title: Hydroxychloroquine Use Is Associated With Decreased Incident Cardiovascular Events in Rheumatoid Arthritis Patients.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Rheumatology Department, Geisinger Medical Center, Danville, PA (T.S.S., A.B.) Rheumatology Department, West Penn Allegheny Health System, Pittsburgh, PA (T.S.S., M.C.M.W., X.T.).
authors.forename: Tarun S
authors.initials: TS
authors.lastname: Sharma
authors.affiliation: Rheumatology Department, West Penn Allegheny Health System, Pittsburgh, PA (T.S.S., M.C.M.W., X.T.).
authors.forename: Mary Chester M
authors.initials: MC
authors.lastname: Wasko
authors.affiliation: Rheumatology Department, West Penn Allegheny Health System, Pittsburgh, PA (T.S.S., M.C.M.W., X.T.) Biostatistics Department, Center for Health Research, Danville, PA (X.T., X.Y.).
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Hospital Medicine Department, Geisinger Medical Center, Danville, PA (D.V.).
authors.forename: Deepak
authors.initials: D
authors.lastname: Vedamurthy
authors.affiliation: Biostatistics Department, Center for Health Research, Danville, PA (X.T., X.Y.) Sutter Health, Sacramento, CA (X.Y.).
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yan
authors.affiliation: Rheumatology Department, Geisinger Wyoming Valley, Wilkes-Barre, PA (J.C.).
authors.forename: Jonida
authors.initials: J
authors.lastname: Cote
authors.affiliation: Rheumatology Department, Geisinger Medical Center, Danville, PA (T.S.S., A.B.).
authors.forename: Androniki
authors.initials: A
authors.lastname: Bili
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D015897:Comorbidity; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010414:Pennsylvania / Q000453:epidemiology; D057216:Propensity Score; D016016:Proportional Hazards Models; D065840:Protective Factors; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine
keywords: cardiovascular diseases; hydroxychloroquine; primary prevention; rheumatoid arthritis