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, Pragya Shrestha, Delamo Bekele, Kerry Wright, Rikesh Chakradhar, Maureen Dubreuil

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)993-1009
Number of pages17
JournalRheumatology and Therapy
Issue number4
StatePublished - Dec 2020


  • Ankylosing spondylitis
  • Cardiovascular
  • NSAIDs
  • Spondyloarthritis
  • TNF inhibitors

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy


Dive into the research topics of 'Effects of Therapies on Cardiovascular Events in Ankylosing Spondylitis: A Systematic Review and Meta-Analysis'. Together they form a unique fingerprint.

Cite this