Published Online
on May 23, 2005

A more recent version of this article appeared on July 1, 2005

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Submitted on October 19, 2004
Revised on November 5, 2004

Major Clinical Trials of Hypertension. What Should Be Done Next?

The National Heart, Lung, Blood Institute Working Group on Future Directions in Hypertension Treatment Trials^*

From the National Heart, Lung, and Blood Institute, Bethesda, Md.

^* To whom correspondence should be addressed. E-mail: Calif001{at}mc.duke.edu.

Abstract--The National Heart, Lung, and Blood Institute assembled an ad hoc working group to evaluate opportunities for new major clinical trials in the field of hypertension. The mandate of this working group was to consider the possible designs of major randomized clinical trials focused on clinical outcomes that might merit significant investment by the National Institutes of Health. The group concluded that the ideal pragmatic clinical trial would have a factorial design and include a population at elevated risk of cardiovascular disease events. Subjects would be randomized to a target of systolic blood pressure <130 versus 130 to 150 mm Hg for adequate separation of means. Initial treatment with thiazide diuretic would be followed by randomization to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, -blocker, calcium channel blocker, or aldosterone antagonist. A third drug could be added according to a protocol. DNA, proteins, and metabolites would be collected in a sample adequate to assess differential impact of treatment on outcome as a function of genotype, proteomic, and metabolomic expression. Subclinical markers and images would also be measured in a sample of patients to develop evidence of ability to predict ultimate effect on clinical outcomes. This ideal trial would take place within a network, funded for at least a decade, aimed at connecting primary care providers with hypertension specialists. Within the network, substudies or independent studies would be coordinated to develop a continuously improving base of knowledge about the effective delivery of hypertension care.

Key words: clinical trials • drug therapy

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