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http://www.nytimes.com/2002/12/17/health/17CND_PRES.html?tntemail0

Water Pills Best at Fighting High Blood Pressure, Study Finds

By LAWRENCE K. ALTMAN

raditional diuretics are superior to newer, more expensive drugs in lowering high blood pressure and preventing fatal and serious complications from the common condition, researchers said today in reporting the largest study ever of high blood pressure.

Diuretics, or water pills, were once the mainstay of therapy to lower blood pressure. But their use fell substantially in recent years as manufacturers heavily promoted the use of newer, costlier drugs, although the benefits and dangers of the new ones were rarely compared directly to diuretics and each other.

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The new, federally sponsored study had been long awaited because it was designed to compare the benefits of four main classes of drugs on major complications of high blood pressure in a large number of participants (more than 42,000), representing both sexes, age, large minority groups and important co-existent diseases.

High blood pressure, also known as hypertension, is the main factor underlying heart failure and stroke, and it can lead to heart attacks, health officials said.

The new study found that a diuretic, chlorthalidone, was more effective in preventing fatal and nonfatal heart attacks than members of three other classes of drugs: amlodipine, (Norvasc) a calcium channel blocker; lisinopril, (Zestril and Prinivil) an ACE inhibitor; and doxazonsin, (Cardura) an alpha-adrenergic blocker.

Health officials cautioned that patients should not stop taking their blood pressure-lowering drugs before consulting their physician.

The market for blood pressure-lowering drugs is huge. High blood pressure affects 50 million Americans, with 24 million spending $15.5 billion a year for blood pressure-lowering medication. The remainder have undetected hypertension or do know their conditions but take no drugs for it.

Because the findings from the study were consistent for all groups, they should apply to nearly all people with high blood pressure, the leaders of the study said at a news conference today at the National Heart, Lung and Blood Institute, the federal agency in Bethesda, Md., that paid $120 million for the study.

Wider use of diuretics would save patients and health care insurers more than $1 billion a year, the leaders of the study said of their findings, which are being published on Wednesday in The Journal of the American Medical Association.

Diuretics should almost always be used first when drug therapy is needed to lower high blood pressure, said Dr. Paul Whelton, a leader of the study. Dr. Whelton, a professor of epidemiology at Tulane University, said doctors should also consider switching to diuretics or adding them to existing regimens.

For patients who "need more than one medication to control blood pressure — and many people do — one should be a diuretic," said Dr. Whelton, who is also senior vice president for health sciences at Tulane.

Dr. Jackson T. Wright Jr., vice chairman of the study, who directs the high blood pressure program at Case Western Reserve University in Cleveland, said diuretics "are unsurpassed at lowering blood pressure and reducing clinical complications of hypertension."

The findings "give policymakers, health care insurers and those who develop treatment guidelines the green light to recommend the most effective, lowest-cost option for starting hypertension treatment," Dr. Whelton said.

Dr. Claude J. Lenfant, the director of the National Heart Lung and Blood Institute, said he was appointing a committee of experts to develop new national clinical guidelines for high blood pressure, which affects about one in four adults. The prevalence of hypertension increases with age; more than half of those over age 60 have hypertension, which the American Heart Association defines as a systolic blood pressure reading of 140 millimeters of mercury or more, a diastolic pressure of 90 millimeters or more, or both.

Dr. Lenfant's agency undertook the study because no one knew which of the 100 marketed anti-hypertensive drugs belonging to 7 major drug classes was best for starting treatment for high blood pressure.

Over the past decade, the Food and Drug Administration licensed the newer drugs like ACE inhibitors and calcium channel blockers because major trials documented that they lower blood pressure and reduce the incidence of heart disease among hypertensive patients. But because these studies compared the new drugs to dummy pills, and not head to head, their relative value with older drugs was unknown.

Yet manufacturers often promoted the newer, more costly medications as having advantages over older drugs, contributing to the rapid escalation of their use.

The new study involved 42,418 patients aged 55 and older who had high blood pressure and at least one other risk factor for heart disease, like diabetes or cigarette smoking.

The participants were treated in a variety of settings to resemble everyday practice as closely as possible. The settings included 623 clinics and Veterans Affairs hospitals in the United States, Puerto Rico and the United States Virgin Islands, as well as facilities in Canada. Participants agreed to let a computer decide which drugs they would take.

Doctors monitored the participants' blood pressure and health for as long as eight years, and nearly five years on average, and found that the overwhelming majority took their drugs as directed.

Compared to participants who took the diuretic, participants taking the ACE inhibitor had, on average, a systolic blood pressure about 2 millimeters mercury higher; blacks in the group were 4 millimeters higher.

There was a 15 percent higher risk of stroke over all for the ACE inhibitor group, and a 40 percent higher risk among blacks. The risk for developing heart failure among all groups was 19 percent higher and the risk for being hospitalized or treated for the chest pains of angina was 11 percent higher. Further, the risk of needing a coronary bypass operation or angioplasty was 10 percent higher.

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