Background: Febuxostat is a nonpurine inhibitor which inhibits xanthine oxidase to decrease the synthesis of uric acid thereby treating gout. According to the UpToDateTM reports, the febuxostat dose should be adjusted if creatinine clearance is less than 30 ml/min. In 2017, the US Food and Drug Administration (FDA) announced drug safety communications about the increased risk of all-cause mortality rate and cardiovascular death with febuxostat compared to allopurinol and added a black-box warning on the label of febuxostat. FDA has also limited the approved use of febuxostat to patients who are not treated effectively or experience severe adverse effects of allopurinol.
Objectives: We assessed patients in our center to evaluate the risk of related events.
Methods: We evaluated patients who used febuxostat and allopurinol in our center in 2017 and excluded patients who had cardiovascular disease history or had visited cardiology clinic before. We reviewed the patients who visited the cardiology clinic or took clopidogrel in 2018 and investigated the risk factors announced in FDA drug safety communication, including (1) cardiovascular death (2) nonfatal myocardial infarction (3) nonfatal stroke (4) unstable angina with urgent coronary revascularization. Furthermore, the patients’ febuxostat dose was evaluated according to the suggested dose.
Results: The numbers of patients who meet the criteria above were 617 in the febuxostat group and 469 in the allopurinol group. Overall there were 6 adverse events in the febuxostat group and 4 adverse events in the allopurinol group, hazard ratio of 1.247 (95% CI 0.35-4.44). In the group of febuxostat, there were 4 patients who occurred nonfatal stroke (0.65%), and 2 of them did not adjust the dose based on their renal function. Two patients occurred unstable angina with urgent coronary revascularization (0.32%), and 1 of them did not adjust the dose based on renal function. In the group of allopurinol, there was 1 patient who occurred nonfatal stroke (0.21%) and 3 patients who occurred unstable angina with urgent coronary revascularization (0.64%).
Conclusions: According to the assessment of cardiovascular risk between febuxostat and allopurinol, there was no statistical difference between both groups. But for the patients who occurred cardiovascular events in the febuxostat group, two of them did not meet the requirement of renal dose. We suggest that overdose could be related to the incidence of a cardiovascular events. Clinical professionals should be careful of the dosage adjustment for patients with renal dysfunction.
