Effects of Therapies on Cardiovascular Events in Ankylosing Spondylitis: A Systematic Review and Meta-Analysis
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ORIGINAL RESEARCH
Effects of Therapies on Cardiovascular Events in Ankylosing Spondylitis: A Systematic Review and Meta-Analysis Paras Karmacharya
. Ravi Shahukhal . Cynthia S. Crowson .
M. Hassan Murad . John M. Davis III . Pragya Shrestha . Delamo Bekele . Kerry Wright . Rikesh Chakradhar . Maureen Dubreuil
Received: September 16, 2020 / Accepted: October 19, 2020 Ó The Author(s) 2020
ABSTRACT 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 Electronic Supplementary Material The online version of this article (https://doi.org/10.1007/s40744020-00248-x) contains supplementary material, which is available to authorized users. P. Karmacharya (&) C. S. Crowson J. M. Davis III D. Bekele K. Wright R. Chakradhar Division of Rheumatology, Mayo Clinic, Rochester, MN, USA e-mail: [email protected] R. Shahukhal Lakes Regional General Hospital, Laconia, NH, USA C. S. Crowson Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA M. H. Murad Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA P. Shrestha Precision Population Science Lab, Mayo Clinic, Rochester, MN, USA M. Dubreuil Boston University School of Medicine, Boston, MA, USA
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. Metaanalysis 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
Rheumatol Ther
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 ro
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