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Study: Traditional diuretics better than new Less costly, traditional diuretics work better than newer medicines to treat high blood pressure and prevent some forms of heart disease, according to results from the largest hypertension clinical trial ever conducted. The long-term, multi-center trial, which was supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, compared the drugs for use in starting treatment for high blood pressure. Jan Basile, M.D., associate professor of medicine at MUSC and lead physician at the Charleston Veterans Admin-istration Hospital, headed the Low-country portion of the trial. The trial also included a cholesterol-lowering study that compared the effects of a statin drug with “usual care.” Both groups had a substantial decrease in cholesterol levels. The difference in cholesterol levels  between the groups was too small to show a difference in death rates and produced only a small, non-significant decrease in the rates of heart attacks and strokes in the statin group. “ALLHAT  (formally called the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) shows that diuretics are the best choice to treat hypertension and reduce the risk of its complications, both medically and economically,” said NHLBI director Dr. Claude Lenfant. “Many of the newer drugs were approved because they reduce blood pressure  and the risk of heart disease compared with a placebo,” he continued. “But they were not tested against each other. Yet, these more costly medications were often promoted as having advantages over older drugs, which contributed to the rapid escalation of their use. Now, at last, we  can make those needed comparisons and know which blood pressure drug to choose to begin therapy.” According to the ALLHAT high blood pressure article, diuretic use fell from 56 percent of antihypertensive prescriptions in 1982 to 27 percent in 1992. Had the pattern not changed, antihypertensive prescriptions for that period would have cost about $3.1 billion less. About 24 million Americans take drugs to lower high blood pressure, at an estimated annual cost of about $15.5 billion, the article states. ALLHAT was conducted in a variety of practice settings and included many  primary care clinics. It also included high proportions of  women, seniors, minorities, and those with type 2 diabetes. Thus, the high blood pressure results add crucial information about how well such patients do on the different drugs. High blood pressure affects about 50 million Americans, or one in four adults, and its prevalence increases with age. More than half of those over age 60 have hypertension. High blood pressure is a risk factor for heart attack and the chief risk factor for heart failure and stroke. Treatment of patients with hypertension and/or high cholesterol involves lifestyle changes, including becoming physically active, losing weight, if overweight, following a low-saturated fat, low-cholesterol eating plan, limiting dietary salt, and not smoking. If these changes alone can not lower elevated blood pressure or cholesterol enough, then drug therapy is added to the treatment. ALLHAT, which began in 1994, consisted of two trials: One compared a diuretic with newer antihypertensive drugs to start blood pressure-lowering treatment; the other compared a statin drug to usual care. All participants underwent medical checkups at 3, 6, 9, and 12 months after entry into the study and every 4 months after that. The ALLHAT blood pressure study was a randomized, double-blind trial. It involved 42,418 participants aged 55 and older, and was conducted at 623 clinics and centers across the United States and in Canada, Puerto Rico,  and the U.S. Virgin Islands. About 7,000 US veterans participated in the  study through 69 Department of Veterans Affairs clinics. Participants had hypertension (140/90 mm Hg or higher) and at least one other of the risk factors for heart disease, which include cigarette smoking and type 2 diabetes. About 47 percent of the participants were women, 47 percent non-Hispanic  white, 32 percent were black, 16 percent were Hispanic, and 36 percent had type 2 diabetes. Participants were followed on average for 4.9 years. Participants were randomly assigned to receive one of four drugs: a diuretic (chlorthalidone); a calcium channel blocker (amlodipine); an angiotensin converting enzyme (ACE) inhibitor (lisinopril); and an alpha-adrenergic blocker (doxazosin). They received additional antihypertensive drugs if their doctor thought it necessary to control their blood pressure. The alpha-adrenergic blocker arm of the study was stopped in March 2000 because those on the drug had 25 percent more cardiovascular events and were twice as likely to be hospitalized for heart failure as users of the diuretic. All three classes of drugs reported on in the December 18 issue of JAMA—diuretics, calcium channel blockers, and ACE inhibitors—have been previously shown to lower blood pressure and reduce cardiovascular complications. In head-to-head com-parisons, the diuretics were shown to be superior in treating high blood pressure and preventing cardiovascular events. As reported in JAMA, after about 5 years of followup, compared to  participants who were taking the diuretic, those on the calcium channel blocker had: On average, about a 1 mm Hg higher systolic blood pressure 38 percent higher risk of developing heart failure and 35 percent higher  risk of being hospitalized for the condition Compared to participants who were taking the diuretic, those on the ACE inhibitor had: On average, about a 2 mm Hg higher systolic blood pressure, and 4 mm Hg higher in African Americans 15 percent higher risk of stroke 40 percent higher risk of stroke for African Americans 19 percent higher risk of developing heart failure 11 percent greater risk of being hospitalized or treated for angina (chest pain) 10 percent greater risk of having to undergo a coronary revascularization (such as coronary artery bypass surgery) “The take-home message is that doctors should begin drug treatment for high blood pressure with a diuretic,” said Dr. Paul Whelton, senior vice president for Health Sciences at Tulane University in New Orleans, La., and an ALLHAT regional coordinator. “A great majority of patients can tolerate a diuretic but, for those who can't, then a calcium-channel blocker, an ACE-inhibitor, or a beta blocker may be used to start treatment. “ALLHAT's findings also indicate that most patients will need more than one drug to adequately control their blood pressure, and one of the drugs used should be a diuretic,” he continued. “Those who are now on a calcium channel blocker or an ACE inhibitor or another hypertension drug besides a diuretic should not stop taking their medication,” he added. “But they should certainly talk with their doctor about adding or switching to a diuretic for their treatment.”   Catalyst Online is published weekly, updated as needed and improved from time to time by the MUSC Office of Public Relations for the faculty, employees and students of the Medical University of South Carolina. Catalyst Online editor, Kim Draughn, can be reached at 792-4107 or by email, catalyst@musc.edu. Editorial copy can be submitted to Catalyst Online and to The Catalyst in print by fax, 792-6723, or by email to petersnd@musc.edu or catalyst@musc.edu. To place an ad in The Catalyst hardcopy, call Community Press at 849-1778.