Methotrexate might reduce ischemic stroke in patients with rheumatoid arthritis

Aim: To investigate the effects of hydroxychloroquine, sulfasalazine and methotrexate on ischemic stroke in patients with rheumatoid arthritis (RA). Methods: This population-based retrospective cohort study included 7904 RA patients and 15 808 non-RA patients between 2000 and 2010. All of the participants were sampled from the National Health Insurance Research Database (NHIRD) of Taiwan. Using univariate analyses, these two groups of patients were compared to evaluate the differences in disease-modifying anti-rheumatic drugs usage and demographic variables. Cox proportional hazard models and Schoenfeld residuals test were performed to estimate the hazard ratios for ischemic stroke and proportional hazard assumptions of these drugs, respectively. Results: The mean age of participants was about 53 years old, and about 70% of RA patients were women. The hazard ratio for ischemic stroke was 1.21 (95% CI: 1.10–1.34; P < 0.01) in the case group compared with the control group, and this significant difference persisted throughout the 10-year period. With respect to RA patients, while hydroxychloroquine showed an insignificant protective effect on ischemic stroke, sulfasalazine and methotrexate were found out to have inconsistent effects during these 10 years. The proportional hazard assumption test of methotrexate at > 0.5 defined daily dose (8.75 mg/week) was violated at a significant level after adjustment (P = 0.0002). Conclusions: At a dosage of > 0.5 defined daily dose, short-term methotrexate might decrease ischemic stroke risk in RA patients, while hydroxychloroquine and sulfasalazine were neutral.