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Diuretics Excel in Drug Comparison Trial Involving Hypertension/Metabolic Syndrome


Diuretics were associated with reduced heart disease in a drug comparison trial involving 23,077 people with both high blood pressure and the metabolic syndrome, a cluster of risk factors for heart disease, report researchers from The University of Texas School of Public Health and Case Western Reserve University in the Jan. 28 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals. The cardiac benefits connected with diuretics were particularly pronounced in blacks, who have a high incidence of high blood pressure or hypertension.

UT-Houston’s Barry Davis, M.D., Ph.D., Sara Pressel, M.S., and Charles Baimbridge.

“In hypertensive patients with metabolic syndrome, initial treatment for hypertension should include a diuretic,” said senior author Barry Davis, M.D., Ph.D., professor of biostatistics and the director of the Coordinating Center for Clinical Trials at the UT School of Public Health. “Diuretics are preferred over other major classes of blood pressure medications to prevent one or more forms of cardiovascular disease.”

High blood pressure is one of the risk factors included in the metabolic syndrome along with diabetes or pre-diabetes, excessive belly fat, high triglyceride levels, or low levels of high-density lipoprotein (“good” cholesterol). It is estimated that about 40 percent of adults age 60 years or older can be classified as having the metabolic syndrome.

According to Davis, the James W. Rockwell Professor of Public Health, diuretics, also known as “water pills,” offered greater protection against cardiovascular disease including heart failure, and were at least as effective for lowering blood pressure when compared to three other classes of blood pressure medications. “The newer medications tend to produce better glucose and cholesterol values but the diuretics tend to generate better patient outcomes,” he said.

“This is an important study that provides a new insight into diuretic therapy for blood pressure control, particularly in patients with the metabolic syndrome who are subject to heart failure,” said K. Lance Gould, M.D., professor in the Division of Cardiology at the UT Medical School at Houston.

“While the primary endpoint showed no difference between drug treatment groups, subset analysis of the metabolic syndrome showed less heart failure when diuretics are used. This subset analysis emphasizes the value of diuretic treatment in patients with the metabolic syndrome who are subject to heart failure,” said Gould, the Martin Bucksbaum Distinguished University Chair.

Diuretics lower blood pressure by reducing fluid from blood. The other classes of blood pressure medication tested during the trial included: calcium channel blockers which relax blood vessels; ACE inhibitors which prevent the formation of a hormone which causes blood vessels to narrow; and alpha blockers, which reduce nerve impulses that constrict vessels.

Among patients with the metabolic syndrome (7,327 black and 15,750 white patients), the calcium channel blocker, ACE inhibitor and alpha-blocker had higher rates of heart failure compared with the diuretic; the ACE inhibitor and the alpha-blocker also had an increased risk of combined cardiovascular disease.

The latest findings stem from a landmark investigation based at the UT School of Public Health, which in 2002 established that diuretics were “as good or better” than three other classes of medications for high blood pressure during a multi-center, randomized, double-blind, clinical trial. The investigation is called ALLHAT - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Also contributing to the study from the UT School of Public Health were Sara Pressel, M.S., a faculty associate in biostatistics and co principal investigator of ALLHAT, and Charles Baimbridge, a graduate student in biostatistics.

“This study once again demonstrates that thiazide-type diuretics are an effective and inexpensive therapy in all patients at risk for heart disease, regardless of ethnicity or metabolic status. The robust size of this study confirms their conclusions,” said Philip R. Orlander, M.D., professor and interim chair in the Department of Medicine at the UT Medical School at Houston.

“Diuretics were thought to be poor first choices for individuals with diabetes or the metabolic syndrome because of their known adverse impact on lipid profiles and glucose. One of the major contributions of the ALLHAT study is to disprove this hypothesis. The results of this study should be immediately adopted into clinical practice,” Orlander said.

This study titled “Clinical Outcomes by Race in Hypertensive Patients With and Without the Metabolic Syndrome” was supported by the National Heart, Lung, and Blood Institute and by the Pfizer pharmaceutical company. Jackson T. Wright, Jr., M.D., Ph.D., Case Western Reserve University, was lead author.


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