Can rheumatoid arthritis (RA) medications lower my risk for heart attack and stroke?

Individuals diagnosed with rheumatoid arthritis (RA) are at an increased risk of developing cardiovascular disease (CVD) compared to the general population.^1-3 RA disease activity can be quantified using various methods including a tender and swollen joint count, C-reactive protein (CRP), and a patient global assessment, which comprises a Simplified Disease Activity score. High disease activity, in conjunction with frequent and severe pain flares, contributes to the risk of CVD an RA patient may incur.^4-6

Medications that are used long-term to treat RA and target disease activity and inflammation have been shown to decrease the risk for CVD events like heart attacks and strokes in patients with RA.^7,8 Methotrexate, a csDMARD, and bDMARDs like tumor necrosis factor (TNF) inhibitors, are associated with significant reductions in CVD risk when used for RA treatment over time.^7-9 A meta-analysis including 236,525 RA patients showed a 30% and 28% decrease in the risk of CVD events when using TNF inhibitors or methotrexate to treat RA, respectively.⁸ The European League Against Rheumatism (EULAR) recommends reducing CVD risk in this population by controlling disease activity.⁷ The American College of Rheumatology (ACR) also recommends the use of csDMARDs and bDMARDs in patients with RA to help reduce disease activity and the risk of CVD events.¹⁰

Current research suggests that glucocorticoids, such as prednisone, have a dose-dependent relationship with CVD and are associated with an increased risk of CVD events in patients with RA. EULAR guidelines suggest to minimize use and dose of glucocorticoids, although the CVD-related effects of low-dose glucocorticoid use is less clear for patients persistently in low disease activity or remission.⁷ For instance, one study using administrative health data from 8,384 RA patients found that any current use of glucocorticoids (not taking into account duration or dose of glucocorticoid) was associated with a 68% increased risk of heart attack. The risk continued to rise per additional year on glucocorticoids and 13% per 5mg/day increase in the dose of glucocorticoids.¹¹ However, this effect may be confounded by RA disease activity¹⁴, even though the effect of corticosteroids on CVD events in patients with RA remained after controlling for disease activity.^12,13 

References

1. Radner H, Lesperance T, Accortt NA, Solomon DH. Incidence and prevalence of cardiovascular risk factors among patients with rheumatoid arthritis, psoriasis, or psoriatic arthritis. Arthritis care & research. 2017;69(10):1510-1518.
2. Mutru O, Laakso M, Isomäki H, Koota K. Ten year mortality and causes of death in patients with rheumatoid arthritis. Br Med J (Clin Res Ed). 1985;290(6484):1797-1799.
3. Jagpal A, Navarro-Millán I. Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of risk factors, cardiovascular risk assessment and treatment. BMC rheumatology. 2018;2(1):10.
4. Ajeganova S, Andersson ML, Frostegård J, Hafström I. Disease factors in early rheumatoid arthritis are associated with differential risks for cardiovascular events and mortality depending on age at onset: a 10-year observational cohort study. The Journal of rheumatology. 2013;40(12):1958-1966.
5. Arts EE, Fransen J, den Broeder AA, Popa CD, van Riel PL. The effect of disease duration and disease activity on the risk of cardiovascular disease in rheumatoid arthritis patients. Annals of the rheumatic diseases. 2015;74(6):998-1003.
6. Myasoedova E, Chandran A, Ilhan B, et al. The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease. Annals of the rheumatic diseases. 2016;75(3):560-565.
7. Agca R, Heslinga S, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Annals of the rheumatic diseases. 2017;76(1):17-28.
8. Roubille C, Richer V, Starnino T, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Annals of the rheumatic diseases. 2015;74(3):480-489.
9. Singh S, Fumery M, Singh AG, et al. Comparative Risk of Cardiovascular Events With Biologic and Synthetic Disease‐Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis: A Systematic Review and Meta‐Analysis. Arthritis care & research. 2020;72(4):561-576.
10. Singh JA, Saag KG, Bridges Jr SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis & rheumatology. 2016;68(1):1-26.
11. Aviña-Zubieta JA, Abrahamowicz M, De Vera MA, et al. Immediate and past cumulative effects of oral glucocorticoids on the risk of acute myocardial infarction in rheumatoid arthritis: a population-based study. Rheumatology. 2013;52(1):68-75.
12. Ajeganova S, Svensson B, Hafström I, Group BS. Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial. BMJ open. 2014;4(4).
13. Del Rincón I, Battafarano DF, Restrepo JF, Erikson JM, Escalante A. Glucocorticoid dose thresholds associated with all‐cause and cardiovascular mortality in rheumatoid arthritis. Arthritis & rheumatology. 2014;66(2):264-272.
14. van Sijl AM, Boers M, Voskuyl AE, Nurmohamed MT. Confounding by indication probably distorts the relationship between steroid use and cardiovascular disease in rheumatoid arthritis: results from a prospective cohort study. PLoS One. 2014;9(1):e87965.