Risk of XXXX associated with non-steroidal anti-inflammatory drugs and paracetamol: a population-based case-control study.

@entity1 @entity385
OBJECTIVE: To assess the risk of non-fatal @entity385 associated with non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied. METHODS: We performed a population-based case-control study. @entity1 were considered exposed if they were on treatment within a 30-day window before the index date. We estimated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression. RESULTS: Two thousand eight hundred and eighty-eight cases and 20  000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR  =  1.03; 95% CI, 0.90-1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR  =  1.53; 95% CI, 1.19-1.97), in particular when used at high doses (OR  =  1.62; 1.06-2.46), over long-term periods (>  365  days; OR  =  2.39; 1.52-3.76) and in @entity1 with a high background CV risk (OR  =  1.78; 1.23-2.58), as well as with aceclofenac when used at high doses (OR  =  1.67; 1.05-2.67), in long-term treatments (OR  =  2.00; 1.14-3.53) and in @entity1 with CV risk factors (OR  =  2.33; 1.40-3.87). No association was found with ibuprofen (OR  =  0.94; 0.76-1.17) or naproxen (OR  =  0.68; 0.36-1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR  =  0.97; 0.85-1.10) or in @entity1 at high CV risk (OR  =  0.94; 0.78-1.14). CONCLUSIONS: Diclofenac and aceclofenac increase the risk of @entity385 while ibuprofen and naproxen do not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate the risk. Paracetamol does not increase the risk, even in @entity1 with a high background CV risk.
