Traditional water pills, or diuretic medications, were as good or better than more expensive, newer drugs in treating high blood pressure and preventing related heart disease complications, according to an article in the Dec. 18 issue of The Journal of the American Medical Association (JAMA).

Jackson T. Wright, Jr., M.D., Ph.D., professor of medicine at Case Western Reserve University in the division of hypertension at University Hospitals of Cleveland, was one of the co-chairs of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study. The diuretics were compared to ACE inhibitors and calcium channel blockers.

Treatment and complications among the 50 to 60 million people in the United States with hypertension are estimated to cost $37 billion annually, with antihypertensive drug costs alone accounting for an estimated $15.5 billion per year. Antihypertensive therapy is well established to reduce hypertension-related illness and death, but the optimal first-step therapy is unknown.

Antihypertensive therapies have included diuretics and beta-blockers and several newer classes of agents such as angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs). Over the past decade, major placebo-controlled trials have documented that ACE inhibitors and CCBs reduce cardiovascular events in individuals with hypertension. However, their relative value compared with older, less expensive agents such as diuretics and beta-blockers remains unclear, and there has been considerable uncertainty regarding effects of some classes of antihypertensive drugs on risk of coronary heart disease (CHD).

Wright, Barry R. Davis, M.D., Ph.D., from the University of Texas-Houston Health Science Center, and ALLHAT investigators conducted a randomized, double-blind, multicenter, clinical trial-the gold standard of clinical trials-designed to determine whether the occurrence of fatal heart disease or nonfatal heart attack is lower for high-risk patients with hypertension treated with a calcium channel blocker (amlodipine) or an ACE inhibitor (lisinopril), each compared with thiazide (a type of diuretic, chlorthalidone).

The trial was conducted from February 1994 through March 2002 and included 33,357 participants aged 55 years or older with hypertension and at least one other coronary heart disease risk factor. They were recruited from 623 centers in the United States, Canada, Puerto Rico and the U.S. Virgin Islands, with follow-up of approximately four to eight years.

The researchers found that the primary outcome of combined fatal CHD or non-fatal heart attack occurred in 2,956 participants.

"Neither amlodipine [6-year rate, 11.3 percent] nor lisinopril [6-year rate, 11.4 percent] was superior to chlorthalidone [6-year rate, 11.5 percent] in preventing major coronary events or in increasing survival," the authors write. "Chlorthalidone was superior to amlodipine (by about 25 percent) in preventing heart failure (HF), overall, and for hospitalized or fatal cases, although it did not differ from amlodipine in overall CVD prevention. Chlorthalidone was superior to lisinopril in lowering BP and in preventing aggregate cardiovascular events, principally stroke, HF, angina and coronary revascularization."

"In conclusion, the results of ALLHAT indicate that thiazide-type diuretics should be considered first for pharmacologic therapy in patients with hypertension. They are unsurpassed in lowering BP, reducing clinical events, and tolerability, and they are less costly," the authors write. "Since a large proportion of participants required more than one drug to control their BP, it is reasonable to infer that a diuretic be included in all multidrug regimens, if possible. Although diuretics already play a key role in most antihypertensive treatment recommendations, the findings of ALLHAT should be carefully evaluated by those responsible for clinical guidelines and be widely applied in patient care."

In an accompanying editorial, Lawrence J. Appel, M.D., M.P.H., from Johns Hopkins University, Baltimore, writes that "quite simply, [ALLHAT] is one of the most important trials of antihypertensive drug therapy. For decades, experts have passionately debated which class of drugs should be initial therapy for hypertension. Resolution of this issue, which has enormous clinical, public health and economic implications, comes at a time of intense pressure to reduce health care costs while improving clinical outcomes. In this setting, the ALLHAT results, reported in this issue of The Journal, are particularly noteworthy, because there is no cost-quality tradeoff; the most effective therapy was also the least expensive."

Wright was interviewed by several news media about this article, including the New York Times, Time Magazine, Associated Press and the Wall Street Journal.

The study was supported by the National Heart, Lung and Blood Institute (NHLBI). ALLHAT investigators received contributions of study medications supplied by Pfizer (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril) and Bristol-Myers Squibb (pravastatin) and financial support provided by Pfizer. For the financial disclosures of the authors, please see the JAMA article.