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Benefits and harm of paracetamol and ibuprofen in combination for post‐operative pain: Pre‐planned subgroup analyses of the multicenter, randomized PANSAID trial
Author(s) -
Thybo Kasper H.,
HägiPedersen Daniel,
Wetterslev Jørn,
Dahl Jørgen B.,
Jakobsen Janus C.,
Pedersen Niels Anker,
Jakobsen Karina,
Bülow Hans Henrik,
Ibsen Louise,
Overgaard Søren,
Mathiesen Ole
Publication year - 2020
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.13496
Subject(s) - medicine , subgroup analysis , ibuprofen , adverse effect , randomized controlled trial , opioid , regimen , post hoc analysis , number needed to harm , analgesic , acetaminophen , tramadol , population , anesthesia , relative risk , pharmacology , number needed to treat , confidence interval , receptor , environmental health
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 find an increase in risk of harm when using ibuprofen vs paracetamol. The aim of this subgroup analysis was to investigate the differences in benefits and harms of the interventions in different subgroups. We hypothesized that the intervention effects would differ in subgroups with different risk of pain or adverse events. Methods In these pre‐planned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between (a) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists (ASA) score, and type of anesthesia) and morphine consumption, and (b) subgroups (sex, age, use of non‐steroidal anti‐inflammatory drugs (NSAIDs), and ASA score) and serious adverse events. Results Test of interaction between age and the pairwise comparison between paracetamol 1 g vs paracetamol 0.5 g + ibuprofen 200 mg ( P = .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 pre‐planned subgroup analyses did not suggest that patients in the investigated subgroups benefitted differently 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.