Probenecid may have cardioprotective effects in patients with gout
medwireNews: Results of a large observational study suggest that older patients with gout who are treated with probenecid may have a lower risk for cardiovascular events than those taking allopurinol.
As reported in the Journal of the American College of Cardiology, the researchers used the Medicare database to compare cardiovascular risk in 9722 probenecid-treated patients and 29,166 propensity score-matched allopurinol users.
Patients were aged a mean of 76 years, and had high rates of comorbidities, including hypertension (91%), hyperlipidemia (76%), diabetes (46%), and chronic kidney disease (CKD; 28%).
In all, 2.09% of patients in the probenecid group experienced the composite endpoint of hospitalization for myocardial infarction or stroke over a median follow-up of 118 days, compared with 4.05% of allopurinol-treated patients, who had a median follow-up of 358 days.
These results translated into corresponding incidence rates of 2.36 versus 2.83 per 100 person–years, giving a significant hazard ratio (HR) of 0.80 in favor of probenecid, report Seoyoung Kim, from Brigham and Women’s Hospital in Boston, Massachusetts, USA, and study co-authors.
Probenecid was also associated with a significantly lower risk for myocardial infarction (HR=0.81), stroke (HR=0.72), and all-cause mortality (HR=0.87) compared with allopurinol, and the results remained consistent in subgroup analyses of patients with and without cardiovascular disease and CKD at baseline.
“Given the high [cardiovascular] morbidity and mortality in gout patients, [the] potential positive effects of probenecid should be further examined,” say Kim and colleagues.
Writing in an accompanying editorial comment, Michael Givertz, also from Brigham and Women’s Hospital, cautions that although “it might be tempting” to alter clinical practice in light of these findings, for example by prescribing probenecid rather than allopurinol for older patients with gout, “there remain practical hurdles of uricosuric therapy” such as renal contraindications and gastrointestinal side effects.
“More importantly, these observational data are hypothesis-generating only,” he stresses.
The study authors agree, noting that their study was limited by potentially confounding factors and a “large difference” in treatment adherence between the two groups, with probenecid-treated patients adhering to treatment on only 39.8% of 180 days, compared with 87.3% of 180 days for the allopurinol group.
And Givertz concludes that “only a long-term, clinical event-driven trial will provide the safety and efficacy data needed to change clinical practice.”
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