Cardiovascular Safety of Febuxostat in Patients With Gout or Hyperuricemia: A Systematic Review of Randomized Controlled Trials

 Clin Rheumatol. 2023 Dec 20. doi: 10.1097/RHU.0000000000002045. Online ahead of print.


Roba Ghossan 1Ouidade Aitisha Tabesh 2Fouad Fayad 2Pascal Richette 3Thomas Bardin 4


Author information

1From the Rheumatology Department, Cochin University Hospital, Paris, France.

2Rheumatology Department, Hotel-Dieu de France University Hospital, Saint-Joseph University, Beirut, Lebanon.

3Rheumatology Department, Lariboisière University Hospital.

4Université Paris Cité, Paris, France.


Introduction: To this date, a causal relationship between febuxostat and cardiovascular disease remains controversial as comparison between trials can be challenging and may lead to misleading conclusions, especially when facing heterogeneous cardiovascular outcomes. We aimed to compare the cardiovascular outcomes in the most pertinent trials of febuxostat compared with controls.

Methods: We searched electronic databases using a PICOS-style approach search strategy of randomized controlled trials (RCTs) on cardiovascular outcomes of febuxostat in patients with gout or hyperuricemia. We conducted a quality and risk of bias assessment of the included clinical trials. The definition of major adverse cardiovascular event as well as all reported cardiovascular outcomes were retrieved from every involved trial.

Results: Of the 1173 records identified from all sources, 20 RCTs were included in the analysis. The mean duration of follow-up was 69.7 ± 81.5 weeks, and febuxostat dose ranged from 10 to 240 mg with 80 mg being the most commonly used dosage. Overall, the quality of evidence deriving from all RCTs showed concerns in most studies (65%). Major adverse cardiovascular event was defined in 7 of the 20 RCTs (35%), and cardiovascular outcome reporting was very heterogeneous. Overall, the data of cardiovascular safety of febuxostat were reassuring.

Conclusions: Our systematic review showed high level of concerns in quality assessment domains as well heterogeneous cardiovascular outcomes across included studies. Cardiovascular outcomes in the majority of White males with gout treated with febuxostat were reassuring when compared with allopurinol. Further studies are needed to draw conclusions in patients with severe cardiovascular disease.

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