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March 1, 1997

Analysis of clinical trials yields new appreciation of low-dose diuretic therapy for high blood pressure

Diuretics and beta blockers should continue to be first-line treatments for high blood pressure because of their safety and effectiveness, researchers conclude after analyzing a number of clinical trials.
Dr. Bruce M. Psaty, associate professor of medicine, epidemiology and health services at the University of Washington, and colleagues report their findings in the March 5 issue of the Journal of the American Medical Association.

“Compared with placebo, low-dose diuretic therapy used as first-line therapy was effective in preventing not only stroke and congestive heart failure but also coronary disease and total mortality in patients with high blood pressure,” said Psaty.

The researchers analyzed the results of 18 randomized clinical trials that lasted at least one year. Their analysis showed that overall risk reductions in patients on diuretics, compared to those on placebos, were 42 percent for congestive heart failure, 34 percent for stroke, 28 percent for coronary disease, and 10 percent for total mortality. Beta blockers were also effective in preventing stroke and congestive heart failure, the analysis showed.

“These findings provide strong support for the current national guidelines, which recommend low-dose diuretics and beta blockers as first line agents in the drug treatment of high blood pressure,” said Psaty.

The researchers note that a number of experts favor newer antihypertensive agents, including ACE inhibitors and calcium-channel blockers, as first-line therapy for high blood pressure whenever there are “special indications.” However, Psaty and colleagues note that the newer agents have not been evaluated in terms of their ability to prevent stroke and heart disease in large clinical trials, while several recent observational studies have raised questions about the safety of calcium-channel blockers. Several large clinical trials evaluating the newer agents are under way or planned, but their results will not be available for several years.

“The clinical rationale for using these newer agents rather than low-dose diuretics and beta blockers, which are known to be safe and effective as first-line agents, needs to be a compelling one,” said Psaty. “When measured in terms of health outcomes that are important to patients, there are few special indications for the newer agents to be used as first-line antihypertensive therapy.

“ACE inhibitors, for instance, are known to be effective in patients with congestive heart failure and in insulin-dependent diabetes patients with renal disease. For other ‘special indications,’ the potential benefits must be weighed against the known health risks of withholding the proven first-line therapies currently recommended by the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure.”

The researchers conclude: “Until the results of large long-term clinical trials evaluating the effects of calcium-channel blockers and ACE inhibitors on cardiovascular disease incidence are completed, the available scientific evidence provides strong support for the current national guidelines, which recommend diuretics and beta blockers as first-line agents and low-dose therapy for all anti-hypertensive agents.”

The research is supported by grants from the National Heart, Lung and Blood Institute and the National Institute on Aging.

Co-authors are Nicholas L. Smith, Dr. David S. Siscovick, Dr. Thomas D. Koepsell, Dr. Noel S. Weiss, Dr. Susan R. Heckbert, Dr. Rozenn N. Lemaitre, all of the University of Washington; and Dr. D. Furberg of the Bowman Gray School of Medicine.

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