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Cardiovascular safety of using non-steroidal anti-inflammatory drugs for gout: a Danish nationwide case-crossover
Anne Bech-Drewes1,2, Kasper Bonnesen3,4, Ellen-Magrethe Hauge4,5
1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. anne.drewes@clin.au.dk.
Insights
Non-steroidal anti-inflammatory drugs (NSAIDs) use in gout patients was associated with a reduced risk of cardiovascular events. Ibuprofen and naproxen showed a better cardiovascular safety profile compared to diclofenac.
Area of Science:
- Cardiovascular medicine
- Rheumatology
- Pharmacology
Background:
- Gout attacks necessitate treatment with uric-lowering and anti-inflammatory drugs.
- Non-steroidal anti-inflammatory drugs (NSAIDs) present a dual risk/benefit profile in gout patients, potentially offering cardiovascular benefits via anti-inflammatory actions while posing risks due to prothrombotic, hypertensive, and proarrhythmic effects.
Purpose of the Study:
- To investigate the association between non-steroidal anti-inflammatory drug (NSAID) use and the risk of cardiovascular events in patients diagnosed with gout.
Main Methods:
- A nationwide, population-based case-crossover study was conducted involving Danish individuals aged 18 years and older with a first-time gout diagnosis between 1997 and 2020.
- The study analyzed 59,150 patients who experienced a cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death).
- Exposure to NSAIDs (overall and specific types: ibuprofen, naproxen, diclofenac) was assessed using reference periods prior to the event date, with analysis employing the Mantel-Haenszel method.
Main Results:
- Overall NSAID use was linked to a 12% decreased odds of a cardiovascular event (OR=0.88, 95% CI: 0.85-0.91).
- This reduced risk was observed for ibuprofen (OR=0.92, 95% CI: 0.88-0.97) and naproxen (OR=0.85, 95% CI: 0.74-0.97), but not for diclofenac (OR=0.97, 95% CI: 0.90-1.05).
- NSAID use demonstrated decreased odds for all individual components of the composite cardiovascular outcome, with no increased cardiovascular event rate observed.
Conclusions:
- Non-steroidal anti-inflammatory drug (NSAID) use is not associated with an increased cardiovascular event rate in patients with gout.
- Ibuprofen and naproxen appear to possess more favorable cardiovascular risk profiles compared to diclofenac in this patient population.
Abstract:
Gout attacks are treated with uric-lowering and anti-inflammatory drugs. In patients with gout, non-steroidal anti-inflammatory drugs (NSAIDs) could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic side effects. We, therefore, examined the risk of cardiovascular events associated with NSAID use in patients with gout. 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 cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death) (n = 59,150). The exposure was use of NSAIDs, overall and according to type (ibuprofen, naproxen, or diclofenac). We used the dates 300, 240, 180, and 120 before the outcome date as reference dates. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and cardiovascular events. NSAID use was overall associated with 12% decreased odds of a cardiovascular event (OR = 0.88, 95% CI: 0.85-0.91). This decreased odds ratio was observed for the use of ibuprofen (OR = 0.92, 95% CI: 0.88-0.97) and naproxen (OR = 0.85, 95% CI: 0.74-0.97), but not for the use of diclofenac (OR = 0.97, 95% CI: 0.90-1.05). Overall, use of NSAIDs was associated with decreased odds of all the individual components of the composite outcome. NSAIDs were not associated with an increased cardiovascular event rate when used in gout patients. Ibuprofen and naproxen appeared to have better cardiovascular risk profiles than diclofenac.
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