Electronic Thesis and Dissertation Repository


Master of Science


Epidemiology and Biostatistics


Dr. Daniel Hackam


We conducted a systematic review and meta-analysis to assess the association of MTX with cardiovascular morbidity, cardiovascular mortality and all-cause mortality in patients with autoimmune disease. Our primary outcome was incident cardiovascular events. After screening 13,479 citations, we identified a total of 30 eligible studies. We synthesized adjusted risk estimates using a random effects model. MTX was significantly associated with a 25% reduction in cardiovascular events (pooled RR: 0.75, 95% CI: 0.65, 0.86, I2: 11%), a 55% reduction in cardiovascular mortality (0.45, 95% CI: 0.26, 0.80, I2: 33%) and a 40% reduction in all-cause mortality (0.60, 95% CI: 0.48, 0.76, I2: 45%). Low-dose MTX was associated with a stronger effect size for reducing cardiovascular events compared to high-dose MTX (0.61, 95% CI: 0.51, 0.74 versus 0.88, 95% CI: 0.78, 0.99). We concluded a significant associative reduction in cardiovascular events with the use of low-dose MTX in patients with autoimmune disease.