Postdoc Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Denmark
Background: Gout is associated with increased cardiovascular risk through inflammation and shared risk factors. Gout attacks are treated with a uric-lowering drug, such as allopurinol, and an anti-inflammatory drug, such as a non-steroidal anti-inflammatory drug (NSAID). NSAIDs could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic actions. However, no study has examined the cardiovascular safety of NSAIDs for the treatment of gout.
Objectives: To examine the risk of major adverse cardiovascular events (MACEs) associated with NSAID use in patients with gout.
Methods: We conducted a nationwide, population-based case-crossover study of all Danes ≥18 years of age with first-time gout during 1997–2020, who experienced a MACE (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, or all-cause death) (n=103,522). The patients were identified either via a hospital diagnosis for gout (12%) or via a filling of an allopurinol prescription (88%). The exposures were use of NSAIDs overall and according to subtype (ibuprofen, naproxen, or diclofenac). An individual was considered exposed from the time of a filled prescription until the end of an exposure period, estimated from average use of two tablets per day. In the case-crossover design, we compared use of ibuprofen at one of four reference dates at 120, 180, 240, or 300 days before the outcome with use of ibuprofen at the outcome date. An individual was considered exposed if the exposure period covered a reference date or the outcome date. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and MACE.
Results: NSAID use was overall associated with a 15% decreased risk of MACE (OR=0.85, 95% CI: 0.83–0.87). The ORs of the association between NSAID use and the individual cardiovascular events were 0.91 (95% CI: 0.84–0.99) for myocardial infarction, 0.88 (95% CI: 0.81–0.95) for ischemic stroke, 0.89 (95% CI: 0.83–0.94) for congestive heart failure, 0.80 (95% CI: 0.75–0.85) for atrial fibrillation or flutter, and 0.77 (95% CI: 0.75–0.80) for all-cause death. The decreased risk of MACE was observed for use of ibuprofen (OR=0.91, 95% CI: 0.88–0.95) and naproxen (OR=0.78, CI: 0.70–0.86), but not for use of diclofenac (OR=1.03, 95% CI: 0.97–1.09).
Conclusions: In patients with first-time gout, use of ibuprofen and naproxen was associated with a slightly decreased cardiovascular risk, whereas diclofenac was not.
