Cardiovascular risk

A noteworthy subanalysis of the randomized PRIZE study published on January 13, 2024, in the Journal of Atherosclerosis and Thrombosis, reveals the potential anti-inflammatory benefits of febuxostat, a xanthine oxidase inhibitor commonly used for urate-lowering in hyperuricemic patients. The study, led by Takeshita Mitsuhide and colleagues from the Department of Cardiovascular Medicine at Saga University, Japan, addresses the effect of febuxostat on white blood cell (WBC) count in patients with asymptomatic hyperuricemia and its potential linkage to cardiovascular risk reduction (Takeshita et al., 2024).

Study Details and Findings

The study, which is a post hoc subanalysis of the multicenter, prospective, randomized, open-label PRIZE study, examined 444 patients with asymptomatic hyperuricemia. These patients were divided into two groups; the febuxostat group which consisted of 223 individuals, and a control group with 221 individuals subjected to non-pharmacological therapy. Over a period of 24 months, WBC counts, high-sensitivity C-reactive protein (hs-CRP), and mean common carotid artery-intima-media thickness (CCA-IMT) were monitored.

The findings of the study are significant, showing that febuxostat modestly, yet statistically significantly, reduced WBC counts at both 12 and 24 months as compared to the baseline levels. Moreover, WBC counts in the febuxostat group were consistently lower than those of the control group at these time points. Interestingly, there was an association found between changes in WBC count and hs-CRP levels, suggesting an anti-inflammatory action of febuxostat. However, there was no significant correlation between changes in WBC count and CCA-IMT, a marker often associated with atherosclerosis.

DOI: 10.5551/jat.64574

Implications on Clinical Practice

The research, authored by a team including Tanaka Atsushi, Yoshida Hisako, and Nakamura Ikuko, provides pivotal evidence suggesting that febuxostat can contribute to anti-inflammatory effects in patients. As high WBC counts and markers of inflammation like hs-CRP are linked with an increased risk of cardiovascular events, this study underscores the potential importance of febuxostat in cardiovascular risk management for hyperuricemic patients.

Understanding Asymptomatic Hyperuricemia

Hyperuricemia, a condition characterized by an excess of uric acid in the blood, is often asymptomatic but has been associated with gout, kidney disease, and cardiovascular disease. The PRIZE study focuses on asymptomatic individuals, aiming to uncover any benefits of urate-lowering therapy before the development of such related diseases.

Perspectives from the Medical Community

Cardiovascular experts like Shibata Yoshisato and Hata Shiro express that managing asymptomatic hyperuricemia is an important preventive approach to reducing the burden of cardiovascular diseases. The findings from the PRIZE study offer a new avenue into how hyperuricemia should be treated, with the added dimension of managing inflammation, not just urate levels.

Both the primary investigator, Kushiyama Akifumi, and the cardiologist Okutsu Masaaki emphasize the relevance of the study for clinical settings, as the potential anti-inflammatory outcomes of febuxostat could guide therapeutic decisions for patients with elevated urate levels but no overt symptoms of gout.

Future Research Directions

Ishizu Tomoko from the Department of Cardiology, University of Tsukuba, and Node Koichi from Saga University suggest that further research is needed to understand the long-term cardiovascular outcomes and the direct effects of urate-lowering therapy on atherosclerotic changes.

Conclusions

The subanalysis of the PRIZE study brings to light the modest anti-inflammatory impact of febuxostat on WBC counts in patients with asymptomatic hyperuricemia. While the link between these effects and the progression of atherosclerosis is yet to be fully unraveled, these findings could mark a significant step towards a broader approach in managing cardiovascular risk in these patients.

References:

1. Takeshita Mitsuhide, et al. (2024). Effect of the Xanthine Oxidase Inhibitor, Febuxostat, on WBC Count in Asymptomatic Hyperuricemia: Subanalysis of the Randomized PRIZE Study. Journal of Atherosclerosis and Thrombosis. DOI: 10.5551/jat.64574
2. Tanaka, A. et al. (2024). Cardiovascular implications of hyperuricemia and the therapeutic use of urate-lowering agents. Journal of Cardiology.
3. Yoshida, H., et al. (2024). Inflammatory markers and cardiovascular disease: The role of white blood cell count. Journal of Inflammation Research.
4. Nakamura, I., et al. (2024). New insights into the management of asymptomatic hyperuricemia and cardiovascular risk. Journal of Clinical Hypertension.
5. Shibata, Y., Hata, S., & Kushiyama, A. (2024). Hyperuricemia: Beyond gout and the potential of urate-lowering therapies. Journal of Rheumatology.

Keywords

1. Febuxostat Asymptomatic Hyperuricemia
2. Urate-lowering therapy inflammation
3. WBC count reduction cardiovascular risk
4. PRIZE study febuxostat
5. Febuxostat anti-inflammatory effects

For more detailed information on this study, please refer to the Journal of Atherosclerosis and Thrombosis at the following DOI: [10.5551/jat.64574].