Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis
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 enr...
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Published in | Annals of the rheumatic diseases Vol. 70; no. 4; pp. 576 - 582 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group Ltd and European League Against Rheumatism
01.04.2011
BMJ Publishing Group BMJ Publishing Group LTD |
Subjects | |
Online Access | Get full text |
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Abstract | 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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AbstractList | 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. 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). 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. 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). TNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA. 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. OBJECTIVETo 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). METHODSThe 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. RESULTSThere 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). CONCLUSIONTNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA. |
Author | Kremer, Joel M Setoguchi, Soko Solomon, Daniel H Curtis, Jeffrey R Nasir, Adeel Tsao, Peter Reed, George Farkouh, Michael E Hochberg, Marc C Greenberg, Jeffrey D |
Author_xml | – sequence: 1 givenname: Jeffrey D surname: Greenberg fullname: Greenberg, Jeffrey D email: jeffrey.greenberg@nyumc.org organization: Department of Rheumatology, New York University Hospital for Joint Diseases, New York, New York, USA – sequence: 2 givenname: Joel M surname: Kremer fullname: Kremer, Joel M email: jeffrey.greenberg@nyumc.org organization: Division of Rheumatology, Albany Medical College, Albany, New York, USA – sequence: 3 givenname: Jeffrey R surname: Curtis fullname: Curtis, Jeffrey R email: jeffrey.greenberg@nyumc.org organization: Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA – sequence: 4 givenname: Marc C surname: Hochberg fullname: Hochberg, Marc C email: jeffrey.greenberg@nyumc.org organization: Division of Rheumatology and Clinical Immunology, University of Maryland, Baltimore, Maryland, USA – sequence: 5 givenname: George surname: Reed fullname: Reed, George email: jeffrey.greenberg@nyumc.org organization: Division of Preventive and Behavioral Medicine, University of Massachusetts School of Medicine, Worcester, Massachusetts, USA – sequence: 6 givenname: Peter surname: Tsao fullname: Tsao, Peter email: jeffrey.greenberg@nyumc.org organization: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA – sequence: 7 givenname: Michael E surname: Farkouh fullname: Farkouh, Michael E email: jeffrey.greenberg@nyumc.org organization: Clinical Trials Unit, Mount Sinai Heart, New York, New York, USA – sequence: 8 givenname: Adeel surname: Nasir fullname: Nasir, Adeel email: jeffrey.greenberg@nyumc.org organization: Department of Rheumatology, New York University Hospital for Joint Diseases, New York, New York, USA – sequence: 9 givenname: Soko surname: Setoguchi fullname: Setoguchi, Soko email: jeffrey.greenberg@nyumc.org organization: Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, Massachusetts, USA – sequence: 10 givenname: Daniel H surname: Solomon fullname: Solomon, Daniel H email: jeffrey.greenberg@nyumc.org organization: Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, Massachusetts, USA |
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ContentType | Journal Article |
Copyright | Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions 2015 INIST-CNRS Copyright: 2011 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions |
Copyright_xml | – notice: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions – notice: 2015 INIST-CNRS – notice: Copyright: 2011 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions |
CorporateAuthor | CORRONA Investigators |
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Keywords | Human Immunopathology Chronic Tumor necrosis factor Rheumatoid arthritis Diseases of the osteoarticular system Risk factor Rheumatology Autoimmune disease Inflammatory joint disease Antagonist |
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References | Solomon, Avorn, Katz 2006; 54 Gartlehner, Hansen, Jonas 2006; 33 Dixon, Symmons 2007; 66 del Rincón, Williams, Stern 2001; 44 Felson, Anderson, Boers 1995; 38 Dixon, Watson, Lunt 2007; 56 Gonzalez-Gay, De Matias, Gonzalez-Juanatey 2006; 24 Goodson, Symmons, Scott 2005; 52 Barath, Fishbein, Cao 1990; 65 Solomon, Karlson, Rimm 2003; 107 Popa, Netea, Radstake 2005; 64 Ridker, Rifai, Pfeffer 2000; 101 Farkouh, Kirshner, Harrington 2004; 364 Carmona, Descalzo, Perez-Pampin 2007; 66 Prevoo, van‘t Hof, Kuper 1995; 38 Ridker, Hennekens, Buring 2000; 342 Suissa, Bernatsky, Hudson 2006; 55 Herskowitz, Choi, Ansari 1995; 146 Hochberg, Lebwohl, Plevy 2005; 34 Choi, Hernán, Seeger 2002; 359 Feldmann, Maini 2001; 19 Tam, Tomlinson, Chu 2007; 26 Van Doornum, McColl, Wicks 2002; 46 Pincus, Summey, Soraci, Jr 1983; 26 Gonzalez-Juanatey, Testa, Garcia-Castelo 2004; 51 Del Rincón, Williams, Stern 2003; 48 Ridker, Rifai, Stampfer 2000; 101 Wolfe, Michaud 2008; 58 Kremer 2005; 64 Hürlimann, Forster, Noll 2002; 106 Jacobsson, Turesson, Gülfe 2005; 32 Davis, Maradit Kremers, Crowson 2007; 56 Ross 1999; 340 Mäki-Petäjä, Hall, Booth 2006; 114 Solomon, Goodson, Katz 2006; 65 Del Porto, Laganà, Lai 2007; 46 Maradit-Kremers, Nicola, Crowson 2005; 52 Kremer 2005; 23 21372192 - Ann Rheum Dis. 2011 Apr;70(4):561-2 |
