Methotrexate might reduce ischemic stroke in patients with rheumatoid arthritis: a population‐based retrospective cohort study

Tam, Hong Wei; Chen, Chyong Mei; Leong, Pui‐Ying; Chen, Chao Hsi; Li, Yuan Chao; Wang, Yu Hsun; Lin, Li Chi; Chiou, Jeng Yuan; Wei, Jing

doi:10.1111/1756-185x.13267

Cited by 18 publications

(18 citation statements)

References 26 publications

(25 reference statements)

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“…Our finding that non-AF RA patients with a CHA 2 DS 2 -VASc score of ≥2 had a higher risk of ischemic stroke is similar to the case of systemic lupus erythematosus patients without AF [25]. Previous studies have also demonstrated an increased risk of ischemic stroke 10 or more years after RA diagnosis [3,4,41]. This result was also observed in our study, especially in patients with a higher CHA 2 DS 2 -VASc score (≥2).…”

Section: Discussionsupporting

confidence: 88%

“…Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory polyarthritis with a prevalence of 0.5-1% with female predominance in industrialized countries [1]. The risk of stroke is higher in patients with RA compared with the general population or patients with noninflammatory arthropathies [2][3][4][5]. Patients with RA are also at a higher risk for long-term disability after stroke [6].…”

Section: Introductionmentioning

confidence: 99%

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Predicting the Risk of Ischemic Stroke among Patients with Rheumatoid Arthritis Using a Simplified RA-CHADSV Score Based on the CHA2DS2-VASc Score

Hsu

et al. 2020

Medicina

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Background and Objectives: The aim of this retrospective cohort study was to develop a new score (RA-CHADSV) (rheumatoid arthritis - congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, and vascular disease), modified from the CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, stroke/transient ischemic attack (doubled), vascular disease, age 65–74 years, and female), in predicting the risk of ischemic stroke in rheumatoid arthritis (RA) patients without atrial fibrillation (AF). Materials and Methods: Using the Taiwan’s National Health Insurance Research Database, 592 patients with RA diagnosed between 2000 and 2002 were identified and followed until first occurrence of ischemic stroke or the last available date in the database. Incidence rate ratios (IRR) of ischemic stroke for the CHA2DS2-VASc score were calculated using Poisson regression models. A new prediction score RA-CHADSV was developed using multiple logistic regression analysis with bootstrap validation. Results: The area under the receiver operating characteristic curve of the newly developed RA-CHADSV score and the CHA2DS2-VASc score were 0.73 (95% confidence interval (CI) 0.64–0.82) and 0.70 (95% CI 0.61–0.79), respectively. The RA-CHADSV score was significantly associated with a higher ischemic stroke incidence in the patients who scored ≥1 (adjusted IRR 7.39, p < 0.001). Conclusions: A simplified RA-CHADSV score, with comparable efficiency as the CHA2DS2-VASc score, but easier to use clinically was developed for predicting the risk of ischemic stroke among non-AF RA patients.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Predicting the Risk of Ischemic Stroke among Patients with Rheumatoid Arthritis Using a Simplified RA-CHADSV Score Based on the CHA2DS2-VASc Score

Hsu

et al. 2020

Medicina

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“…HCQ use is associated with lower low-density lipoprotein levels but not carotid artery intima media thickness in lupus nephritis patients [31]. Hydroxychloroquine has no significant protective effect on ischemic stroke in rheumatoid arthritis patients [32]. Whether HCQ therapy in SLE decreases risk of stroke is still controversial.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Hydroxychloroquine Therapy and Risk of Coronary Artery Disease in Patients with Systemic Lupus Erythematosus

