Cardiovascular Risk in Rheumatoid Arthritis: Comparing TNF-α Blockade with Nonbiologic DMARDs

• Published in: The American journal of medicine Vol. 126; no. 8; pp. 730.e9 - 730.e17
• Main Authors: Solomon, Daniel H., Curtis, Jeffrey R., Saag, Kenneth G., Lii, Joyce, Chen, Lang, Harrold, Leslie R., Herrinton, Lisa J., Graham, David J., Kowal, Mary K., Kuriya, Bindee, Liu, Liyan, Griffin, Marie R., Lewis, James D., Rassen, Jeremy A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2013
• Subjects: Adult; Aged; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - drug therapy; Cardiovascular disease; Cardiovascular Diseases - complications; Cardiovascular Diseases - prevention & control; Cohort Studies; Female; Humans; Internal Medicine; Kaplan-Meier Estimate; Male; Methotrexate - therapeutic use; Middle Aged; Myocardial Infarction - prevention & control; Myocardial Revascularization; Proportional Hazards Models; Retrospective Studies; Rheumatoid arthritis; Risk; Stroke - prevention & control; TNF-α blocking agents; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; TNF-α blocking agents; Cardiovascular disease; Rheumatoid arthritis
• ISSN: 0002-9343; 1555-7162; 1555-7162
• DOI: 10.1016/j.amjmed.2013.02.016

Elevated tumor necrosis factor (TNF)-α likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNF-α blocking agent versus a nonbiologic disease-modifying antirheumatic drug (nbDMARD). Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998 and 2007 who received methotrexate were eligible. Those who added a TNF-α blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular end point of myocardial infarction, stroke, or coronary re-vascularization after 6 months. We compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-α blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular end point were 3.05 (95% confidence interval [CI], 2.54-3.65) for nbDMARDs and 2.52 (95% CI, 2.12-2.98) for TNF-α blocking agents. The hazard ratio (HR) for the TNF-α blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95%, CI 0.62-1.04), while the HR for the as-treated analysis was 0.71 (95% CI, 0.52-0.97). The potential cardiovascular benefit of TNF-α blocking agents was strongest among individuals ≥65 years of age (HR 0.52; 95% CI, 0.34 -0.77; P for interaction = 0.075). Among subjects with rheumatoid arthritis, TNF-α blocking agents may be associated with a reduced risk of cardiovascular events compared with an nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis.