Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations

Background
The use of low-dose aspirin has been reported to be associated with an
increased risk of upper gastrointestinal complications (UGIC). The coating of
aspirin has been proposed as an approach to reduce such a risk. To test this
hypothesis, we carried out a population based case-control study.

      Methods
      We identified incident cases of UGIC (bleeding or perforation) aged 40 to 79

years between April 1993 to October 1998 registered in the General Practice
Research Database. Controls were selected randomly from the source population.
Adjusted estimates of relative risk (RR) associated with current use of aspirin
as compared to non use were computed using unconditional logistic
regression.

      Results
      We identified 2,105 cases of UGIC and selected 11,500 controls. Among them,

287 (13.6%) cases and 837 (7.3%) controls were exposed to aspirin, resulting in
an adjusted RR of 2.0 (1.7-2.3). No clear dose-effect was found within the
range of 75-300 mg. The RR associated with enteric-coated formulations (2.3,
1.6-3.2) was similar to the one of plain aspirin (1.9, 1.6-2.3), and no
difference was observed depending on the site. The first two months of
treatment was the period of greater risk (RR= 4.5, 2.9-7.1). The concomitant
use of aspirin with high-dose NSAIDs greatly increased the risk of UGIC (13.3,
8.5-20.9) while no interaction was apparent with low-medium doses (2.2,
1.0-4.6).

      Conclusions
      Low-dose aspirin increases by twofold the risk of UGIC in the general

population and its coating does not modify the effect. Concomitant use of
low-dose aspirin and NSAIDs at high doses put patients at a specially high risk
of UGIC.