NSAIDs Decrease the Odds of Adverse Cardiovascular Events in Gout

Anne Bech-Drewes

Credit: Aarhus University.

Despite previous uncertainty, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) was not linked to any increase in cardiovascular event rate in patients with gout, according to a study published in Rheumatology International.¹ In fact, treatment with NSAIDs decreased these events by 12% among this patient population.

NSAIDs have been shown to be both cardiovascular beneficial as well as cardiovascular hazardous because of the potential for hypertensive, proarrhythmic, and prothrombotic side effects. Gout flares are often treated with anti-inflammatory treatments, including NSAIDs, low-dose colchicine, and/or glucocorticoids.² Therefore, investigators determined the risk of cardiovascular adverse events associated with NSAID treatment among patients with gout.

“In patients with inflammatory conditions, such as gout, the anti-inflammatory effects of NSAIDs might balance out their cardiovascular hazard,” wrote a team of investigators led by Anne Bech-Drewes, a PhD student associated with the Department of Clinical Medicine at Aarhus University. “This risk–benefit balance is important for clinical decision-making. However, no study has examined NSAID-associated cardiovascular risks in patients with gout.”

A nationwide, population-based, case-crossover study identified all Danish patients aged ≥ 18 years diagnosed with gout between 1997 and 2020 who experienced a cardiovascular event.

Cardiovascular events included congestive heart failure, atrial fibrillation or flutter, myocardial infarction, ischemic stroke, and cardiovascular death. Exposure was the use of NSAIDs overall and were further subcategorized by type (ibuprofen, naproxen, and diclofenac), according to data from the Danish National Prescription Registry. The dates 300, 240, 180, and 120 were used prior to the outcome date as reference dates and the Mantel-Haenszel method calculated the odds ratios (ORs) with 95% confidence intervals (CIs) of the link between cardiovascular events and treatment with NSAIDs.

The cohort included 59,150 patients with a first-time gout diagnosis (12%) or those who filled a prescription for allopurinol (88%). Among the gout cohort, most (68%) were male, the median age was 72 years, 29% had no comorbidities, and 27% had a severe comorbidity burden. The most common comorbidities were hypertension (38%), additional inflammatory diseases (19%), degenerative rheumatic disease (18%), diabetes (16%), chronic pulmonary disease (15%), and chronic kidney disease (9%). Approximately half (52%) were receiving diuretics.

Overall, NSAID use decreased the odds of a cardiovascular event by 12% in patients with gout (OR = .88, 95% CI: .85 – .91). These decreased odds were reported in patients receiving both ibuprofen (OR = .92, 95% CI: .88 – .97) and naproxen (OR = .85, 95% CI: .74 – .97); however, this was not observed in the diclofenac cohort (OR = .97, 95% CI: .90 – 1.05).

Additionally, treatment with NSAIDs was linked to decreased odds of all individual components, including congestive heart failure (OR = .89, 95% CI: .83 – .94), atrial fibrillation/flutter (OR = .80, 95% CI: .75 – .85), myocardial infarction (OR = .91, 95% CI: .84 – .99), ischemic stroke (OR = .88, 95% CI: .81 – .95), and cardiovascular death (OR = .60, 95% CI: .56 – .65) when compared with not using NSAIDs. Any NSAID treatment was linked to a decreased risk of cardiovascular events in patients without a previous cancer diagnosis (OR = .87, 95% CI: .84 – .90).

After stratifying by sex, the data remained robust; however, the interpretation of the age- and comorbidity-stratified results was hindered by low precision.

Investigators noted the large cohort of patients strengthened the study. Additionally, selection bias was reduced as these patients had free access to health care and the long-term follow-up period was virtually complete. However, there is a risk of misclassifying in-hospital NSAID users or over-the-counter ibuprofen users as non-users.

“This information may be taken into consideration when selecting NSAIDs for patients with gout,” investigators concluded.

References

1. ^{Bech-Drewes A, Bonnesen K, Hauge EM, Schmidt M. Cardiovascular safety of using non-steroidal anti-inflammatory drugs for gout: a Danish nationwide case-crossover study. Rheumatol Int. Published online April 6, 2024. doi:10.1007/s00296-024-05584-7}
2. ^{Mikuls TR (2022) Gout. N Engl J Med 387(20):1877–1887. https://doi.org/10.1056/NEJMcp2203385}