Abstract
Background and AimsData regarding the influence of dose and duration of aspirin use on risk of gastrointestinal bleeding are conflicting.MethodsWe conducted a prospective cohort study of 32,989 men enrolled in the Health Professionals Follow-up Study (HPFS) in 1994 who provided biennial aspirin data. We estimated relative risk of major gastrointestinal bleeding requiring hospitalization or a blood transfusion.ResultsDuring 14 years of follow-up, 707 men reported an episode of major gastrointestinal bleeding over 377,231 person-years. After adjusting for risk factors, regular aspirin use (≥2 times/week) had a multivariate relative risk (RR) of gastrointestinal bleeding of 1.32 (95% confidence interval [CI], 1.12–1.55) compared to non-regular use. The association was particularly evident for upper gastrointestinal bleeding (multivariate RR, 1.49; 95% CI, 1.16–1.92). Compared to men who denied any aspirin use, multivariate RRs of upper gastrointestinal bleeding were 1.05 (95% CI 0.71–1.52) for men who used 0.5–1.5 standard tablets/week, 1.31 (95% CI 0.88–1.95) for 2–5 aspirin/week, 1.63 (95% CI, 1.15–2.32) for 6–14 aspirin/week and 2.40 (95% CI, 1.10–5.22) for >14 aspirin/week (Ptrend<0.001). The relative risk also appeared to be dose-dependent among short-term users <5 years; Ptrend<.001) and long-term users (≥5 years; Ptrend = 0.015). In contrast, after controlling for dose, increasing duration of use did not appear to be associated with risk (Ptrend = 0.749).ConclusionsRegular aspirin use increases the risk of gastrointestinal bleeding, especially from the upper tract. However, risk of bleeding appears to be more strongly related to dose than to duration of use. Risk of bleeding should be minimized by using the lowest effective dose among short-term and long-term aspirin users.
Highlights
Randomized trials have demonstrated that aspirin lowers the risk of myocardial infarction among patients with prior cardiovascular disease as well as those with cardiovascular risk factors [1,2,3]
Participants who used aspirin tended to be older, had higher body mass indices, and were more likely to have diabetes, hypertension, hypercholesterolemia, coronary artery disease, and osteoarthritis compared to men who denied no aspirin use
{One standard tablet is 325 mg of aspirin. {Body mass index is weight in kilograms divided by the square of the height in meters. 1Current non-steroidal anti-inflammatory drug (NSAID) use is defined as regular intake of at least 2 times per week. doi:10.1371/journal.pone.0015721.t001
Summary
Randomized trials have demonstrated that aspirin lowers the risk of myocardial infarction among patients with prior cardiovascular disease as well as those with cardiovascular risk factors [1,2,3]. The effect of duration of aspirin use on risk of gastrointestinal bleeding remains unclear. Some data suggest that over time the gastrointestinal mucosa adapts to the adverse effects of aspirin This hypothesis has been supported by human studies which have suggested that shorter duration of aspirin use was associated with increased risk of gastrointestinal bleeding [8,9]. Other studies show that bleeding risk is cumulative over time [10] These inconsistent results may be due to heterogeneous study populations, small sample sizes, data on only a limited range of doses, and relatively short duration of follow-up. Data regarding the influence of dose and duration of aspirin use on risk of gastrointestinal bleeding are conflicting
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