Key result
Losartan-induced uric acid reduction linked to ~5% lower cardiovascular risk per 0.5 mg/dl decrement.
Why the study?
Whether reductions in serum uric acid during angiotensin receptor blocker therapy are associated with cardiovascular protection was unclear.
Observational
Effect estimate: 5.3% risk reduction per 0.5 mg/dl decrement in SUA (95% CI 0.9-9.9)
p-value: p=0.017
SUA reduction with losartan was associated with lower CV risk in diabetic nephropathy; leaves open whether targeting SUA improves outcomes prospectively.
OBJECTIVE: Increased levels of serum uric acid (SUA) are thought to be an independent risk marker for cardiovascular complications. Treatment with the angiotensin receptor blocker (ARB) losartan lowers SUA in contrast to other ARBs. Whether reductions in SUA during ARB therapy are associated with cardiovascular protection is unclear. We aimed to investigate this. METHOD: In a post-hoc analysis of the Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy (IDNT) trials we determined whether the short-term effect of losartan and of irbesartan on SUA is related with long-term cardiovascular outcome by means of Cox regression. RESULTS: Compared to placebo, losartan significantly changed SUA [-0.16 mg/dl; 95% confidence interval (CI) -0.01 to -0.30; P = 0.031], whereas irbesartan did not (-0.09 mg/dl; (95% CI 0.09 to -0.28; P = 0.30). Each 0.5 mg/dl decrement in SUA during losartan treatment in the first 6 months resulted in a reduction in the risk of cardiovascular outcomes by 5.3% (95% CI 0.9 to 9.9; P = 0.017). Losartan reduced the risk of cardiovascular outcomes by 9.2% (95% CI -7.9 to 23.6). Adjustment for the 6-month change in SUA attenuated the treatment effect to 4.6% (95% CI -16.2 to 22.0), suggesting that part of the cardiovascular protective effect of losartan is attributable to its short-term effect on SUA. CONCLUSION: Losartan but not irbesartan significantly lowers SUA compared to placebo in patients with type 2 diabetes and nephropathy. The degree of reduction in SUA explains part of the cardiovascular effect of losartan. This supports the hypothesis that SUA is a modifiable risk factor for cardiovascular disease, at least in type 2 diabetics with nephropathy.
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Smink et al. (2012) conducted an observational in Type 2 diabetes and nephropathy. Losartan vs. Placebo or Irbesartan was evaluated on Cardiovascular outcomes (5.3% risk reduction per 0.5 mg/dl decrement in SUA, 95% CI 0.9-9.9, p=0.017). Each 0.5 mg/dl decrement in serum uric acid during the first 6 months of losartan treatment was associated with a 5.3% reduction in the risk of cardiovascular outcomes (95% CI 0.9-9.9; P=0.017).
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