Probenecid linked to decreased CVD risk in patients with gout
Patients with gout who were treated with probenecid had a modestly decreased risk for cardiovascular events including myocardial infarction, stroke and heart failure exacerbation, compared with those treated with allopurinol, according to findings published in the Journal of the American College of Cardiology.
“Inflammation plays a critical role in the pathogenesis of both gout and CVD,” Seoyoung C. Kim, MD, ScD, MSCE, from Brigham and Women’s Hospital and Harvard Medical School, told Healio Rheumatology. “In particular, IL-1b is the main cytokine involved in gout pathogenesis. Probenecid lowers serum uric acid by blocking reuptake of uric acid in the kidneys and may exhibit an anti-inflammatory effect through its inhibition of pannexin 1 channels, thereby reducing IL-1b. Therefore, it is plausible to hypothesize that probenecid may have cardioprotective effects in gout patients.”
According to Kim, although both probenecid and allopurinol have been available for a long time for patients with gout, this study is the first to evaluate the cardiovascular effect of probenecid directly vs. allopurinol in a population-representative cohort.
To determine the relative cardiovascular safety of probenecid and allopurinol, the researchers evaluated claims data from Medicare Parts A, B and D, spanning from 2008 through 2013, focusing on patients with gout who received one of the two drugs. The researchers identified 9,722 patients who initiated probenecid and matched them to 29,166 patients who had received allopurinol.
The study’s primary outcome was hospitalization for myocardial infarction or stroke, with coronary revascularization, heart failure and mortality identified as secondary outcomes. The researchers estimated incidence rates and hazard ratios of each primary and secondary outcome.
According to Kim and colleagues, the incidence rate of the primary composite endpoint of myocardial infarction or stroke per 100 person-years was 2.36 in the probenecid group, and 2.83 in the allopurinol cohort (HR = 0.8; 95% CI, 0.69-0.93). In addition, probenecid was associated with a decreased risk for myocardial infarction, stroke, heart failure exacerbation and mortality compared with allopurinol. The results were consistent in the subgroup analyses of patients without baseline CV disease, or those without baseline chronic kidney disease, the researchers wrote.
“In a large cohort study of 38,888 patients with gout, probenecid is associated with a modestly lower risk of cardiovascular events, including MI, stroke and heart failure exacerbation, than allopurinol, the most commonly used xanthine oxidase inhibitor for gout,” Kim said. “While our study has limitations of observational studies of drugs including confounding and suboptimal adherence to treatment, given the high cardiovascular morbidity and mortality in gout patients potential positive cardiovascular effects of probenecid should be further examined.” – by Jason Laday
Disclosure: Kim reports funding support from the NIH and research grants to Brigham and Women’s Hospital from AstraZeneca, Bristol-Myers Squibb, Merck, Pﬁzer and Roche/Genentech.