Effect of sacubitril/valsartan on serum uric acid and blood pressure in patients with hypertension and asymptomatic hyperuricemia: A randomized clinical trial.

Hyperuricemia commonly coexists with hypertension and is associated with increased renal and cardiovascular risk, yet few antihypertensive agents lower serum uric acid. This study compared the urate-lowering effects of sacubitril/valsartan versus valsartan in adults with primary hypertension and asymptomatic hyperuricemia. This single-center, prospective, randomized, open-label clinical trial enrolled adults with mild-to-moderate primary hypertension and fasting serum uric acid ≥ 420 μmol/L from September 2021 to December 2024, with 12 weeks of follow-up. Participants were randomized 1:1 to sacubitril/valsartan 200 mg once daily or valsartan 160 mg once daily. A standardized stepwise add-on protocol with amlodipine was used to achieve blood pressure control. The primary outcome was the change in fasting serum uric acid from baseline to week 12. In the primary intention-to-treat analysis using multiple imputation, treatment-effect estimates were pooled across imputed datasets using Rubin's rules. In the fully adjusted model, sacubitril/valsartan was associated with a greater reduction in serum uric acid at week 12 than valsartan (β = 30.13 μmol/L; 95% CI, 4.33-55.92; P = 0.022). Similar findings were observed in the per-protocol analysis. Blood pressure control at week 12 was comparable between treatment groups, although more participants assigned to valsartan required escalation to amlodipine 10 mg than those assigned to sacubitril/valsartan (17/75 [22.67%] vs. 4/75 [5.33%]; P = 0.008). In adults with primary hypertension and asymptomatic hyperuricemia, sacubitril/valsartan was associated with greater serum uric acid reduction than valsartan over 12 weeks while achieving comparable blood pressure control. These findings suggest that sacubitril/valsartan may have a favorable uric acid profile among hypertensive patients with asymptomatic hyperuricemia. Trial Registration Chinese Clinical Trial Registry: ChiCTR2100050320 ( https://www.chictr.org.cn ). Date of Registration: September 1, 2021.