Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.
Accelerated atherosclerosis and cardiovascular disease are two chief causes of mortality associated with RA. The drug has anti-inflammatory properties, and recent data show that it may have additional beneficial effects on cardiovascular risk factors by lowering LDL cholesterol levels. The drug may reduce the risk for diabetes and improving the elasticity of atherosclerotic arteries.
Researchers in Israel set out to determine if hydroxychloroquine had an independent beneficial effect on cardiovascular morbidity in RA patients. They conducted a retrospective cohort study of 514 participants diagnosed with RA who were 18 or older at the time of diagnosis and had been treated at the researchers’ medical center between 2003 and 2013.
“Cardiovascular morbidity and mortality pose a substantial burden on the lives of our RA patients, with limited tools to address this aspect of the disease. Our clinical practice as well as the aforementioned research led us to believe that hydroxychloroquine might harbor a protective effect against cardiovascular disease,” said Michael Shapiro, MD of Meir Medical Center in Kfar Saba, Israel and a lead author of the study. “However, no previous trials provided concrete evidence to support our impression. We decided to conduct a study focused on the effect of hydroxychloroquine, with the hope to contribute to clinical decision making.”
Patients were divided into two groups –241 patients who had been treated with hydroxychloroquine during the course of their disease and 273 patients who had never received the drug. Possible confounding factors, including parameters of disease severity, common cardiovascular risk factors and additional medications, were considered. The researchers measured cardiovascular events experienced by the participants, including: myocardial infarction, stroke, transient ischemic attack, mesenteric event, pulmonary embolism and peripheral venous thrombosis.
The researchers found that 13.3 percent of the patients treated with hydroxychloroquine suffered from cardiovascular events compared to 38.1 percent of those patients who were not treated with the drug. In addition, the study showed that a higher dose of 400 mg per day versus 200 mg day provided even more protection from cardiovascular events. The 400 mg dose had a statistically significant protective effect for myocardial infarction, stroke and transient ischemic attack and venous thrombosis. A lower dose of 200 mg per day demonstrated a protective effect for myocardial infarction, but had no significant effect on other endpoints in the study.
The study’s authors concluded that treatment with hydroxychloroquine, particularly at 400 mg per day doses, offers significant, independent protection against cardiovascular morbidity for people with RA, and that the drug should be considered in the overall management of this disease.
“RA patients have a two-fold increased risk of cardiovascular events compared to the general population. Prevention is thus of utmost importance,” said Dr. Shapiro. “Our study provides novel evidence that hydroxychloroquine contributes to the prevention of cardiovascular morbidity among RA patients. Therefore, we believe that in clinical decision making, hydroxychloroquine should be considered not only for its anti-inflammatory effects but also for the drug’s added preventative value.”
The study was funded independently.
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Paper Number: 1846
The Association Between Hydroxychloroquine Treatment and Cardiovascular Morbidity Among Rheumatoid Arthritis Patients
Michael Shapiro1 and Yair Levy2, 1Haim Lebanon 55, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 2Internal Medicine E, Meir Medical Center, Kfar Saba, Israel
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.
Disclosure: M. Shapiro, None; Y. Levy, None.
Meeting Link: American College of Rheumatology Annual Meeting
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