High- versus low-dose losartan and uric acid: An analysis from HEAAL.

BACKGROUND:Serum uric acid (SUA) is activated in catabolic, hypoxic, and inflammatory conditions characteristic of heart failure (HF) and is a source of reactive oxygen species. Losartan is unique among other angiotensin receptor blockers in reducing SUA. OBJECTIVES:To study the patient characteristics and outcome associations by SUA levels, as well as the effect of high- vs. low-dose losartan on SUA levels in HF. METHODS:HEAAL was a double-blind trial, comparing the effect of two doses of losartan 150 (high dose) vs. 50 (low dose) mg/day among 3834 patients with symptomatic HF, a left ventricular ejection fraction≤40 %, and known intolerance to angiotensin-converting enzyme inhibitors. In the present study, we studied the associations of SUA with outcomes and the effect of high- vs. low-dose losartan on SUA levels, incident hyperuricemia, and gout. RESULTS:Patients with higher SUA had more comorbidities, worse renal function, were more symptomatic, used diuretics more frequently, and were 1.5- to 2-fold more likely to experience HF hospitalizations and cardiovascular death. The benefit of high-dose losartan to improve HF outcomes was not influenced by baseline SUA levels (interaction p > 0.1). Compared with low-dose, high-dose losartan reduced SUA by -0.27 (-0.34 to -0.21) mg/dL, p < 0.001. The incidence of hyperuricemia was reduced with high-dose losartan, but the incidence of gout was not. CONCLUSIONS:In HEAAL, hyperuricemia was associated with worse outcomes. High-dose losartan reduced SUA and hyperuricemia more than low-dose and the cardiovascular benefits of high-dose losartan were not modified by SUA levels.