Overall, the largest benefit of aspirin (in any dose) appeared
during the fi rst year after randomization (RR = 0.62). However,
only one study (APACC) scheduled a protocol examination at
1 year; there were also substantial numbers of patients in CALGB
9270 who had early examinations. Thus, many of the examinations
that occurred within 1 year from randomization were not follow-up
examinations prescribed by protocol. Beyond 38 months after
randomization, aspirin and placebo had nearly equivalent effects
on the risk for all adenomas (RR = 0.99).
In the three studies that recruited adenoma patients (AFPPS,
ukCAP, and APACC), participants who had an examination earlier
than called for by the study protocol were likely a select (and probably
atypical) group of patients who might have had clinical indications
for the examination, such as bleeding. This selection of
participants for early examination, together with the smaller numbers
of participants in some of the follow-up intervals, complicates
interpretation of the interval-specifi c risk ratios.
We saw no differences in the rates of adverse events comparing
aspirin vs placebo in terms of mortality, myocardial infarction, major
bleeding, and all-site invasive cancer. However, there was a statistically
signifi cantly higher rate of strokes (most of which were thought
to be ischemic) among aspirin-treated participants than among
those who received placebo. There is no ready explanation for these
fi ndings. Aspirin use does seem to increase risk of hemorrhagic
stroke modestly ( 23 – 25 ). However, large randomized trials that
focused on cardiovascular outcomes have reported that in patients
without vascular disease (and who are roughly similar to participants
in the adenoma trials), aspirin had no substantial effect on ischemic
stroke risk in men ( 23 , 24 ), and may reduce this risk in women ( 23 ).
Our meta-analysis has a number of strengths. It included all
known randomized clinical trials that have tested aspirin as a
chemopreventive agent against colorectal adenomas. The trials
were generally well conducted, with high compliance and generally
high follow-up rates. The sample size in the pooled studies was
substantial, providing good statistical power. Thus, this analysis is
likely to have high validity.