Self-selected posttrial aspirin use and subsequent cardiovascular disease and mortality in the physicians' health study.
BACKGROUND
The randomized aspirin component of the Physicians' Health Study (PHS) was terminated early, after 5 years, primarily because of the emergence of a statistically extreme (P<.00001) 44% reduction of first myocardial infarction (MI) among those assigned to aspirin. As a result, there were insufficient numbers of strokes or cardiovascular disease (CVD)-related deaths to evaluate these end points definitively.


METHODS
Data on self-selected aspirin use were collected until the beta carotene component ended as scheduled after 12 years. Posttrial use of aspirin was assessed at the 7-year follow-up among 18 496 participants with no previous reported CVD. Randomized and posttrial observational results in the PHS were compared, and differences between those self-selecting aspirin and those not were examined.


RESULTS
At 7 years, 59.5% of participants without CVD reported self-selected aspirin use for at least 180 d/y, and 20.8% for 0 to 13 d/y. Use was significantly associated with family history of MI, hypertension, elevated cholesterol levels, body mass index, alcohol consumption, exercise, and use of vitamin E supplements. In multivariate analyses, self-selected aspirin use for at least 180 vs 0 to 13 d/y was associated with lower risk for subsequent MI (relative risk [RR], 0.72; 95% confidence interval [CI], 0.55-0.95), no relation with stroke (RR, 1.02; 95% CI, 0.74-1.39), and significant reductions in CVD-related (RR, 0.65; CI, 0.47-0.89) and total mortality (RR, 0.64; CI, 0.54-0.77).


CONCLUSIONS
These associations between self-selected aspirin use and CVD risk factors increase the likelihood of residual confounding and emphasize the need for large-scale randomized trials, such as the ongoing Women's Health Study, to detect reliably the most plausible small to moderate effects of aspirin in the primary prevention of stroke and CVD-related death.
Cook
N R
NR
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02215-1204, USA. ncook@rics.bwh.harvard.edu
Hebert
P R
PR
Manson
J E
JE
Buring
J E
JE
Hennekens
C H
CH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000517:prevention & control*; D015986:Confounding Factors, Epidemiologic; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012306:Risk; D012307:Risk Factors; D012651:Self Medication; D020521:Stroke / Q000401:mortality* / Q000517:prevention & control*
D001241:Aspirin