Texas Medical Center NEWS


Vol. 25, No. 2		February 1, 2003

Landmark National Study Finds Diuretics Work Best for Hypertension

Faculty at The University of Texas School of Public Health at Houston are credited with coordinating the largest clinical trial for hypertension ever conducted, which found that diuretics work better than newer medications to treat high blood pressure and prevent one or more forms of heart disease. Study investigators and officials of the National Heart, Lung and Blood Institute of the National Institutes of Health announced the finding at a December press conference in Washington, D.C.

“The high blood pressure results add crucial information about how well such patients do on the different drugs,” said Barry R. Davis, M.D., Ph.D., professor of biometry and director of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, or ALLHAT, Clinical Trials Center at the School of Public Health. The $103.2 million contract awarded from the NHLBI in 1993 to coordinate ALLHAT was the largest contract ever awarded to a unit of The University of Texas Health Science Center at Houston.

Findings of the ALLHAT blood pressure study, which included more than 40,000 participants, bring important news for the 50 million Americans suffering from high blood pressure, especially the 24 million who are taking drugs to lower their blood pressure, Davis said. They and their doctors now should know that the first-choice drug should almost always be a diuretic, with other types added later if needed.

“The ALLHAT study is an important one,” said UT Health Science Center at Houston President James T. Willerson, M.D., a world-renowned cardiologist. “The information provided will be very useful in the care of patients with elevated blood pressure and lipid abnormalities. We are very proud of the role that Professor Barry Davis played in directing the ALLHAT Clinical Trials Center at The University of Texas School of Public Health at Houston.”

The ALLHAT study generated national media coverage following publication of two articles in the Dec. 18 issue of the Journal of the American Medical Association. Articles and details of the study and its findings can be found at the study’s Web site at http://www.allhat.org.

Key Study Findings

•Because of their superiority in preventing one or more major forms of cardiovascular disease and their lower cost, thiazide-type diuretics should be the drugs of choice for initial treatment of hypertension in most patients requiring drug therapy.

•In patients who cannot tolerate a diuretic, therapy can be started with ACE inhibitors, calcium channel blockers or beta-blockers. These medications have been shown to have cardiovascular disease benefits compared with placebos. Alpha-blockers, however, should not be considered for initial therapy.

•Most hypertensive patients require more than one medication to adequately control blood pressure, and diuretics should be part of most multidrug regimens. Behavioral approaches (e.g., eating plan, physical activity and weight loss) also should be taken.

•Physicians and patients should consider changing antihypertensive therapy to a thiazide-type diuretic if a different type of medication is currently taken – even if the patient’s blood pressure is well controlled with the alternate medication. The patient is likely to benefit from the enhanced effectiveness of the diuretic as well as the reduced cost of the drug.

The project consisted of two clinical trials. One compared a diuretic with newer and more expensive antihypertensive drugs used to lower blood pressure, to ascertain which was best at preventing cardiovascular outcomes. The other compared a statin drug to usual care in lowering cholesterol levels to determine if treatment would lower the occurrence of deaths over the study period.

Antihypertensive Trial

The antihypertensive trial found that the diuretic chlorthalidone, a traditional and less expensive medication, worked better than a calcium channel blocker, an ACE inhibitor and an alpha-blocker in preventing one or more forms of cardiovascular disease, most notably heart failure. National Heart, Lung and Blood Institute director Claude Lenfant, M.D., and the ALLHAT investigators explained that the results show that diuretics should be the first choice for initial therapy for hypertension. The authors concluded that diuretics are unsurpassed in lowering blood pressure, reducing clinical events and tolerability, and they are less costly.

In an accompanying editorial, Lawrence J. Appel, M.D., of Johns Hopkins University, wrote that the ALLHAT results “are particularly noteworthy because there is no cost-quality tradeoff; the most effective therapy was also the least expensive.”

“ALLHAT was conducted in a variety of practice settings and included many primary care clinics,” Davis said. “It also included high proportions of women, seniors, minorities and those with Type 2 diabetes.”

The ALLHAT blood pressure study was a randomized, double-blind trial involving 42,418 participants age 55 and older, conducted at 623 clinics and centers across the United States and in Canada, Puerto Rico and the U.S. Virgin Islands.

While the ALLHAT clinical trial closed out last March, Davis said the data promises publication will continue for years, including cost-effectiveness evaluation of treatments; results in important subgroups of patients such as those with diabetes and renal disease; renal outcomes in patients with hypertension; and genetics of hypertension and treatment.

Cholesterol-Lowering Trial

The second ALLHAT clinical trial comparing use of the statin drug pravastatin with usual care in reducing cholesterol levels found that both study groups had substantial reductions in cholesterol. Investigators found no significant differences in death rates and coronary heart disease between the two groups, which totaled more than 10,000 participants.

The study results do not alter current cholesterol treatment guidelines, which are based on a series of clinical trials with larger cholesterol reductions than that observed in ALLHAT. Thus, cholesterol lowering by lifestyle changes and drug treatment is recommended to reduce cardiovascular disease morbidity and mortality.

Impact of Findings

ALLHAT’s findings will have a great impact beyond improving cardiovascular health, said Davis.

Because diuretics cost around 6 to 20 times less per pill than the other classes, prescribing them first would dramatically reduce health care costs. Annual U.S. antihypertensive drug costs are an estimated $15 billion.

Also, finding that newer drugs do not necessarily mean better drugs will re-ignite arguments surrounding the approval process, Davis said. Approval of a drug only requires proof of efficacy compared with a placebo, not whether it works better than existing therapies. During a year in which another U.S. government-funded trial disproved the theory that hormone replacement therapy protects women against heart disease, the findings from ALLHAT raise the question of whether government should either force manufacturers to compare their new drugs with existing remedies when seeking marketing approval or conduct such studies itself.

Other investigators and staff of the ALLHAT Clinical Trials Center at the School of Public Health include Charles Ford, Ph.D., associate professor of biometry; Kay Dunn, Ph.D., associate professor of biometry; Linda Piller, M.D., assistant professor of biological sciences; Sara Pressel, ALLHAT project manager; and ALLHAT assistant project managers Judy Bettencourt, Lara Simpson, Barbara DeLeon, and Joe Blanton.

– The University of Texas Health Science Center at Houston Office of Public Affairs

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