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Meta-Analysis
. 2015 Mar;74(3):480-9.
doi: 10.1136/annrheumdis-2014-206624. Epub 2015 Jan 5.

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

Camille Roubille  1 , Vincent Richer  2 , Tara Starnino  3 , Collette McCourt  4 , Alexandra McFarlane  5 , Patrick Fleming  6 , Stephanie Siu  7 , John Kraft  8 , Charles Lynde  8 , Janet Pope  7 , Wayne Gulliver  9 , Stephanie Keeling  5 , Jan Dutz  4 , Louis Bessette  10 , Robert Bissonnette  11 , Boulos Haraoui  12
Affiliations
Meta-Analysis

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

Camille Roubille et al. Ann Rheum Dis. 2015 Mar.

Abstract

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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Figures

Figure 1
Figure 1
Search and selection of studies for systematic review and meta-analysis. PsA, psoriatic arthritis; Pso, psoriasis; RA, rheumatoid arthritis.
Figure 2
Figure 2
Meta-analyses of all cardiovascular events and individual cardiovascular events in patients with rheumatoid arthritis treated with (A) tumour necrosis factor inhibitors; (B) methotrexate; (C) non-steroidal anti-inflammatory drugs; or (D) corticosteroids in controlled studies. Size of data markers indicates relative weight of the study (from random-effects analysis). COX-2, cyclooxygenase-2; CVE, cardiovascular event; MACE, major adverse cardiac event; MTX, methotrexate; RR, relative risk; TNFi, tumour necrosis factor inhibitor.
Figure 2
Figure 2
Meta-analyses of all cardiovascular events and individual cardiovascular events in patients with rheumatoid arthritis treated with (A) tumour necrosis factor inhibitors; (B) methotrexate; (C) non-steroidal anti-inflammatory drugs; or (D) corticosteroids in controlled studies. Size of data markers indicates relative weight of the study (from random-effects analysis). COX-2, cyclooxygenase-2; CVE, cardiovascular event; MACE, major adverse cardiac event; MTX, methotrexate; RR, relative risk; TNFi, tumour necrosis factor inhibitor.
Figure 2
Figure 2
Meta-analyses of all cardiovascular events and individual cardiovascular events in patients with rheumatoid arthritis treated with (A) tumour necrosis factor inhibitors; (B) methotrexate; (C) non-steroidal anti-inflammatory drugs; or (D) corticosteroids in controlled studies. Size of data markers indicates relative weight of the study (from random-effects analysis). COX-2, cyclooxygenase-2; CVE, cardiovascular event; MACE, major adverse cardiac event; MTX, methotrexate; RR, relative risk; TNFi, tumour necrosis factor inhibitor.
Figure 2
Figure 2
Meta-analyses of all cardiovascular events and individual cardiovascular events in patients with rheumatoid arthritis treated with (A) tumour necrosis factor inhibitors; (B) methotrexate; (C) non-steroidal anti-inflammatory drugs; or (D) corticosteroids in controlled studies. Size of data markers indicates relative weight of the study (from random-effects analysis). COX-2, cyclooxygenase-2; CVE, cardiovascular event; MACE, major adverse cardiac event; MTX, methotrexate; RR, relative risk; TNFi, tumour necrosis factor inhibitor.
Figure 3
Figure 3
Funnel plots for the meta-analysis of occurrence of cardiovascular events associated with treatment with (A) tumour necrosis factor inhibitors, (B) methotrexate, (C) non-steroidal anti-inflammatory drugs and (D) corticosteroids. The importance (weight) of each study is proportional to the marker size.
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