In examining a subset from the African American Study of Kidney Disease and Hypertension (AASK), investigators determined that the beta-blocker metoprolol significantly increased serum uric acid (SUA) levels and risk of gout in black patients with chronic kidney disease (CKD) secondary to hypertension compared with the angiotensin-converting enzyme inhibitor ramipril and the calcium channel blocker amlodipine.  These findings were recently reported in the American Journal of Hypertension.

There is considerable comorbidity among hyperuricemia, hypertension, and CKD. As little guidance exists for clinicians when choosing antihypertensive agents in patients with these conditions, the authors sought to assess the impact of 3 medications on SUA, gout-related hospitalization, and use of gout-related medications (allopurinol, colchicine, or probenecid). The goal was to determine the best therapeutic choice in terms of lowering SUA levels and minimizing gout risk.

A total of 630 subjects (40% women, mean age 55 years) began the AASK trial with a mean SUA level of 8.2 mg/dL (standard deviation [SD], 2.0) and a mean serum creatinine level of 1.8 mg/dL (SD, 0.6). Serum chemistries were assessed again at 12 months and were compared with baseline (by medication assignment) using 2-sided t-tests.


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Metoprolol resulted in a 0.3-mg/dL (SD, 2.2) elevation in SUA level at 12 months compared with baseline; neither of the other medications increased SUA levels. The 12-month SUA for metoprolol was significantly higher compared with ramipril (0.40 mg/dL; 95% CI: 0.10-0.70; P =.009) or amlodipine (0.57 mg/dL; 95% CI: 0.18-0.95; P =.004). In contrast, no difference in SUA existed between ramipril and amlodipine on direct comparison (0.17 mg/dL; 95% CI: -0.21 to 0.55; P =.39).

Metoprolol displayed a nonsignificant association with increased risk for gout-related hospitalization (hazard ratio: 3.87; 95% CI: 0.82, 18.26; P =.09) and a significant association with elevated gout-related medication use (odds ratio: 1.62; 95% CI: 1.03-2.54; P =.04) when compared with ramipril. No difference existed between metoprolol and amlodipine in terms of gout-related hospitalization (P =.93) or gout-related medication use (P =.86). Additionally, comparing ramipril directly with amlodipine revealed no statistical difference in gout-related hospitalization (P =.32) or gout-related medication use (P =.14).

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Several limitations were acknowledged for this study. The sample size was underpowered regarding gout-related hospitalizations; there was no formal mechanism for flare detection; colchicine is not gout-specific; the study population lacked diversity; and urate-lowering medications may have skewed interpretation of the antihypertensive impact on SUA.

However, the authors also indicated several strengths. The study involved African Americans, a group often underrepresented in trials; a high-quality randomized design was utilized; and the availability of extensive records and long-term follow-up from the original AASK trial strengthened the trial results.

This analysis of antihypertensive influence on SUA in the face of CKD is supported by considerable prior research regarding beta-blockers vs angiotensin-converting enzyme inhibitors or calcium channel blockers. In light of current and previous findings, the researchers concluded: “…efforts to lower SUA and prevent gout should include avoidance of metoprolol, at least in patients with chronic kidney disease attributed to hypertension.”

Reference

Juraschek SP, Appel LJ, Miller ER III. Metoprolol increases uric acid and risk of gout in African Americans with chronic kidney disease attributed to hypertension. Am J Hypertens. 2017;30(9):871-875.