TY - JOUR
T1 - Effects of Therapies on Cardiovascular Events in Ankylosing Spondylitis
T2 - A Systematic Review and Meta-Analysis
AU - Karmacharya, Paras
AU - Shahukhal, Ravi
AU - Crowson, Cynthia S.
AU - Murad, M. Hassan
AU - Davis, John M.
AU - Shrestha, Pragya
AU - Bekele, Delamo
AU - Wright, Kerry
AU - Chakradhar, Rikesh
AU - Dubreuil, Maureen
N1 - Funding Information:
We would like to thank our librarian, Larry Prokop, for help with the extensive search strategy, and Dr. Premarani Sinnathurai (Lee et al. study) [23 ] and Dr. Lars Erik Kristensen [32 ] for providing additional data. This project was supported by CTSA Grant Number UL1 TR002377 from the National Center for Advancing Translational Science (NCATS) (PK), T32 AR56950 grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases for the Musculoskeletal Research Training Program (PK), NIH AR0691427 (MD), AR04775 (MD), and T32 GM08685 (PS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. No direct financial support was received for this project. No Rapid Service Fee was received by the journal for the publication of this article. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. PK conceived, designed, and wrote the initial draft of the study; PK, RS, PS participated in the abstraction, analysis, and interpretation of data. DB, CSC, MHM, JMD, KW, RK, and MD analyzed, interpreted, and provided intellectual content, edited subsequent draft, and approved the final article. P.K. is responsible as overall guarantor of the content. This manuscript is based on work that has been previously presented at the Spondyloarthritis Research and Treatment Network (SPARTAN) Annual Meeting in Madison, WI, May 2019, and American College of Rheumatology (ACR) Annual Meeting, Atlanta, November 2019. John M. Davis III has received consulting fees and/or honoraria from AbbVie and Sanofi-Genzyme (less than $10,000 each) and research support from Pfizer, and is a member of the journal's Editorial Board. Maureen Dubreuil has received consulting fees and/or honoraria from UCB (less than $10,000). Paras Karmacharya, Ravi Shahukhal, Cynthia S. Crowson, M. Hassan Murad, Pragya Shrestha, Delamo Bekele, Kerry Wright, and Rikesh Chakradhar have nothing to disclose. This article is based on secondary analysis of previously conducted and published studies and does not contain any data with human participants or animals performed by any of the authors. All data generated or analyzed are available in this article or the supplementary file.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor inhibitors (TNFi) are the most common therapies used in AS, however, the associated long-term cardiovascular risk is unclear. We performed a systematic review and meta-analysis on the association of therapies used for ankylosing spondylitis (AS) such as NSAIDs and TNFi on cardiovascular events (CVE) in AS. Methods: A comprehensive search was performed from database inception to May 29, 2020 to include controlled studies of AS treated with NSAIDs, oral small molecules, or biologics reporting CVE. Study-specific risk ratios (RR) were pooled using a random effects model. Results: Nine non-randomized studies from 1570 studies screened fulfilled inclusion criteria. Among NSAID users as a whole versus no NSAIDs, no increased risk of CVE (composite outcome) was observed; however, the risk of cerebrovascular accident was significantly lower (RR 0.58, 95% CI 0.37–0.93, I2 = 66%). Cox-2 inhibitor use was associated with reduced risk of all CVE (RR 0.48, 95% CI 0.33–0.70, I2 = 0%). Non-selective NSAIDs were not associated with any increased/decreased risk of any CVE. Meta-analysis of three studies of MI did not show a significant association with TNFi (RR 0.88, 95% CI 0.57–1.35, I2 = 76%). Conclusions: In this meta-analysis of non-randomized studies, NSAID users as a whole and users of non-selective NSAIDs did not seem to have a higher risk of any CVE. Limited data suggest a lower risk of composite CVE outcome with Cox-2 inhibitors, unlike the increased risk reported in the general population. No significant association between TNFi and MI was observed. The certainty in evidence was very low due to all studies being observational. More studies are needed to study the association between TNFi use and CVE in general to evaluate a possible protective role in AS.
AB - Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor inhibitors (TNFi) are the most common therapies used in AS, however, the associated long-term cardiovascular risk is unclear. We performed a systematic review and meta-analysis on the association of therapies used for ankylosing spondylitis (AS) such as NSAIDs and TNFi on cardiovascular events (CVE) in AS. Methods: A comprehensive search was performed from database inception to May 29, 2020 to include controlled studies of AS treated with NSAIDs, oral small molecules, or biologics reporting CVE. Study-specific risk ratios (RR) were pooled using a random effects model. Results: Nine non-randomized studies from 1570 studies screened fulfilled inclusion criteria. Among NSAID users as a whole versus no NSAIDs, no increased risk of CVE (composite outcome) was observed; however, the risk of cerebrovascular accident was significantly lower (RR 0.58, 95% CI 0.37–0.93, I2 = 66%). Cox-2 inhibitor use was associated with reduced risk of all CVE (RR 0.48, 95% CI 0.33–0.70, I2 = 0%). Non-selective NSAIDs were not associated with any increased/decreased risk of any CVE. Meta-analysis of three studies of MI did not show a significant association with TNFi (RR 0.88, 95% CI 0.57–1.35, I2 = 76%). Conclusions: In this meta-analysis of non-randomized studies, NSAID users as a whole and users of non-selective NSAIDs did not seem to have a higher risk of any CVE. Limited data suggest a lower risk of composite CVE outcome with Cox-2 inhibitors, unlike the increased risk reported in the general population. No significant association between TNFi and MI was observed. The certainty in evidence was very low due to all studies being observational. More studies are needed to study the association between TNFi use and CVE in general to evaluate a possible protective role in AS.
KW - Ankylosing spondylitis
KW - Cardiovascular
KW - NSAIDs
KW - Spondyloarthritis
KW - TNF inhibitors
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U2 - 10.1007/s40744-020-00248-x
DO - 10.1007/s40744-020-00248-x
M3 - Article
AN - SCOPUS:85111406000
VL - 7
SP - 993
EP - 1009
JO - Rheumatology and Therapy
JF - Rheumatology and Therapy
SN - 2198-6576
IS - 4
ER -