrophy, we advise physicians to use alpha-blockers primarily to relieve the urinary symptoms, and we recommend lowering the blood pressure with a drug of a class shown to reduce rates of illness and death.

NOT FIRST-LINE THERAPY

All antihypertensive drugs, including alpha-blockers, lower blood pressure. Alpha-blockers have been approved by the US Food and Drug Administration for treating high blood pressure, and they are just as effective as other antihypertensive drugs—if efficacy is defined as a decrease in millimeters of mercury.

However, lowering the blood pressure is not the main goal of antihypertensive therapy. What we want to achieve when prescribing antihypertensive drugs is to reduce the rates of heart attacks, strokes, and other adverse cardiovascular adverse outcomes, including death.

Unfortunately, alpha-blockers fall short in this regard. In the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack (ALLHAT) trial,1,2 doxazosin (Cardura) was found to carry a higher risk of combined cardiovascular disease (relative risk 1.19, P = .04), mostly stroke. Alarmingly, the incidence of symptomatic heart failure in patients on doxazosin was twice that in patients on chlorthalidone (relative risk 2.04, P < .001). Doxazosin was minimally more effective in lowering blood pressure than chlorthalidone, but the small difference in blood pressure was unlikely to have accounted for the significant difference in the risk of heart failure.3

This experience with doxazosin illustrates a key drawback to surrogate end points: a treatment may produce a favorable outcome in the surrogate end point (blood pressure) but produce little or no benefit in terms of the real end point (stroke, myocardial infarction, and heart failure).4

Based on the ALLHAT data as well as on a Veterans Administration study in patients with chronic heart failure in which survival with prazosin (Minipress) was no better than with placebo,5 it seems reasonable to no longer use alpha-blockers as initial therapy for hypertension. This view is reflected by current European6 and American7 guidelines.

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