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Background  Cardiovascular disease ( CVD ) is the leading cause of death in rheumatoid arthritis ( RA ) patients. This study is the first to report the association of hydroxychloroquine (an antirheumatic medication that has been associated with decreased risk of diabetes, a less atherogenic lipid profile, and antithrombotic properties) with  CVD  in  RA .    Methods and Results  A retrospective incident  RA  cohort from January 1, 2001, to October 31, 2013, excluding patients with  CVD  prior to  RA  diagnosis, was constructed. Patients were categorized as hydroxychloroquine users versus nonusers and were allowed to contribute time to either group according to hydroxychloroquine exposure. The primary outcome was adjudicated incident  CVD  defined as a composite of coronary artery disease, stroke, transient ischemic attack, sudden cardiac death, and peripheral artery disease with arterial revascularization procedure. The secondary outcome was a composite of incident coronary artery disease, stroke, and transient ischemic attack. Cox time‐varying regression models were used to estimate the association between hydroxychloroquine exposure and development of  CVD,  after adjusting for propensity score and relevant confounders, including demographics,  CVD ‐related comorbidities,  RA  severity, and activity indicators and medications. We included 1266  RA  patients, 547 hydroxychloroquine users, and 719 nonusers. During the observation period, 102  CVD  events occurred, 3 in hydroxychloroquine users and 99 in nonusers. The fully adjusted Cox model showed a hazard ratio of 0.28 (95% CI 0.12–0.63,  P =0.002) for incident  CVD  and 0.30 (95% CI 0.13–0.68,  P =0.004) for incident composite coronary artery disease, stroke, and transient ischemic attack for hydroxychloroquine users versus nonusers, respectively.    Conclusion  In this hypothesis‐generating study, hydroxychloroquine use was associated with a 72% decrease in the risk of incident  CVD  in  RA  patients. If these preliminary results are confirmed in larger studies, our findings may be used as a rationale for a randomized study of hydroxychloroquine use for primary prevention of  CVD  in  RA  or nonrheumatic high‐risk patients.

Hydroxychloroquine Use Is Associated With Decreased Incident Cardiovascular Events in Rheumatoid Arthritis Patients