Yang

Leong

Sia

et al. 2019

JCM

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Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease associated with a high prevalence of cardiovascular disease (CVD). Hydroxychloroquine (HCQ) is commonly used to control disease activity in patients with SLE. We evaluated its potential additional therapeutic effect for reducing CVD in SLE patients. We conducted a retrospective cohort study, in which one million participants were sampled from 23 million beneficiaries and data were collected from 2000 to 2013. In total, 826 SLE patients receiving HCQ medication were included after exclusion for previous CVD. The total number of SLE patients was 795 after follow-up for more than one year. After adjusting for chronic comorbidity, a significantly decreased hazard ratio (HR) for coronary artery disease (CAD) was found among SLE patients with a high usage of HCQ for at least 318 days (HR = 0.31, 95% confidence interval, CI: 0.12–0.76). A low HR for CAD was observed in SLE patients with a high cumulative dose of at least 100,267 mg HCQ (HR = 0.25, 95% CI: 0.09–0.66). However, there was no significant lowering of the HR for stroke. Long-term HCQ therapy decreases the HR of CVD in SLE patients. The cardiovascular protective effect of HCQ therapy was associated with decrease in CAD, but not stroke.

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“…102 Low-dose methotrexate was not effective in reducing stroke risk prospectively, 103 though retrospective data indicate chronic use in rheumatoid arthritis is associated with a reduced rate of ischemic stroke. 104 With IL-6 positioned as a key regulator of virus-associated cerebrovascular events, these therapies could prove beneficial in preventing virally-mediated stroke. The anti-gout medication, colchicine can also reduce IL-6 levels and may have benefit in treating cardiovascular disease including reducing ischemic stroke rates.…”

Section: Therapeutic Strategies To Target Sars-cov-2 Action In the Cerebral Vasculaturementioning

confidence: 99%

Pathophysiologic mechanisms of cerebral endotheliopathy and stroke due to Sars-CoV-2

Kakarla

Kaneko

Nour

et al. 2021

J Cereb Blood Flow Metab

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Cerebrovascular events have emerged as a central feature of the clinical syndrome associated with Sars-CoV-2 infection. This increase in infection-related strokes is marked by atypical presentations including stroke in younger patients and a high rate of hemorrhagic transformation after ischemia. A variety of pathogenic mechanisms may underlie this connection. Efforts to identify synergism in the pathophysiology underlying stroke and Sars-CoV-2 infection can inform the understanding of both conditions in novel ways. In this review, the molecular cascades connected to Sars-CoV-2 infection are placed in the context of the cerebral vasculature and in relationship to pathways known to be associated with stroke. Cytokine-mediated promotion of systemic hypercoagulability is suggested while direct Sars-CoV-2 infection of cerebral endothelial cells may also contribute. Endotheliopathy resulting from direct Sars-CoV-2 infection of the cerebral vasculature can modulate ACE2/AT1R/MasR signaling pathways, trigger direct viral activation of the complement cascade, and activate feed-forward cytokine cascades that impact the blood-brain barrier. All of these pathways are already implicated as independent mechanisms driving stroke and cerebrovascular injury irrespective of Sars-CoV-2. Recognizing the overlap of molecular pathways triggered by Sars-CoV-2 infection with those implicated in the pathogenesis of stroke provides an opportunity to identify future therapeutics targeting both Sars-CoV-2 and stroke thereby reducing the impact of the global pandemic.

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Methotrexate might reduce ischemic stroke in patients with rheumatoid arthritis: a population‐based retrospective cohort study

Abstract: At a dosage of > 0.5 defined daily dose, short-term methotrexate might decrease ischemic stroke risk in RA patients, while hydroxychloroquine and sulfasalazine were neutral.

Cited by 18 publications

References 26 publications

Predicting the Risk of Ischemic Stroke among Patients with Rheumatoid Arthritis Using a Simplified RA-CHADSV Score Based on the CHA2DS2-VASc Score

Predicting the Risk of Ischemic Stroke among Patients with Rheumatoid Arthritis Using a Simplified RA-CHADSV Score Based on the CHA2DS2-VASc Score

Long-Term Hydroxychloroquine Therapy and Risk of Coronary Artery Disease in Patients with Systemic Lupus Erythematosus

Pathophysiologic mechanisms of cerebral endotheliopathy and stroke due to Sars-CoV-2

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