Factors associated with risk of major adverse cardiovascular events in patients with rheumatoid arthritis: a nationwide, population-based, case-control study

Abstract

Objectives: To investigate factors associated with major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA). Methods: We conducted a nationwide, population-based, case-control study using Taiwan’s National Health Insurance Research Database for 2003–2013. From 2004 to 2012, we identified 108,319 newly diagnosed RA patients without previous MACEs, of whom 7,580 patients (7.0%) developed MACEs during follow-up. From these incident RA patients, we included 5,994 MACE cases and 1:4 matched 23,976 non-MACE controls for analysis. The associations of MACEs with comorbidities and use of anti-rheumatic medications within 1 year before the index date were examined using conditional logistic regression analyses. Results: Using multivariable conditional logistic regression analysis, the risk of MACE in RA patients was associated with use of golimumab [odd’s ratio (OR), 0.09; 95% confidence interval (CI), 0.01-0.67], abatacept (OR, 0.13; 95% CI, 0.02–0.93), hydroxychloroquine (OR, 0.90; 95% CI, 0.82-0.99), methotrexate (OR, 0.72; 95% CI, 0.64–0.81), cyclosporin (OR, 1.43; 95% CI, 1.07–1.91), nonsteroidal anti-inflammation drugs (NSAIDs) (OR, 1.36; 95% CI, 1.27–1.46), antiplatelet agent (OR, 2.47; 95% CI, 2.31-2.63), hypertension (without anti-hypertensive agents: OR, 1.04; 95% CI, 0.96-1.12; with anti-hypertensive agents: OR, 1.47; 95% CI, 1.36-1.59), diabetes (OR, 1.27; 95% CI, 1.18-1.37), hyperlipidemia without lipid-lowering agents (OR, 1.09; 95% CI, 1.01-1.17), ischemic heart disease (OR, 1.20; 95% CI, 1.10-1.31), and chronic obstructive pulmonary disease (COPD) (OR, 1.12; 95% CI, 1.03-1.23) in the parsimonious model. The risk of MACE in RA patients also increased markedly in participants younger than 65 years with some comorbidities. Conclusions: This population-based case-control study revealed that the use of golimumab, abatacept, hydroxychloroquine, and methotrexate were associated with a decreased risk of MACE development in newly diagnosed RA patients, while the use of cyclosporin, NSAIDs, and antiplatelet agents, and comorbidities, including hypertension, diabetes, hyperlipidemia without lipid-lowering agent therapy, ischemic heart disease, and COPD, were associated with an increased risk of MACE development in RA patients.

Safety of biological therapy in patients with rheumatoid arthritis in administrative health databases: A systematic review and meta-analysis

“…Thirty-one studies were eligible for inclusion in the present systematic review; eleven population-based cohorts ( Arkema et al, 2015 ; Raaschou et al, 2015 ; Mercer et al, 2015; Mercer et al, 2017 ; Desai et al, 2016 ; Low et al, 2017 ; Dreyer et al, 2018 ; Chen et al, 2020 ; Kim et al, 2020 ; Pettipher and Benitha, 2020 ; Hellgren et al, 2021 ), eight prospective ( Listing et al, 2015 ; Richter et al, 2016 ; Meissner et al, 2017 ; Rutherford et al, 2018 ; Grøn et al, 2019; Grøn et al, 2020 ; Rahman et al, 2020 ; Ozen et al, 2021 ) and eight retrospective cohorts ( Yun et al, 2014 ; 2016 ; Curtis et al, 2016 ; Zhang et al, 2016 ; Kim et al, 2017 ; Pawar et al, 2019 ; 2020 ; Patel et al, 2021 ), and four case-control studies ( Harada et al, 2017 ; Sakai et al, 2018 ; de Germay et al, 2020 ; Chen et al, 2021 ), published from 2014 to 2021 ( Supplementary Table S3 ).…”

“…The mean age ranged between 46 and 78 years and most were women (60–100%). Mean disease duration was reported by thirteen studies and ranged between 3.4 and 16.5 years ( Listing et al, 2015 ; Raaschou et al, 2015 ; Richter et al, 2016 ; Harada et al, 2017 ; Low et al, 2017 ; Meissner et al, 2017 ; Dreyer et al, 2018 ; Rutherford et al, 2018 ; Grøn et al, 2019 ; Rahman et al, 2020 ; Chen et al, 2021 ; Hellgren et al, 2021 ; Ozen et al, 2021 ). Among the thirteen studies which described mean disease activity, RA patients had moderate to high disease activity ( Listing et al, 2015 ; Raaschou et al, 2015 ; Richter et al, 2016 ; Harada et al, 2017 ; Low et al, 2017 ; Meissner et al, 2017 ; Dreyer et al, 2018 ; Rutherford et al, 2018 ; Grøn et al, 2019 ; Kim et al, 2020 ; Pettipher and Benitha, 2020 ; Rahman et al, 2020 ; Hellgren et al, 2021 ) ( Table 1 ).…”

“…According to the NOS, 27 studies were classified as high quality, of which seven were “nine stars” ( Mercer et al, 2015 , 2017 ; Zhang et al, 2016 ; Meissner et al, 2017 ; Pawar et al, 2019 ; Chen et al, 2020 ; Hellgren et al, 2021 ), fifteen were “eight stars” ( Yun et al, 2014 , 2016 ; Arkema et al, 2015 ; Listing et al, 2015 ; Richter et al, 2016 ; Desai et al, 2016 ; Kim et al, 2017 ; Low et al, 2017 ; Rutherford et al, 2018 ; Dreyer et al, 2018 ; Grøn et al, 2019; Grøn et al, 2020 ; Pawar et al, 2020 ; Chen et al, 2021 ; Ozen et al, 2021 ), and five were “seven stars” ( Raaschou et al, 2015 ; Curtis et al, 2016 ; de Germay et al, 2020 ; Kim et al, 2020 ; Patel et al, 2021 ). Four studies were considered moderate quality, of which two scored “six stars” ( Harada et al, 2017 ; Sakai et al, 2018 ), one “five stars” ( Rahman et al, 2020 ), and one “four stars” ( Pettipher and Benitha, 2020 ) ( Supplementary Table S4 ).…”

“…The safety of TNFi versus non-TNFi was assessed by 19 studies ( Yun et al, 2014 , 2016 ; Listing et al, 2015 ; Curtis et al, 2016 ; Richter et al, 2016 ; Zhang et al, 2016 ; Harada et al, 2017 ; Kim et al, 2017 , 2020 ; Meissner et al, 2017 ; Rutherford et al, 2018 ; Sakai et al, 2018 ; Pawar et al, 2019 , 2020 ; Chen et al, 2020 , 2021 ; Pettipher and Benitha, 2020 ; Ozen et al, 2021 ; Patel et al, 2021 ). The meta-analysis revealed no significant differences in the safety of TNFi compared to non-TNFi (RR 1.08; 95% CI 0.92–1.28; p < 0.01; I 2 = 93.0%).…”

Cardiovascular Disease Risk in Rheumatoid Arthritis Anno 2022

“…Hypertension has also been described as a possible side effect of 1–10% [ 67 ]. However, the CVD reduction due to the anti-inflammatory effect of abatacept seems to not be affected [ 68 , 69 ].…”