Subgroup analysis evaluating the incidence rate and hazard ratio of composite CVD events and each component associated with MTX use, restricted to patients exposed to MTX at any time before initiation of biologic DMARDs.
| MTXa Exposed | MTXa Unexposed | Unadjusted HR (95% CI) | Adjusted HRb (95% CI) | |||
|---|---|---|---|---|---|---|
| Event (PY) | IR (95% CI) | Event (PY) | IR (95% CI) | |||
| MI, stroke, or fatal CVD | 518 | 12.1 | 791 | 16.8 | 0.72 | 0.76 |
| 42,981 | (11.0–13.1) | 47,132 | (15.6–18.0) | (0.64–0.80) | (0.67–0.85) | |
| MI | 276 | 6.4 | 416 | 8.8 | 0.73 | 0.75 |
| 43,163 | (5.7–7.2) | 47,387 | (8.0–9.7) | (0.62–0.85) | (0.64–0.89) | |
| Stroke | 233 | 5.4 | 364 | 7.7 | 0.71 | 0.75 |
| 43,213 | (4.7–6.1) | 47,526 | (6.9–8.5) | (0.60–0.83) | (0.63–0.90) | |
| MI or stroke | 494 | 11.5 | 750 | 15.9 | 0.72 | 0.76 |
| 42,981 | (10.5–12.6) | 47,132 | (14.8–17.1) | (0.65–0.81) | (0.67–0.86) | |
| MI, stroke, angina, PCI, | 494 | 14.3 | 627 | 17.3 | 0.83 | 0.81 |
| CABG, or fatal CVD | 34,430 | (13.1–15.7) | 36,305 | (16.0–18.7) | (0.74–0.94) | (0.71–0.92) |
↵aTime-varying MTX was defined as days of supply with no extension.
↵bAdjusted for age, sex, race, Charlson Comorbidity Index, biologic DMARDs initiated, baseline MTX, hydroxychloroquine, leflunomide, sulfasalazine, heart failure, atrial fibrillation, abdominal aortic aneurism, peripheral arterial disease, diabetes, hyperlipidemia, hypertension, obesity, chronic kidney disease, chronic obstructive pulmonary disease, fibromyalgia, any hospitalized infection, any hospitalization, number of physician visits, folic acid, nonsteroidal antiinflammatory drugs, statin potency, other lipid-lowering drug use at baseline, number of biologics used prior initiation, oral steroid dose in 6 months before initiation, smoking, state buy-in (poor), Medicare eligibility for reasons other than age, time-varying folic acid (defined as days of supply with no extension), and nonalcoholic fatty liver disease and metabolic syndrome (defined using diagnosis codes in both baseline and follow-up periods).
CABG: coronary artery bypass grafting; CVD: cardiovascular disease; HR: hazard ratio; IR: incidence rate; DMARD: disease-modifying antirheumatic drug; MI: myocardial infarction; MTX: methotrexate; PCI: percutaneous coronary intervention; PY: person-years.