Higher NSAID Dose Raises CVD Risk in Ankylosing Spondylitis


Higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk for cardiovascular diseases (CVDs) such as ischemic heart disease, stroke, and congestive heart failure in patients with ankylosing spondylitis (AS) compared with lower doses.


  • NSAIDs can suppress inflammation and relieve pain in patients with AS, but long-term treatment with NSAIDs poses concerns regarding gastrointestinal and renal toxicities and increased CVD risk.
  • This nationwide cohort study used data from the Korean National Health Insurance database to investigate the risk for CVD associated with an increasing NSAID dosage in a real-world AS cohort.
  • Investigators recruited 19,775 patients (mean age, 36.1 years; 75% men) with newly diagnosed AS and without any prior CVD between January 2010 and December 2018, among whom 99.7% received NSAID treatment and 30.2% received tumor necrosis factor inhibitor treatment.
  • A time-varying approach was used to assess the NSAID exposure, wherein periods of NSAID use were defined as “NSAID-exposed” and periods longer than 1 month without NSAID use were defined as “NSAID-unexposed.”
  • The primary outcome was the composite outcome of ischemic heart disease, stroke, or congestive heart failure.


  • During the follow-up period of 98,290 person-years, 1663 cases of CVD were identified, which included 1157 cases of ischemic heart disease, 301 cases of stroke, and 613 cases of congestive heart failure.
  • After adjusting for confounders, each defined daily dose increase in NSAIDs raised the risk for incident CVD by 10% (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.08-1.13).
  • Similarly, increasing the dose of NSAIDs was associated with an increased risk for ischemic heart disease (aHR, 1.08; 95% CI, 1.05-1.11), stroke (aHR, 1.09; 95% CI, 1.04-1.15), and congestive heart failure (aHR, 1.12; 95% CI, 1.08-1.16).
  • The association between increasing NSAID dose and increased CVD risk was consistent across various subgroups, with NSAIDs posing a greater threat to cardiovascular health in women than in men.


The authors wrote, “Taken together, these results suggest that increasing the dose of NSAIDs is associated with a higher cardiovascular risk in AS, but that the increased risk might be lower than that in the general population.”


First author Ji-Won Kim, MD, PhD, of the Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, the Republic of Korea, and colleagues had their work published online on April 9 in Annals of the Rheumatic Diseases.


The study was of retrospective nature. The levels of acute phase reactants and AS disease activity could not be determined owing to a lack of data in the National Health Insurance database. The accuracy of the diagnosis of cardiovascular outcomes on the basis of the International Classification of Disease codes was also questionable.


The study was supported by the National Research Foundation of Korea. The authors declared no conflicts of interest.

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