5 78 Placebo 3,385.5 67 NSAID/analgesicb 9,731 55 NSAID nonsteroidal anti-inflammatory drug aHigh-dose aspirin: >1,000 mg/day, low-dose aspirin: ≤1,000 mg/day bParacetamol: 3,297 subjects in 5 studies (high-dose: >1,000 mg/day, low-dose: ≤1,000 mg/day); ibuprofen: 3,430 subjects in 13 studies (high-dose: >400 mg/day, Protein Tyrosine Kinase inhibitor low-dose: ≤400 mg/day); naproxen: 211 subjects in 6 studies (high-dose: >500/550 mg/day, low-dose: ≤500/550 mg/day); diclofenac: 479 subjects in 5 studies (high-dose: >25 mg/day, low-dose: ≤25 mg/day); other active

agent: 2,329 subjects in 35 studies A full protocol for the meta-analysis is available from the corresponding author. Bayer HealthCare (Leverkusen, Germany) funded the study, and Bayer employees participated in VX-689 chemical structure this research. All authors assume responsibility for the integrity of the work. 3 Results 3.1 Studies Overall, 150 publications describing 152 studies and 48,774 patients were selected; 78 of these with 19,829 subjects provided relevant data for at least one safety outcome in comparisons of selleck aspirin with placebo or an active agent (see Table 1 and see Appendix 2 in the Electronic Supplementary Material). Three studies did not describe whether subjects and investigators were blinded to study

treatment, but 69 (88 %) were double-blinded. The most frequently investigated indication was pain—the target condition in 62 studies (79 %). Subjects were aged between 16 and 75 years; about equal numbers of men and women were included. A total of 6,712.5 subjects were allocated aspirin, 3,385.5 placebo, and 9,731 an active comparator. The aspirin treatment was a single dose in 2,694 subjects (43 %). The daily dose was 500–1,000 mg in 2,874 aspirin-treated subjects (46 %) and 1,500–2,000 mg

in 2,920 subjects (47 %). 3.2 Gastrointestinal Risks Five studies comparing aspirin with placebo and five studies comparing aspirin with active comparators mafosfamide reported data on overall gastrointestinal risks, which were recorded in 4.2–18.2 % of subjects (Table 2). Aspirin subjects had higher rates than those allocated placebo (OR 2.12, 95 % confidence interval [CI] 0.95–4.76) and active comparators (OR 1.61 95 % CI 1.43–1.82) [see Table 2 and see Appendix 3 in the Electronic Supplementary Material]. Table 2 Gastrointestinal events in subjects treated with aspirin vs. comparators, all doses Outcome No. of studies No. of events/no. of subjects [%] OR [95 % CI] P valuea Aspirin Comparator Aspirin vs. placebo  Gastrointestinal events 5 23/244 [9.4] 9/213 [4.2] 2.12 [0.95–4.76] 0.55  Minor gastrointestinal events 59 173.3/3,304.5 [5.2] 116/3,170.5 [3.7] 1.46 [1.15–1.86] 0.02   Dyspepsia 22 42.1/1,296 [3.2] 14/1,172 [1.