Don’t pick doxazosin for first-line therapy
Don’t pick doxazosin for first-line therapy
Physicians should carefully reassess the use of the alpha blocker drug doxazosin for the treatment of hypertension, say researchers. A large clinical trial has found patients taking the drug were twice as likely to be hospitalized for CHF as those taking a diuretic.
The trial’s sponsor, the Bethesda, MD-based National Heart, Lung and Blood Institute, halted the doxazosin arm in March after investigators announced that the approximately 9,000 study participants who took doxazosin had 25% more serious complications from hypertension than the group taking the diuretic chlorthalidone.
The risk of developing CHF was 1% per year in the diuretic group and doubled to 2% per year for those in the doxazosin group, says Curt Furberg, MD, PhD, chairman of the study’s steering committee from Wake Forest University Baptist Medical Center in Winston-Salem, NC.
The study, known as ALLHAT (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) is the largest ever to compare the efficacy of newer drugs against the standby diuretics for the treatment of hypertension. More than 42,000 high-risk antihypertensive patients at 623 clinical sites in the United States, Puerto Rico, the Virgin Islands, and Canada are participating to see if the drugs reduce the incidence of coronary artery disease.
In addition to doxazosin (Cardura, Pfizer Inc., New York City), ALLHAT is also looking at the calcium antagonist amlodipine (Norvasc, Pfizer) and the ACE inhibitor lisinopril (Prini-vil, Merck & Co., Whitehouse Station, NJ, and Zestril, AstraZeneca Pharmaceuticals, Wilming-ton, DE). Only the doxazosin portion of the study will stop.
A total of about 900 patients developed heart failure during the study, Furberg says. "It’s not clear why there was an increased risk of heart failure. This was a surprise finding. Right now, one can only speculate."
After the researchers presented their findings1 at the American College of Cardiology’s 49th Annual Scientific Session in March in Anaheim, CA, the organization issued a clinical alert on alpha blockers for hypertension that urged physicians to reassess their use of doxazosin.
"The diuretic remains the drug of choice because it’s effective, safe, and cheap," he says. "ALLHAT is a test to see how newer, much more expensive drugs compare to standard treatment with diuretics. One drug lost, and on the other two, we’ll have to see. Until we have that information, the diuretic is the drug of choice."
Furberg says that Cardura was shown to be inferior overall to chlorthalidone, a cheaper drug, for hypertension control, drug compliance, and reduction of cardiovascular complications. Cardura should be at the bottom of the list of drugs from which physicians choose to treat hypertension, he says. It should not be considered as first-line therapy for hypertension.
"Heart failure is the most common reason for hospitalization of older people, and it’s the most costly. This is serious. You don’t want to double the risk and pay 10 times more for it," he adds.
The drugs in the study were similarly effective in preventing heart attacks and in reducing the risk of death from all causes; the heart failure outcome was the only major difference.
"The assumption has been, for quite a while, that the entire benefit of blood pressure lowering drugs is lowering blood pressure, but that is not the case anymore," Furberg says. "We have more and more data showing that drugs have other effects. There must be some other mechanism at work because of the difference in heart failure. We are beginning to understand more and more that we can’t look at blood pressure reduction and say we know all the clinical effects. It varies with the drugs."
Patients in the doxazosin group had slightly higher systolic blood pressures than the chlor-thalidone group, although the diastolic pressures were the same. The doxazosin group also had poorer compliance with treatment. Only 75% were still on the drug or another alpha blocker after four years, compared with 86% still taking chlorthalidone or another diuretic.
Reference
1. Davis BR, et al. Major cardiovascular events in hypertensive patients randomized to doxazosin vs. chlorthalidone: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2000; 283:1,967-1,975.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.