Reduction in Osteoarthritis Risk After Treatment With Ticagrelor Compared to Clopidogrel: A Propensity Score-Matching Analysis

Objective Osteoarthritis (OA) is a common cause of joint pain and disability, and effective treatments are lacking. Extracellular adenosine has antiinflammatory effects and can prevent and treat OA in animal models. Ticagrelor and clopidogrel are both used in patients with coronary artery disease, but only ticagrelor increases extracellular adenosine levels. This study was undertaken to determine whether treatment with ticagrelor was associated with a lower risk of OA. Methods We conducted a 1:2 propensity score-matching analysis using data from 2011-2017 in the Optum Clinformatics Data Mart. Patients who had received either ticagrelor or clopidogrel for >= 90 days were included in our study, and patients with a prior diagnosis of OA or inflammatory arthritis were excluded. OA was identified using International Classification of Diseases codes. The primary outcome was the time to diagnosis of OA after treatment with ticagrelor versus clopidogrel. Results Our propensity score-matched cohort consisted of 7,007 ticagrelor-treated patients and 14,014 clopidogrel-treated patients, with a median number of days receiving treatment of 287 and 284, respectively. For both groups, the mean age was 64 years, and 73% of the patients were male. Multivariate Cox regression analysis estimated a hazard ratio for developing OA of 0.71 (95% confidence interval 0.64-0.79) (P< 0.001) after treatment with ticagrelor compared to clopidogrel. Conclusion Treatment with ticagrelor was associated with a 29% lower risk of developing OA compared to treatment with clopidogrel over 5 years of follow-up. We hypothesize that the reduction in OA seen in patients who received ticagrelor may in part be due to increased extracellular adenosine levels.