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For Hypertension, Cheaper May Be Better

A huge, long-awaited federal study of patients suffering from hypertension proved what many experts have long suggested -- that inexpensive diuretics are much better than far more popular, and costly, medicines for lowering blood pressure and preventing heart disease. The $120 million study, reported in the Dec. 18 issue of the Journal of the American Medical Association, followed 42,418 patients aged 55 and older for eight years. It's by far the largest and longest head-to-head study comparing different hypertension drugs.

The results, if acted on, could make a big difference in the nation's health bill. About 24 million Americans take drugs to lower high blood pressure, at an estimated annual cost of $15.5 billion. But most of those dollars go to prescriptions for ACE inhibitors and calcium-channel blockers (see table), drugs introduced in the '80s that can cost 10 times to 15 times as much as the 50-year-old diuretics, which are essentially water pills. Recent studies have found that diuretics make up less than 11% of the total prescriptions for hypertension, despite being recommended by federal guidelines as a first line of treatment for the disease and costing only about $3 a month.

The Antihypertensive & Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study was conducted at 623 clinics across the U.S., Canada, Puerto Rico, and the U.S. Virgin Islands. Participants had high blood pressure and at least one other risk factor for heart disease, such as smoking or type-2 diabetes. The patients were randomly assigned to one of four drugs: a diuretic, a calcium-channel blocker, an ACE inhibitor, or an alpha-adrenergic blocker. The alpha-adrenergic blocker arm was stopped in March, 2000, however, because those patients were twice as likely to be hospitalized for heart failure as users of the diuretic.

MONEY VS. MEDICINE. For the remaining patients, the study found that after five years of follow-up, patients taking calcium-channel blockers, when compared with those on diuretics, had higher blood-pressure readings, a 38% higher risk of developing heart failure, and a 35% higher risk of being hospitalized for the condition. Those on ACE inhibitors, compared with diuretics, also had higher blood pressure readings, as well a 15% higher risk of stroke (40% higher for African Americans), 19% higher risk of heart failure, 11% greater risk of being hospitalized, and a 10% greater risk of having to undergo bypass surgery.

"ALLHAT shows that diuretics are the best choice to treat hypertension and reduce the risk of complications, both medically and economically," says Claude Enfant, director of the National Heart, Lung, & Blood Institute (NHLBI), which sponsored the study.

Advocates, however, will be fighting a battle against well-heeled drug companies that make a lot more money from brand-name ACE inhibitors and calcium-channel blockers than generic diuretics. A 1998 study by researchers from Massachusetts General Hospital in Boston found that calcium-channel blockers were the most heavily advertised of any drug in the New England Journal of Medicine, while it was difficult to find a single ad for diuretics.

SPREADING THE WORD. The study's investigators say they're now determined to get the message out that diuretics should be the first line of treatment against hypertension. The information is desperately needed: Hypertension afflicts more than 50 million Americans, 1 in every 4 adults, but only 25% of its victims have their blood pressure adequately controlled. If left untreated, hyptension sharply increases the risk of heart disease and stroke, because the higher the pressure of blood against the walls of the arteries, the harder the heart has to work.

Dr. Paul Whelton, senior vice-president for health sciences at Tulane University in New Orleans and a regional coordinator for ALLHAT, says the study should end any questions about the usefulness of diuretics. It's the first to show that "it really does matter how you lower blood pressure, not just that you lower it," he says. Although earlier studies found that the newer drugs were effective when judged against placebos, they were never tested directly against diuretics. "Our next issue is to get this information out and get it into practice," he says. To that end, the NHLBI has formed a dissemination committee to work with doctors, insurers, and pharmacies to spread the word.

Drug companies are sure to counter the ALLHAT study by pointing out that diruetics often have to be taken three times a day, compared with once a day for the newer drugs, which can be a big issue for a disease whose victims are frequently noncompliant with treatment. Diuretics can also cause frequent urination, which can be unpleasant. Still, Whelton says, "diuretics are very, very well tolerated. For the vast majority of patients a diuretic makes sense as a first line of treatment."


Drugs that lower blood pressure

DIURETICS Also called water pills, they flush excess water and salt from the body. Excess water and salt can cause blood pressure to rise.

ACE INHIBITORS The most commonly prescribed hypertension drugs, they block the formation of a hormone that narrows blood vessels, thus allowing more blood to flow through.

CALCIUM-CHANNEL BLOCKER These drugs block calcium from entering the muscle of the blood vessels, so that the vessel relaxes. By Catherine Arnst in New York

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