Cohort study examining the association of immunosuppressant drug prescription with major adverse cardiovascular and limb events in patients with peripheral artery disease

Golledge, Jonathan, Velu, Ramesh, Quigley, Frank, Jenkins, Jason, and Singh, Tejas P. (2021) Cohort study examining the association of immunosuppressant drug prescription with major adverse cardiovascular and limb events in patients with peripheral artery disease. Annals of Vascular Surgery, 78. pp. 310-320.

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Abstract

Aim: Immune activation is strongly implicated in atherosclerotic plaque instability, however, the effect of immunosuppressant drugs on cardiovascular events in patients with peripheral artery disease (PAD) is not known. The aim of this study was to assess whether prescription of one or more immune suppressant drugs was associated with a lower risk of major adverse cardiovascular (MACE; i.e. myocardial infarction, stroke or cardiovascular events) or limb events (MALE; i.e. major amputation or requirement for peripheral revascularization) in patients with PAD.

Methods: A total of 1506 participants with intermittent claudication ( n = 872) or chronic limb threatening ischemia (CLTI; n = 634) of whom 53 (3.5%) were prescribed one or more immunosuppressant drugs (prednisolone 41; methotrexate 17; leflunomide 5; hydroxychloroquine 3; azathioprine 2; tocilizumab 2; mycophenolate 1; sulfasalazine 1; adalimumab 1) were recruited from 3 Australian hospitals. Participants were followed for a median of 3.9 (inter-quartile range 1.2, 7.3) years. The association of immunosuppressant drug prescription with MACE or MALE was examined using Cox proportional hazard analyses.

Results: After adjusting for other risk factors, prescription of an immunosuppressant drug was associated with a significantly greater risk of MACE (Hazard ratio, HR, 1.83, 95% confidence intervals, CI, 1.11, 3.01; P = 0.017) but not MALE (HR 1.32, 95% CI 0.90, 1.92; P = 0.153). In a sub-analysis restricted to participants with CLTI findings were similar: MACE (HR 2.44, 95% CI 1.32, 4.51; P = 0.005); MALE (HR 1.38, 95% CI 0.87, 2.19; P = 0.175); major amputation (HR 1.37, 95% CI 0.49, 3.86; P = 0.547).

Conclusions: This cohort study suggested that immunosuppressant drug therapy is associated with a greater risk of MACE amongst patients with PAD.

Item ID: 70568
Item Type: Article (Research - C1)
ISSN: 1615-5947
Keywords: immunosuppression, major adverse cardiovascular events, major adverse limb events, major amputation, Peripheral artery disease
Copyright Information: Copyright © 2022. Elsevier Inc. All rights reserved.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC 1063476, NHMRC 1180736
Date Deposited: 05 Apr 2022 01:51
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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