dose – response relationship. Second, our analysis of cardiovascular
and bleeding events is quite limited. The entry criteria for the trials
included the absence of a need for aspirin, which is a known
cardioprotective drug. This criterion assured that the study population
was at relatively low risk of cardiovascular events, and so the
numbers of events observed in any one trial were modest.
Furthermore, none of the trials focused on cardiovascular disease,
and the clinical detail regarding individual cardiovascular events is
incomplete. Third, our exclusion of CALGB 9270 from the analysis
of adverse events because of concerns regarding the completeness
of adverse event reporting further reduced the numbers of
endpoints analyzed.