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

W G Dixon, K D Watson, M Lunt, K L Hyrich, British Society for Rheumatology Biologics Register Control Centre Consortium, A J Silman, D P M Symmons, British Society for Rheumatology Biologics Register, W G Dixon, K D Watson, M Lunt, K L Hyrich, British Society for Rheumatology Biologics Register Control Centre Consortium, A J Silman, D P M Symmons, British Society for Rheumatology Biologics Register

Abstract

Objective: Rheumatoid arthritis (RA) is associated with an increased risk of coronary artery disease, possibly acting via shared mechanisms of inflammation. This study was undertaken to test the hypothesis that the powerful antiinflammatory effect of anti-tumor necrosis alpha (anti-TNFalpha) therapy might lead to a reduction in the incidence of myocardial infarction (MI) in patients with RA.

Methods: Using data from the British Society for Rheumatology Biologics Register, a national prospective observational study, we compared MI rates in 8,670 patients with RA treated with anti-TNFalpha and 2,170 patients with active RA treated with traditional disease-modifying antirheumatic drugs (DMARDs).

Results: Through July 2006, 63 MIs occurred in the anti-TNFalpha cohort during 13,233 person-years of followup and 17 MIs occurred in the DMARD cohort during 2,893 person-years of followup, equivalent to a rate of 4.8 events per 1,000 person-years and 5.9 events per 1,000 person-years, respectively. After adjustment for baseline risk factors, there was no reduction in the rate of MI in the anti-TNFalpha cohort compared with the DMARD cohort (incidence rate ratio 1.44 [95% confidence interval 0.56-3.67]). In an analysis of anti-TNFalpha-treated patients who responded to the treatment within 6 months versus those who did not, MI rates were found to be 3.5 events per 1,000 person-years in responders and 9.4 events per 1,000 person-years in nonresponders. The adjusted incidence rate ratio (95% confidence interval) for responders compared with nonresponders was 0.36 (0.19-0.69).

Conclusion: These results indicate that RA patients treated with anti-TNFalpha do not have a lower incidence of MI compared with RA patients treated with traditional DMARDs. However, the risk of MI is markedly reduced in those who respond to anti-TNFalpha therapy by 6 months compared with nonresponders. This finding supports the notion that inflammation plays a pivotal role in MI.

References

    1. Goodson NJ, Wiles NJ, Lunt M, Barrett EM, Silman AJ, Symmons DP. Mortality in early inflammatory polyarthritis: cardiovascular mortality is increased in seropositive patients. Arthritis Rheum. 2002;46:2010–9.
    1. Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005;52:402–11.
    1. Wolfe F, Freundlich B, Straus WL. Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. J Rheumatol. 2003;30:36–40.
    1. Symmons DP, Jones MA, Scott DL, Prior P. Longterm mortality outcome in patients with rheumatoid arthritis: early presenters continue to do well. J Rheumatol. 1998;25:1072–7.
    1. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003;107:1303–7.
    1. Del Rincon ID, Williams K, Stern MP, Freeman GL, Escalante A. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001;44:2737–45.
    1. Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ. 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. Arthritis Rheum. 2005;52:2293–9.
    1. Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum. 2005;52:722–32.
    1. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–95.
    1. Feldmann M, Brennan FM, Williams RO, Woody JN, Maini RN. The transfer of a laboratory based hypothesis to a clinically useful therapy: the development of anti-TNF therapy of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2004;18:59–80.
    1. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti–tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003;48:35–45.
    1. Moreland LW, Schiff MH, Baumgartner SW, Tindall EA, Fleischmann RM, Bulpitt KJ, et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med. 1999;130:478–86.
    1. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, et al. the ATTRACT Study Group. Infliximab (chimeric anti-tumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet. 1999;354:1932–9.
    1. Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation. 2003;108:2957–63.
    1. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–874.
    1. Carter AM. Inflammation, thrombosis and acute coronary syndromes. Diab Vasc Dis Res. 2005;2:113–21.
    1. Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica. 2000;85:967–72.
    1. Jacobsson LT, Turesson C, Gulfe A, Kapetanovic MC, Petersson IF, Saxne T, et al. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol. 2005;32:1213–8.
    1. Watson K, Symmons D, Griffiths I, Silman A. The British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2005;64(Suppl 4):iv42–3.
    1. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight–joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44–8.
    1. Ledingham J, Deighton C. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001) [published erratum appears in Rheumatology (Oxford) 2006;45:1170] Rheumatology (Oxford) 2005;44:157–63. on behalf of the British Society for Rheumatology Standards, Guidelines and Audit Working Group (SGAWG)
    1. National Institute for Clinical Excellence. 2002. Guidance on the use of etanercept and infliximab for the treatment of rheumatoid arthritis. URL: .
    1. Kirwan JR, Reeback JS. Stanford Health Assessment Questionnaire modified to assess disability in British patients with rheumatoid arthritis. Br J Rheumatol. 1986;25:206–9.
    1. Townsend P. Deprivation. J Soc Policy. 1987;16:125–46.
    1. Geneva: World Health Organization; 1992. International statistical classification of diseases and related health problems, tenth revision.
    1. Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J. 2000;21:1502–13.
    1. Van Gestel AM, Prevoo ML, van 't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis: comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism criteria. Arthritis Rheum. 1996;39:34–40.
    1. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990;323:236–41.
    1. Rauchhaus M, Doehner W, Francis DP, Davos C, Kemp M, Liebenthal C, et al. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation. 2000;102:3060–7.
    1. Anker SD, Coats AJ. How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol. 2002;86:123–30.
    1. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT for the ATTACH Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-α, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107:3133–40.
    1. Kurrelmeyer KM, Michael LH, Baumgarten G, Taffet GE, Peschon JJ, Sivasubramanian N, et al. Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction. Proc Natl Acad Sci U S A. 2000;97:5456–61.
    1. Mann DL. Stress-activated cytokines and the heart: from adaptation to maladaptation. Annu Rev Physiol. 2003;65:81–101.
    1. Shah PK. Insights into the molecular mechanisms of plaque rupture and thrombosis. Indian Heart J. 2005;57:21–30.
    1. Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, Tolonen H, Ruokokoski E, Amouyel P. Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease. Lancet. 1999;353:1547–57.
    1. Watson DJ, Rhodes T, Guess HA. All-cause mortality and vascular events among patients with rheumatoid arthritis, osteoarthritis, or no arthritis in the UK General Practice Research Database. J Rheumatol. 2003;30:1196–202.

Source: PubMed

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