Background/Purpose: A recent study showed that febuxostat had a higher risk of cardiovascular and all-cause mortality than allopurinol. Because febuxostat is more potent than allopurinol, we hypothesized that an abrupt change in serum uric acid levels caused by urate-lowering agent might influence the risk of cardiovascular events.

Methods: We included patients with cardiovascular disease (CVD) treated with allopurinol or febuxostat. Cardiovascular events were defined as follows: nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring coronary revascularization procedure, and cardiovascular death. The change in serum uric acid level was determined by the difference or reduction rate in uric acid within 6 months after exposure to allopurinol or febuxostat. The factors associated with cardiovascular events were evaluated by Cox regression analysis.

Results: In total, 207 patients with CVD exposed to allopurinol or febuxostat were included. Cardiovascular events occurred in 25 patients (12.1%). In univariate analysis, hypertension, difference in uric acid levels between baseline and post-exposure to urate-lowering agent, and reduction rate in uric acid levels were associated with cardiovascular events. In multivariate analysis, hypertension [hazard ratio (HR) 3.450, 95% confidence interval (CI), 1.167–10.202, p = 0.025] and reduction rate in uric acid to the lowest levels (HR 26.133, CI, 6.876–99.319, p < 0.001) were associated with cardiovascular events.

Conclusion: Rapid reduction in serum uric acid levels was associated with the recurrence of cardiovascular events in patients with CVD. Thus, careful attention should be paid to abruptly changed serum uric acid levels after treating urate lowering agent in high-risk CVD patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rapid-reduction-in-uric-acid-is-associated-with-recurrent-cardiovascular-events/