Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.
In Reply: Dr Choudhury suggests that selection
bias may have contributed to the difference in outcomes with clopidogrel pretreatment
of less vs greater than 6 hours. As we noted in our article, there was no
difference in patient baseline characteristics based on time of pretreatment,
and all subgroups of patients derived similar benefit, or lack of it, based
on the timing of pretreatment. Nonetheless, it is possible that unmeasured
variables differed between the 2 groups. Choudhury, as well as Dr Bridges
and Dr Borja and colleagues highlight the methodological issues with evaluating
multiple interventions in clinical trials and the lack of a factorial design
in our study. We agree that rerandomization would have been ideal. However,
a lack of any plausible mechanism for a single loading dose of clopidogrel
being able to prevent stokes, spontaneous myocardial infarctions, and death
1 to 12 months following its administration helped us decide to choose the
design we did rather than the admittedly preferred factorial design suggested
by Bridges and Borja and colleagues. Such a design would not only have been
far more costly, but would have also required a much larger sample size.
Steinhubl SR, Berger PB, Mann III JT, Fry ETA, DeLago A, Wilmer C, Topol EJ. Clopidogrel and Percutaneous Coronary Interventions. JAMA. 2003;289(15):1925–1927. doi:10.1001/jama.289.15.1925-a
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