Effects of Combined Antihypertensive Therapy with Losartan/Hydrochlorothiazide on Uric Acid Metabolism

Objective The Jikei Optimal Antihypertensive Treatment (JOINT) study originally evaluated the effect of a fixed-dose formulation of losartan (LOS) (50 mg) plus 12.5 hydrochrolthiazide (HCTZ) for achieving better blood pressure (BP) control in patients with uncontrolled hypertension. This study is a sub-analysis of the JOINT study, focusing on the effect of LOS/HCTZ on the uric acid (UA) metabolism. Methods Among 228 participants in the JOINT study, a total of 164 patients whose blood and urinary UA specimens were available were included in the present analyses. Results Six months after switching from the prior antihypertensive agent(s) to a single tablet formulation of LOS/HCTZ, the overall serum UA concentration (sUA) increased from 6.0 +/- 1.6 mg/dL to 6.2 +/- 1.6 mg/dL (p=0.029). The urinary UA/creatinine (Cr) ratio increased from 0.45 +/- 0.21 to 0.50 +/- 0.25 (p=0.014), and the fractional excretion of UA (FEUA) also increased, from 7.1 +/- 3.6 to 7.0 +/- 4.3, p=0.04). Multivariate regression analyses of the basal parameters showed the change in sUA (Delta UA) to correlate with the basal sUA (beta=-0.483, p < 0.001), estimated glomerular filtration rate (eGFR) (beta=-0.202, p=0.007) and systolic BP (beta=0.147, p=0.038). In addition, the Delta UA also correlated with the changes in the estimated glomerular filtration rate (Delta eGFR) (beta=-0.332, p < 0.001). When the patients were classified into two groups depending on their basal sUA, those with a basal sUA >= 7 mg/dL exhibited a decrease in their sUA, whereas the rest of those with a sUA < 7 mg/dL experienced an increase. Furthermore, patients who had previously been treated with LOS alone had a greater increase in the sUA than those treated with an angiotensin II blocker (ARB) other than LOS alone. Conclusion Antihypertensive therapy with a single tablet formulation of LOS/HCTZ is considered to be a useful option for controlling both BP and sUA, especially in uncontrolled hypertensive patients with hyperuricemia.