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The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis
  1. Camille Roubille1,
  2. Vincent Richer2,
  3. Tara Starnino3,
  4. Collette McCourt4,
  5. Alexandra McFarlane5,
  6. Patrick Fleming6,
  7. Stephanie Siu7,
  8. John Kraft8,
  9. Charles Lynde8,
  10. Janet Pope7,
  11. Wayne Gulliver9,
  12. Stephanie Keeling5,
  13. Jan Dutz4,
  14. Louis Bessette10,
  15. Robert Bissonnette11,
  16. Boulos Haraoui12
  1. 1University of Montreal Hospital Research Center (CRCHUM), Notre-Dame Hospital, Montreal, Quebec, Canada
  2. 2Department of Medicine, Dermatology Service, St-Luc Hospital, Montreal, Quebec, Canada
  3. 3Sacré-Coeur Hospital of Montreal, University of Montreal, Montreal, Quebec, Canada
  4. 4Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
  5. 5Division of Rheumatology, University of Alberta, Edmonton, Alberta, Canada
  6. 6Division of Dermatology, University of Toronto, Toronto, Ontario, Canada
  7. 7Division of Rheumatology, Department of Medicine, Western University of Canada, St. Joseph's Health Care, London, Ontario, Canada
  8. 8Lynde Dermatology, Markham, Ontario, Canada
  9. 9Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
  10. 10Department of Medicine, Centre de Recherche du CHU de Québec, Laval University, Quebec City, Quebec, Canada
  11. 11Innovaderm Research, Montreal, Quebec, Canada
  12. 12Department of Medicine, Rheumatic Disease Unit, Centre Hospitalier de l'Université de Montréal (CHUM) and Institut de Rhumatologie de Montréal, Montreal, Quebec, Canada
  1. Correspondence to Boulos Haraoui, Institut de Rhumatologie de Montreal, 1551 Ontario Street East, Montreal, Quebec, Canada H2L 1S6; boulos.haraoui{at}


The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso).

Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data.

Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003).

In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.

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