BMJ, doi: 10.1136/bmjusa.03030003, (Published 12 April 2003)

Letter

Rapid responses from bmj.com: Somewhat flawed conclusion

Following are edited excerpts from the Rapid Responses generated by this article, which can be read in their entirety at http://bmj.com/cgi/eletters/326/7380/61" —Editor

D G Hackam

Department of Medicine, McMaster University, Hamilton, Ontario, Canada. danielhackam@hotmail.com

From BMJ USA 2003;Mar:129

In an otherwise excellent analysis of the ALLHAT study, Williams ends with the following conclusion: "The key message from this trial is that what matters most is getting blood pressure controlled, and that this is overwhelmingly more important than the means."

ALLHAT showed that all blood pressure drugs were not "created" equal. Williams correctly points out important differences in the secondary cause-specific end points between chlorthalidone and its active comparators: doxazosin (increased congestive heart failure), lisinopril (increased stroke and coronary end points), and amlodipine (increased stroke). For this very reason, the Data Safety Monitoring Board of the ALLHAT trial recommended discontinuance of the doxazosin arm.

There are characteristics of blood pressure drugs other than their effect on "hard end points" that are as important as "getting blood pressure controlled." These include cost, adverse effects, ease of use (once daily versus multi-daily dosing), and interactions with other drugs. In all aspects, thiazide-type diuretics come up tops as first-line agents. This was amply shown in the SHEP and MRC studies, where thiazide diuretics were associated with a greater than 40% reduction in the risk of stroke in patients with isolated systolic hypertension; these studies were conducted and completed more than a decade ago. ALLHAT also demonstrated the differences in tolerability between agents and the particular difficulty in controlling blood pressure to target levels, especially with ACE inhibitors in black patients.

In choosing a therapeutic agent to lower blood pressure and reduce cardiovascular risk, one must look at not only the effect on blood pressure, but also important clinical end points we are aiming to prevent, as well as cost and tolerability.


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