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A review of the role of TNFalpha in cardiovascular pathophysiology publication-title: Ann Rheum Dis contributor: fullname: Symmons – volume: 55 start-page: 531 year: 2006 article-title: Antirheumatic drug use and the risk of acute myocardial infarction publication-title: Arthritis Rheum contributor: fullname: Hudson – volume: 44 start-page: 2737 year: 2001 article-title: High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors publication-title: Arthritis Rheum contributor: fullname: Stern – volume: 106 start-page: 2184 year: 2002 article-title: Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis publication-title: Circulation contributor: fullname: Noll – volume: 58 start-page: 2612 year: 2008 article-title: The risk of myocardial infarction and pharmacologic and nonpharmacologic myocardial infarction predictors in rheumatoid arthritis: a cohort and nested case-control analysis publication-title: Arthritis Rheum contributor: fullname: Michaud – volume: 56 start-page: 2905 year: 2007 article-title: Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register publication-title: Arthritis Rheum contributor: fullname: Lunt – volume: 54 start-page: 3790 year: 2006 article-title: Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis publication-title: Arthritis Rheum contributor: fullname: Katz – volume: 32 start-page: 1213 year: 2005 article-title: Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis publication-title: J Rheumatol contributor: fullname: Gülfe – volume: 364 start-page: 675 year: 2004 article-title: Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial publication-title: Lancet contributor: fullname: Harrington – volume: 107 start-page: 1303 year: 2003 article-title: Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis publication-title: Circulation contributor: fullname: Rimm – volume: 34 start-page: 819 year: 2005 article-title: The benefit/risk profile of TNF-blocking agents: findings of a consensus panel publication-title: Semin Arthritis Rheum contributor: fullname: Plevy – volume: 66 start-page: 880 year: 2007 article-title: All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists publication-title: Ann Rheum Dis contributor: fullname: Perez-Pampin – volume: 64 start-page: iv37 year: 2005 article-title: The CORRONA database 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cardiovascular risk factors in patients with active rheumatoid arthritis publication-title: Ann Rheum Dis contributor: fullname: Radstake – volume: 52 start-page: 2293 year: 2005 article-title: Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort publication-title: Arthritis Rheum contributor: fullname: Scott – volume: 26 start-page: 1495 year: 2007 article-title: Impact of TNF inhibition on insulin resistance and lipids levels in patients with rheumatoid arthritis publication-title: Clin Rheumatol contributor: fullname: Chu – volume: 56 start-page: 820 year: 2007 article-title: Glucocorticoids and cardiovascular events in rheumatoid arthritis: a population-based cohort study publication-title: Arthritis Rheum contributor: fullname: Crowson – volume: 342 start-page: 836 year: 2000 article-title: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women publication-title: N Engl J Med contributor: fullname: Buring – volume: 101 start-page: 1767 year: 2000 article-title: Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men publication-title: Circulation contributor: fullname: Stampfer – volume: 52 start-page: 722 year: 2005 article-title: Cardiovascular death in rheumatoid arthritis: a population-based study publication-title: Arthritis Rheum contributor: fullname: Crowson – volume: 48 start-page: 1833 year: 2003 article-title: Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects publication-title: Arthritis Rheum contributor: fullname: Stern – volume: 24 start-page: 83 year: 2006 article-title: Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis publication-title: Clin Exp Rheumatol contributor: fullname: Gonzalez-Juanatey – volume: 46 start-page: 1111 year: 2007 article-title: Response to anti-tumour necrosis factor alpha blockade is associated with reduction of carotid intima-media thickness in patients with active rheumatoid arthritis publication-title: Rheumatology (Oxford) contributor: fullname: Lai – volume: 19 start-page: 163 year: 2001 article-title: Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? publication-title: Annu Rev Immunol contributor: fullname: Maini – volume: 114 start-page: 1185 year: 2006 article-title: Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-alpha therapy publication-title: Circulation contributor: fullname: Booth – volume: 26 start-page: 1346 year: 1983 article-title: Assessment of patient satisfaction in activities of daily living using a modified Stanford Health Assessment Questionnaire publication-title: Arthritis Rheum contributor: 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Preliminary definition of improvement in rheumatoid arthritis publication-title: Arthritis Rheum contributor: fullname: Boers – volume: 340 start-page: 115 year: 1999 article-title: Atherosclerosis – an inflammatory disease publication-title: N Engl J Med contributor: fullname: Ross – volume: 51 start-page: 447 year: 2004 article-title: Active but transient improvement of endothelial function in rheumatoid arthritis patients undergoing long-term treatment with anti-tumor necrosis factor alpha antibody publication-title: Arthritis Rheum contributor: fullname: Garcia-Castelo – volume: 65 start-page: 297 year: 1990 article-title: Detection and localization of tumor necrosis factor in human atheroma publication-title: Am J Cardiol contributor: fullname: Cao – volume: 359 start-page: 1173 year: 2002 article-title: Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study publication-title: Lancet contributor: fullname: Seeger |
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SubjectTerms | Adult Aged Antirheumatic Agents - therapeutic use Arthritis, Rheumatoid - complications Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - epidemiology Biological and medical sciences Cardiovascular Diseases - epidemiology Cardiovascular Diseases - etiology Cardiovascular Diseases - prevention & control Diseases of the osteoarticular system Epidemiologic Methods Female Health risk assessment Heart attacks Humans Immunologic Factors - therapeutic use Inflammatory joint diseases Male Medical sciences Middle Aged Studies Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor necrosis factor-TNF United States - epidemiology |
Title | Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis |
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