High- vs. low-dose diclofenac and cardiovascular risks:a target trial emulation

Aims To examine the dose dependency of diclofenac's cardiovascular risks. Methods and results Using Danish health registries and the target trial emulation design, we conducted a series of 300 nationwide cohort studies during 1996–2020, each mimicking the strict design criteria of a clinical trial. Adults eligible for inclusion had no recent non-steroidal anti-inflammatory drug prescriptions, contraindications (gastrointestinal diseases, thrombocytopenia, or heart failure), or conditions with low adherence (dementia or psychiatric disease). Diclofenac initiators were compared to healthcare-seeking non-initiators and head-to-head using an approximated high dose of ≥150 mg/day vs. low dose of Conclusions Initiators of high- and low-dose diclofenac had comparably increased cardiovascular risks. This finding provides evidence against the assumption that low-dose diclofenac is risk-neutral.