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Extended report
Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis
  1. Jeffrey D Greenberg1,
  2. Joel M Kremer2,
  3. Jeffrey R Curtis3,
  4. Marc C Hochberg4,
  5. George Reed5,
  6. Peter Tsao6,
  7. Michael E Farkouh7,
  8. Adeel Nasir1,
  9. Soko Setoguchi8,
  10. Daniel H Solomon8
  11. on behalf of the CORRONA Investigators
  1. 1Department of Rheumatology, New York University Hospital for Joint Diseases, New York, New York, USA
  2. 2Division of Rheumatology, Albany Medical College, Albany, New York, USA
  3. 3Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  4. 4Division of Rheumatology and Clinical Immunology, University of Maryland, Baltimore, Maryland, USA
  5. 5Division of Preventive and Behavioral Medicine, University of Massachusetts School of Medicine, Worcester, Massachusetts, USA
  6. 6Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA
  7. 7Clinical Trials Unit, Mount Sinai Heart, New York, New York, USA
  8. 8Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Jeffrey D Greenberg, Department of Rheumatology, New York University Hospital for Joint Diseases, 301 East 17th Street, Suite 1410, New York, NY 10003, USA; jeffrey.greenberg{at}


Objective To examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA).

Methods The study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death.

Results There were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74).

Conclusion TNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA.

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  • See Editorial, p561

  • Funding The study design, data analysis and reporting of results in this manuscript were performed independent of all funding sources. This work was funded by an Arthritis Clinical Translational Research Award in Rheumatoid Arthritis from the Arthritis Foundation (JDG). In the past 2 years, CORRONA has received general support from Abbott, Amgen, BMS, Centocor, Genentech, Lilly and Roche. Amgen and Centocor had supported an earlier project that was presented as an abstract at the 2006 Annual Scientific Meeting of the American College of Rheumatology, 13 November 2006 in Washington, DC, USA.

  • Competing interests JDG receives salary support from research grants from the National Institutes of Health (NIH) (K23AR054412), the Arthritis Foundation and Bristol Myers Squibb, he serves as chief scientific officer for CORRONA and has served on advisory boards for BMS, Centocor, Genentech, Roche and UCB. JRC receives salary support from NIH (AR053351) and the Agency for Healthcare Research and Quality (AHRQ) (R01HS018517) and research/consulting support from Genentech/Roche, Amgen, UCB, Centocor and BMS. DHS receives salary support from research grants from the NIH (AR055989 and AR047782), AHRQ, the Arthritis Foundation, Abbott and Amgen. GR has a research contract with CORRONA. Research support has been provided to JMK by Amgen, Abbott, Centocor, BMS, Roche and Genentech as well as honoraria from Abbott, Centocor, BMS, Roche and Genentech. MCH served as a consultant for Amgen, Bristol Meyers Squibb, Roche and UCB. PT, AN and MEF have declared no competing interests.

  • Patient consent Obtained.

  • Ethics approval This study was approved by the institutional review boards of participating academic sites and a central institutional review board for community-based private sites.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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