Subgroup demographic may have skewed ALLHAT results.

To the Editor: Results of the recent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)1 have generated much excitement and controversy. The reported superior performance of thiazide diuretics brought the trial under scrutiny for reasons that include experimental design, population characteristics, primary and secondary endpoints, and statistical analysis.2,3 We propose an alternative explanation for the drug’s superior performance based on the new field of pharmacogenetics. The drug’s result may be a function of the genetic predisposition of the study’s subjects. It has been shown that more than 76% of African American men have the C825T polymorphism, a predisposition that confers a superior response to thiazides.4 As 35% of the subjects in the ALLHAT study were African American, the influence of this polymorphism could have skewed the results. Responses to angiotensin-converting enzyme inhibitor can also be predicted and may influence outcome.5 Thus, there appear to be subgroups within subject pools that 3. Messerli FH, Weber MA. ALLHAT—all hit or all miss? Key questions still remain. Am J Cardiol. 2003;92:280-281.