And also collected information on duration dose and

and also collected information on duration, dose, and indi-
cation for use. While some underreporting of aspirin use by
self-report has been noted in other studies, reporting accuracy
tends to improve with more frequent and regular use. 43,44 As
information on aspirin use was obtained prospectively in this
study, any misclassification of aspirin use due to inaccurate
reporting is likely to be nondifferential, leading most likely
to an attenuation of the effects of aspirin. 45 Although we
relied on self-reported data on comorbidities, the validity of
self-reported data has been shown to be generally good for
heart disease, stroke, hypertension, diabetes, and other medi-
cal conditions. 27–31 It is possible that the elevated mortality
risks we observed were due to other conditions not captured
in the questionnaires; however, the unidentified comorbidities
would need to be strongly correlated with both aspirin use
and mortality to have a substantial impact on our findings.
Cardiovascular mortality risk estimates for individuals tak-
ing aspirin more than once daily remained elevated even after
excluding deaths in the first 5 years of follow-up, minimizing
the likelihood that heavy aspirin users were treating symp-
toms related to end-stage disease.
In conclusion, our study confirms the potential utility
of daily aspirin for the secondary prevention of cardiovas-
cular mortality, but suggests caution for its use among those
without a history of cardiovascular disease. Consistent find-
ings across 2 large cohorts suggest that more than once daily
use of aspirin does not provide a reduction in mortality and
may be associated with an increased risk of death, particularly
among individuals without a history of cardiovascular disease.
Although further studies are needed to confirm these findings,
our study highlights the need to evaluate important long-term
health risks of aspirin across a broad range of common use
patterns and to fully consider the risks and benefits before
making public health recommendations.
ACKNOWLEDGMENTS
The authors thank the participants from the NIH-AARP
and PLCO cohorts for their excellent cooperation in these
studies. The authors also thank Mr. Adam Risch and Mr. John
Commins, Information Management Services, Inc. for their
assistance in the data analysis. The content of this publication
does not necessarily reflect the views or policies of the
Department of Health and Human Services nor does mention
of trade names, commercial products, or organizations imply
endorsement by the US Government. All statements in this
report, including its findings and conclusions, are solely those
of the authors and do not necessarily represent the views of
the Patient-Centered Outcomes Research Institute (PCORI),
its Board of Governors or Methodology Committee.