NSAIDs May Pose Greater Heart Risks Than Colchicine in Gout
In patients with gout starting allopurinol as a long-term urate-lowering therapy, the prophylactic use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a higher risk for major adverse cardiovascular events (MACEs) than the use of colchicine or no prophylaxis.
METHODOLOGY:
Researchers followed a target trial framework to emulate a randomized clinical trial using data from administrative databases in British Columbia, Canada, to compare the cardiovascular safety of the prophylactic use of NSAIDs vs colchicine in patients with gout who started allopurinol between 1995 and 2022.
They included 9060 patients who were prescribed NSAIDs (mean age, 60.9 years; 83.5% men) who were propensity score-matched with 9060 patients prescribed colchicine on the same day as allopurinol.
The primary outcome was MACE, a composite of myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes included the individual components of MACE and all-cause mortality.
Sensitivity analyses were also conducted with follow-up truncated after 3 months or 6 months and using inverse probability treatment weighting.
Additionally, the cardiovascular safety of NSAIDs and colchicine was compared with that of no prophylaxis after propensity matching.
TAKEAWAY:
The risk for MACE was higher in patients using NSAIDs than in those using colchicine (hazard ratio [HR], 1.56; 95% CI, 1.11-2.17). Findings were consistent in sensitivity analyses.
The use of NSAIDs was associated with significantly higher risks for cardiovascular death (HR, 2.50; 95% CI, 1.14-5.26) and all-cause mortality (HR, 2.00; 95% CI, 1.19-3.45) than the use of colchicine.
Compared with no prophylaxis, the use of NSAIDs was associated with a 50% higher risk for MACE (HR, 1.50; 95% CI, 1.17-1.91) and a 93% higher risk for myocardial infarction (HR, 1.93; 95% CI, 1.35-2.75), whereas the use of colchicine was not associated with risk for MACE or its individual components.
IN PRACTICE:
'The findings of this present study have the potential to impact clinical care as well as current guidelines, as they highlight the real potential dangers of NSAID use, even short-term, among patients with gout and provide additional evidence in support of colchicine as the preferred paradoxical gout flare prophylaxis agent,' the authors wrote.
SOURCE:
This study was led by Chio Yokose, MD, MSc, Massachusetts General Hospital, Boston. It was published online on May 26, 2025, in Arthritis & Rheumatology .
LIMITATIONS:
The risk for residual confounding factors remained owing to the observational nature of this study. Data on key cardiovascular risk factors such as use of tobacco, BMI, or lipid panel were unavailable. Cardiovascular risk associated with different types of NSAID was not analyzed.
DISCLOSURES:
Some authors reported receiving support from the National Institutes of Health and the Canadian Institutes of Health Research. Several authors reported receiving personal fees, consulting fees, royalties, and grants, and having board positions and other financial ties with multiple pharmaceutical and healthcare companies.
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