Does Uloric Increase Heart Risks?
Uloric (febuxostat), a gout treatment that lowers uric acid, carries a boxed warning from the FDA for heightened cardiovascular death risk compared to allopurinol, another gout drug. This stems from the CARES trial, where Uloric showed a 34% higher rate of heart-related deaths (4.3% vs. 3.2%) in patients with gout and cardiovascular disease, though overall mortality was similar.[1][2]
What the CARES Trial Found
The 2018 CARES study followed 6,190 patients for up to 5 years. Key results:
- Cardiovascular death: 134 on Uloric vs. 111 on allopurinol (hazard ratio 1.34).
- No difference in nonfatal heart events like stroke or heart attack.
- Trial focused on high-risk patients (established cardiovascular disease), so risks may differ for others.[3][4]
FDA approved Uloric in 2009 but added the warning in 2019 after CARES data review, restricting use to patients intolerant to allopurinol or for whom it fails.[1]
Other Heart-Related Concerns
Post-marketing reports and studies note:
- Increased reports of heart failure, atrial fibrillation, and sudden cardiac death with Uloric vs. allopurinol.
- A 2020 FAST trial in Europe found no overall CV mortality difference but higher cardiac deaths in Uloric's high-dose group.
- No causal proof beyond CARES; mechanisms unclear, possibly tied to urate-lowering effects or patient factors.[2][5]
Who Faces Higher Risks?
Primarily patients with existing heart disease. Label advises monitoring those with cardiovascular risks and avoiding first-line use. Gout itself raises heart risks, complicating attribution.[1][6]
Alternatives and What Doctors Recommend
Allopurinol remains first-line for most. Other options: probenecid, krystexxa (pegloticase) for refractory cases. Guidelines (ACR 2020) favor Uloric only if allopurinol unsuitable.[7]
| Drug | CV Death Risk vs. Uloric | Common Use |
|------|---------------------------|------------|
| Allopurinol | Lower (per CARES) | First-line |
| Krystexxa | Limited data; infusions needed | Severe gout |
| Probenecid | No boxed warning | Mild gout |
Ongoing Monitoring and Lawsuits
Takeda (Uloric's maker) faces lawsuits alleging downplayed risks. FDA requires CV outcome trials for new gout drugs post-Cares. Recent data (2023) shows Uloric prescriptions dropped 50% since warning.[8]
Sources
[1]: FDA Uloric Label
[2]: FDA Warning Announcement
[3]: NEJM CARES Trial
[4]: CARES Study Summary
[5]: FAST Trial Lancet
[6]: ACR Gout Guidelines
[7]: Drugs.com Uloric Alternatives
[8]: DrugPatentWatch Uloric