Association between nonsteroidal anti-inflammatory drug use and major adverse cardiovascular events in patients with end-stage renal disease: a population-based cohort study

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for patients with end-stage renal disease (ESRD) despite clinical guideline recommendations that the use of NSAIDs be avoided in this population. However, the relationship between NSAID use and adverse cardiovascular events remains unclear. Thus, this study investigated the association between NSAID use and major adverse cardiovascular events (MACEs) in patients with ESRD. Methods: We used the Taiwan National Health Insurance Research Database to conduct this population-based cohort study of patients with newly diagnosed ESRD requiring long-term dialysis between 1998 and 2012. Clinical outcomes were evaluated until the end of 2013. Time-dependent Cox regression models were used to investigate the association between NSAID use and MACEs in patients with ESRD. Results: Among 2349 patients with ESRD receiving dialysis, 1923 (82%) patients used NSAIDs during the follow-up period. Multivariable analysis revealed that compared with nonusers, NSAID users exhibited an increased risk of MACEs with an adjusted hazard ratio (HR) of 1.70 (95% confidence interval [CI] 1.22–2.36). Further analysis demonstrated a significant dose–response relationship between the cumulative use of NSAIDs and MACEs. Adjusted HRs for MACEs were 1.63 (95% CI 1.16–2.30), 1.86 (95% CI 1.22–2.83), and 1.99 (95% CI 1.24–3.20) for cumulative NSAID use of 1–30 defined daily doses (DDDs), 31–90 DDDs, and > 90 DDDs, respectively. Conclusions: The results of this study suggest that NSAID use may increase the risk of MACEs in patients with ESRD. Clinicians and patients with ESRD should be aware of the potential cardiovascular risks associated with NSAIDs.