Dose-dependency of diclofenac's cardiovascular risks: a series of nationwide emulated trials

Abstract

Funding Acknowledgement: Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation Background: The dose dependency of the adverse effects of diclofenac remains poorly understood. Purpose: To examine the dose-related cardiovascular risks associated with diclofenac initiation Methods: We used Danish nationwide health registries (1999-2018) to conduct a series of emulated trials (n=285). Eligible adults had no recent NSAID fillings, contraindications, or conditions with low adherence. Individuals eligible for inclusion were ≥18 years with (1) ≥90 days continuous prescription records prior to diclofenac initiation (baseline); (2) no NSAID prescriptions ≤90 days before enrollment, and (3) no exclusion criteria. Exclusion criteria reflected likelihood of low adherence to treatment (dementia, schizophrenia, or antipsychotic drug use) and labeled contraindications (ul-cer disease/anti-ulcer drugs, gastrointestinal bleeding, inflammatory bowel disease, thrombocytopenia, or heart failure). Initiators of diclofenac were compared to healthcare-seeking non-initiators, but also head-to-head for initiators of high (≥75 mg pills as proxy for ≥150 mg/daily) vs. low dose (≤50 mg pills as proxy for <150 mg/daily). Cox proportional-hazards re