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In Reply: In response to Drs Violi and Cangemi, we agree that concomitant statin use may be an important consideration when evaluating the risk of cardiovascular events. From the start of the Physicians' Health Study II (PHS II) in 1997 and over the course of up to 10 years of treatment and follow-up, statin use would be expected to increase over time, mirroring population trends.¹ As a large randomized clinical trial, concomitant statin use was equally distributed in the active and placebo vitamin E and vitamin C groups on randomization into PHS II and should not confound our primary results. In addition, stratified analyses according to the presence or absence of hypercholesterolemia at baseline provided no evidence of effect modification for the association between vitamin E or C and major cardiovascular events.

Dr Evans raises an important concern about the time of day when vitamin E and C supplements were . . . [Full Text of this Article]

Howard D. Sesso, ScD, MPH
hsesso@hsph.harvard.edu

J. Michael Gaziano, MD, MPH
Brigham and Women's Hospital
Boston, Massachusetts

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