BACKGROUND: The 'Paracetamol and Ibuprofen in Combination' (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not findan increase in risk of harm when using ibuprofen versus paracetamol. The aim of this subgroup analysis was to investigate differences in benefits and harms of the interventions in different subgroups. We hypothesized the intervention effects would differ in subgroups with different risk of pain or adverse events.

METHODS: In these preplanned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between 1) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists score, and type of anesthesia) and morphine consumption, and 2) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs, and American Society of Anesthesiologists score) and serious adverse events.

RESULTS: Test of interaction between age and the pairwise comparison between paracetamol 1 g versus paracetamol 0.5 g + ibuprofen 200 mg (P=0.009) suggested lower morphine consumption in patients>65 years. However, post hoc analyses of related outcomes showed no interaction for this pairwise comparison. All other tests of interaction regarding both benefit and harm were not statistically significant.

CONCLUSION: These preplanned subgroup analyses did not suggest that patients in the investigated subgroups benefitteddifferently from a basic non-opioid analgesic regimen consisting of paracetamol and ibuprofen. Further, there was no evidence of subgroup heterogeneity regarding harm and use of ibuprofen. Because of reduced statistical power in subgroup analyses we cannot exclude clinically relevant subgroup heterogeneity.