Cardiovascular Safety of Febuxostat vs. Allopurinol in Gout Patients with Cardiovascular Diseases: A Target Trial...

Area of Science:

• Cardiology
• Rheumatology
• Pharmacovigilance

Background:

• Gout management guidelines recommend febuxostat and allopurinol as first-line urate-lowering therapies (ULTs).
• Cardiovascular safety concerns for febuxostat persist due to conflicting trial data and limited real-world evidence in high-risk populations.
• Existing evidence is insufficient for patients with pre-existing cardiovascular disease (CVD).

Purpose of the Study:

• To evaluate the long-term cardiovascular safety of febuxostat compared to allopurinol.
• To assess risks in gout patients with pre-existing cardiovascular disease (CVD).
• To provide real-world evidence for personalized prescribing decisions.

Main Methods:

• Target trial emulation study using US collaborative electronic health records.
• Included 7555 propensity-score matched pairs of adults aged ≥50 years initiating febuxostat or allopurinol.
• Primary outcome: Major adverse cardiovascular events (MACE); Secondary outcome: All-cause mortality over a 10-year follow-up.

Main Results:

• No significant difference in MACE risk between febuxostat and allopurinol (HR: 1.027; 95% CI: 0.978-1.079).
• Febuxostat was associated with a modest increase in all-cause mortality (HR: 1.125; 95% CI: 1.039-1.217).
• Risk elevations for mortality were consistent across subgroups, including race and lifestyle factors.

Conclusions:

• Febuxostat use in gout patients with pre-existing CVD showed comparable MACE risk but a trend towards increased all-cause mortality versus allopurinol.
• Findings suggest a need for cautious febuxostat prescribing in this high-risk population.
• Personalized prescribing considering patient-specific factors like race and lifestyle is recommended.