Safety of ibuprofen vs. paracetamol

What are readers and the public to make of the study by de Vries et al. 1 ? At a glance, it appears that the safety profiles of ibuprofen, paracetamol and the combination of the two drugs are similar. Do the results of this study, funded by the principal manufacturer of ibuprofen, hold up to closer scrutiny? This was not a prospective randomized controlled trial. It was a retrospective observational study. Importantly, we cannot assume that individuals were equally likely to have been prescribed the three options studied (ibuprofen alone, paracetamol alone or concomitant ibuprofen and paracetamol). There are some major confounding effects at play here. One might anticipate, for instance, that patients with a history of heart disease, peptic ulcers or renal disease would be less likely to have been prescribed a nonsteroidal anti‐inflammatory drug (NSAID), compared with paracetamol, in the first place. Indeed, it is clear from table 1 of the publication that there were large and statistically significant differences between the patients retrospectively allocated to the three groups across a number of baseline variables, including age and a past history of heart failure, ischaemic heart disease, cerebrovascular disease and upper gastrointestinal disease.