Gastrointestinal bleeding
We identified 3229 gastrointestinal bleeding events, 282 (8.7%) of which were fatal. A total of 327 events were registered during NSAID treatment. The overall crude incidence rate was 0.8 (95% confidence interval 0.7 to 0.8) events per 100 person years The crude incidence rate of gastrointestinal bleeding on NSAID treatment was 2.1 (1.8 to 2.4) events per 100 person years without concurrent PPI treatment and 1.8 (1.4 to 2.4) with concurrent PPI treatment (fig 3⇓). After multivariable adjustment for baseline differences, use of PPIs concurrently with combined antithrombotic and NSAID treatment was associated with a significantly lower risk of gastrointestinal bleeding (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) compared with treatment without concurrent PPIs (fig 3⇓). Compared with combined antithrombotic and NSAID treatment (without concurrent PPI), taking antithrombotics only (without NSAID or PPI) or antithrombotics with concurrent PPI treatment (without NSAID) were each associated with a lower risk of gastrointestinal bleeding. The bleeding risk associated with concurrent PPI and NSAID treatment was similar for each antithrombotic regimen (supplementary table 3). PPIs taken concurrently with NSAID and dual antithrombotic therapy were associated with a reduced risk of gastrointestinal bleeding (incidence rate 2.5 (1.3 to 4.8) events per 100 person years) compared with NSAID and dual antithrombotic therapy without concurrent PPIs (5.2 (3.9 to 6.8) events per 100 person years) (hazard ratio 0.41, 0.20 to 0.84).