Rheumatoid arthritis (RA) is associated with increased mortality and morbidity due to atherosclerotic coronary artery disease (CAD) that cannot be attributed to traditional cardiovascular risk factors alone. 1 A method for risk adjustment in patients with RA has been proposed by the European League Against Rheumatism (EULAR) expert panel—which suggested multiplying commonly used risk calculators, such as the Systematic Coronary Risk Evaluation (SCORE) method or the Framingham risk model (often used in the United States)—by a factor of 1.5 in patients with RA who satisfy at least 2 of 3 criteria.2 These criteria include having RA for longer than 10 years, anti-cyclic citrullinated peptide antibodies or rheumatoid factor, and having the presence of extraarticular manifestations of RA.
Observational data have suggested that early diagnosis and effective control of RA disease activity appears to reduce CVD risk. 3 Early treatment of joint inflammation with nonbiologic and biologic medication was believed to not only control synovitis but also decrease the systemic inflammatory state that may contribute to atherosclerosis. However, a subsequent study found that anti-tumor necrosis factor (anti-TNF) therapy conferred no protective effects against myocardial infarction (MI) in RA after adjusting for baseline risk.4
It was also later found that certain biologics like tocilizumab may increase levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C),5 and triglycerides; it is well established that high levels of LDL-C are a risk factor for CAD.6
To further investigate CAD risk associated with biologic treatment in RA, Zhang and colleagues conducted a retrospective observational cohort study of 47,194 Medicare patients who initiated treatment with a biologic disease-modifying antirheumatic drug (DMARD) and who were free of CAD at time of enrollment.7
Compared with patients who started treatment with abatacept, risk of acute MI was higher among patients who started treatment with an anti-TNF agent (adjusted hazard ratio [aHR] 1.3; 95% confidence interval [CI], 1.0-1.6), including etanercept (aHR 1.3; 95% CI, 1.0-1.8) and infliximab (aHR 1.3; 95% CI, 1.0-1.6). Patients who were started on treatment with tocilizumab were at reduced risk of the composite outcome compared with those starting treatment with abatacept (aHR 0.64; 95% CI, 0.41-0.99).
Summary and Clinical Applicability
Early diagnosis and initiation of DMARD treatment for RA reduces the potential future morbidity due to disease. Certain anti-TNF biologic drugs, while effective at treating synovitis, may confer an elevated risk of MI compared to other medications. This increased risk should be taken into consideration when selecting treatment regimens for patients with RA.
1. Maradit-Kremers H, Nicola PJ, Crowson CS, et al. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2005;52:722-732.
2. Peters MJ, Symmons DP, McCarey D, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010;69:325-331.
3. Crowson CS, Matteson EL, Roger VL, et al. Usefulness of risk scores to estimate the risk of cardiovascular disease in patients with rheumatoid arthritis. Am J Cardiol. 2012;110:420-424.
4. Dixon WG, Watson KD, Lunt M, et al. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 2007;56(9):2905-2912.
5. McInnes IB, Thompson L, Giles JT, et al. Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study. Ann Rheum Dis. 2015;74:694-702.
6. Wilson, Peter WF, et al. “Prediction of coronary heart disease using risk factor categories.” Circulation 97.18 (1998): 1837-1847.Zhang J, Xie F, Yun H, et al. Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis. Ann Rheum Dis. 2016; Jan 20. pii: annrheumdis-2015-207870. doi: 10.1136/annrheumdis-2015-207870. [Epub ahead of print]
7. Zhang J, Xie F, Yun H, et al. Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis. Ann Rheum Dis. 2016; Jan 20. pii: annrheumdis-2015-207870. doi: 10.1136/annrheumdis-2015-207870. [Epub ahead of print]