Effects of intensive urate lowering therapy with febuxostat in comparison with allopurinol on pulse wave velocity in patients with gout and increased cardiovascular risk: the FORWARD study.

Abstract

Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels. A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia. In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.