The researchers randomized a total of 6,190 patients in North America to receive either febuxostat or allopurinol. They followed the patients for a median of 32 months and a maximum of 85 months. The median duration of exposure to febuxostat was 728 days, and the median duration of exposure to allopurinol was 719 days. In the febuxostat group, 61% of patients received 40 mg febuxostat and 39% received 80 mg febuxostat daily as the final adjusted dose. In the allopurinol group, 21.8% of patients received 200 mg allopurinol, 44.6% received 300 mg allopurinol, 25.2% received 400 mg allopurinol, 4.3% received 500 mg allopurinol and 4.1% received 600 mg allopurinol. The proportion of patients with a serum urate level of less than 6.0 mg/dL was higher in the febuxostat group than in the allopurinol group at Week 2 and that difference persisted in later time points, although the finding was not significant.
The investigators note that many participants—approximately half from each study arm—discontinued their treatment and/or did not complete follow up. Specifically, 56.6% of patients discontinued the trial regimen and 45.0% discontinued follow up. The baseline characteristics of those patients who completed the trial visits and those who did not complete the trial visits were balanced.
The modified intention-to-treat analysis revealed that the primary endpoint (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or unstable angina with urgent revascularization) occurred in 10.8% of febuxostat-treated patients and 10.4% of allopurinol-treated patients. These primary endpoint events occurred at a median period of 32 months. When the researchers performed a pre-specified analysis of events that occurred during receipt of the trial drug or within 30 days after discontinuation of treatment, they found that all-cause and cardiovascular mortality was higher in the febuxostat group than the allopurinol group, with a hazard ratio of 1.22 for cardiovascular death [95% confidence interval (CI), 1.01 to 1.47] and hazard ratio of 1.34 for cardiovascular death [95% CI, 1.03 to 1.73]. The results were similar when the investigators analyzed events that occurred while patients were being treated—as opposed to modified by the intention-to-treat analysis. | ← Previous | | | Next → | Single Page