Background/Purpose: Accelerated atherosclerosis and cardiovascular disease are the main causes of mortality in Rheumatoid Arthritis (RA). The anti-malarial drug Hydroxychloroquine (HCQ) has long been used in the treatment of RA due to its anti-inflammatory properties. Recent studies have demonstrated that HCQ has additional beneficial effects on cardiovascular risk factors by lowering LDL levels, reducing the risk for diabetes and improving elasticity of atherosclerotic arteries. Our aim was to examine the independent effect of HCQ treatment on cardiovascular morbidity among RA patients.

Methods: We conducted a retrospective cohort study in the Meir Medical Center. Participants were diagnosed with RA, were 18 or older at the time of diagnosis and had been treated in the medical center between 2003 and 2013. Patients were divided into two groups, those who had been treated with HCQ during the course of their disease and those who had never received the drug. The two groups were compared in regard to possible confounding factors, including parameters of disease severity, common cardiovascular risk factors and additional medications. The endpoints of our study were arterial and venous events, including: Myocardial Infarction (MI), stroke, Transient Ischemic Attack (TIA), mesenteric event, Pulmonary Embolism (PE) and peripheral venous thrombosis. The two groups were compared using a multivariate logistic regression. 

Results: We identified 514 RA patients that adhered to our inclusion criteria, 241 patients had been treated with HCQ for an average duration of 5 years and 273 patients had never been treated with the drug. We found that 13.3% of the treated patients suffered from cardiovascular events compared to 38.1% in the non-treated group. HCQ treatment had a significant protective effect for all cardiovascular events examined (OR=0.271, 95%CI 0.159 to 0.462). When comparing for specific endpoints we found a difference regarding the dosage of HCQ. A dose of 400mg per day of HCQ had a statistically significant protective effect for MI (OR= 0.405, 95%CI 0.181 to 0.908), for stroke and TIA (OR= 0.352, 95%CI 0.130 to 0.955) and for venous events (OR= 0.159, 95%CI 0.045 to 0.562). The lower dose of 200 mg per day demonstrated a protective effect for MI (OR=0.194, 95%CI 0.055 to 0.686), and no significant effect on other endpoints.

Conclusion: The use of HCQ is independently associated with decreased risk for cardiovascular morbidity among RA patients, particularly when using the higher dose of 400 mg per day. This newly demonstrated effect of HCQ should be considered in the overall management of RA. 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-between-hydroxychloroquine-treatment-and-cardiovascular-morbidity-among-rheumatoid-arthritis-patients/