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SAT0105 Losartan but not irbesartan reduces serum uric acid in hypertensive patients with gout
  1. G Wuerzner,
  2. A Chioléro,
  3. M Maillard,
  4. CL Stubi-Fallab,
  5. M Burnier,
  6. CA Gerster
  1. Hypertension, Lausanne University Hospital, Lausanne, Switzerland

Abstract

Background Losartan is the only angiotensin II receptor antagonist with uricosuric properties and has been shown to decrease serum uric acid (SUA) levels in normal subjects as well as in hypertensive patients.

Objectives To assess and to compare the effects of losartan and irbesartan on serum uric acid in hypertensive patients with gout.

Methods Prospective, randomised, double-blind, cross-over study preceded by a three weeks run-in period with enalapril 20 mg od. During the first four weeks, patients received a morning dose of either losartan 50 mg or irbesartan 150 mg and a evening dose of placebo. The dose was than increased to losartan 50 mg bid or irbesartan bid. The losartan and the irbesartan phases were separated by three weeks of treatment with enalapril 20 mg od.

All drugs were provided in an electronic pill container allowing to monitor compliance (MEMS system).

Results Thirteen male hypertensive (office blood pressure > 140/90 mmHg or under antihypertensive therapy) and hyperuricemic (SUA over 420 μmol/L or over 7.1 g/dL, without any hypouricemic agents) patients completed this study.

The changes in blood pressure induced by losartan and irbesartan were comparable. In contrast to irbesartan which had no effect on SUA, losartan (50 mg od) decreased SUA significantly from 538 ± 26 μmol/L to 491 ± 20 μmol/L (p < 0.01) and to 484 ± 25 μmol/L at 50 mg bid. During the first 4 h after drug intake, the first dose of losartan increased the urinary uric acid/creatinine ratio when compared with irbesartan (0.525 ± 0.071 vs 0.358 ± 0.045, p = 0.019). This increase was still present at week 4 (0.485 ± 0.085 vs 0.331 ± 0.057, p < 0.01) but was not found at week 8 when patients received a bid regimen (0.316 ± 0.043 vs 0.331 ± 0.029, p = ns). The frequency of acute gout episods did not differ between treatments. The monitoring of compliance showed that the adherence to the morning dose was good (89.2 ± 2.8%) and significantly greater than that to the evening dose (78.9 ± 3.1%, p < 0.001).

Conclusion These results demonstrate the potential benefits of using losartan in hypertensive patients with hyperuricemia and gout. They also suggest that losartan-treated patients reach a new uric acid steady-state during a sustained administration (>1 month). Hence, the uricosuric effect tends to decrease with time as SUA is reduced. Increasing the dose of losartan to 50 mg bid does not appear to induce a further decrease in serum uric acid.

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