UA-lowering with febuxostat, benzbromarone effective in hypertensive patients
Uricosuric drugs show therapeutic potential in the management of patients with hypertension and hyperuricemia, providing greater improvements in vascular function compared with uric acid (UA) synthesis inhibitors, according to a study.
A total of 20 hypertensive patients (mean age 64 years; 90 percent male) with inadequate UA control was included in the study, which consisted of three phases. Phase I involved randomization to febuxostat 40 mg (Feb) or benzbromarone 50 mg (Ben) once daily for 3 months, phase II involved administration of a combination of the previous drugs but at lower doses (Feb 20 mg/Ben 25 mg) for another 3 months, and phase III facilitated administration of either Feb or Ben once daily for 3 months in a modified crossover manner.
UA metabolism was evaluated by measuring UA excretion and clearance from blood and urine samples, whereas blood pressure (BP) measurements were taken while seated at a doctor’s office. All assessments were performed at baseline and at the end of each treatment period. Indices of organ damage were also examined.
The 9-month data showed no significant changes in BP or estimated glomerular filtration rate (eGFR) following treatment with each UA-lowering regimen. However, substantially greater changes were observed in UA with Feb/Ben than with Feb alone, as well as in UA excretion and clearance with Ben than with Feb and Feb/Ben. Other differences observed were in urinary 8-hydroxydeoxyguanosine and liver-type fatty-acid-binding protein levels which were slightly lower with Ben, and in flow-mediated dilation which was slightly higher with Feb/Ben and Ben.
Researchers noted that the low-dose combination of the UA synthesis inhibitor and uricosuric agent had greater UA-lowering effects compared with the standard dose of each agent alone. The underlying mechanism for this effect might involve xanthine oxidase (XO), an enzyme responsible for the production of UA.
“Activation of vascular XO represents an early mechanism that contributes to increased radical formation and endothelial dysfunction in the atherosclerotic disease process,” they explained.
While UA synthesis inhibitors (ie, febuxostat) inhibit the XO system and decrease oxidative stress generated during the production of UA, uricosuric agents (ie, benzbromarone) do not exert an effect on the XO pathway but has been shown to improve inflammatory markers and insulin resistance.
“Thus, combination therapy of these two drugs seems to clarify the organ-protective effects through the different mechanisms and may have been due to the different sites of action and synergistic effects,” although long-term observations about cardiovascular events may be necessary, they said.