Heart failure & cardiomyopathies
Verinurad Plus Allopurinol for Heart Failure With Preserved Ejection Fraction: The AMETHYST Randomized Clinical Trial
Authors' conclusion
Results of this randomized clinical trial show that despite substantial SUA lowering, verinurad plus allopurinol did not result in a significant improvement in peak VO2 or symptoms compared with allopurinol monotherapy or placebo in HFpEF.
Study context
- Population
- Patients ≥40 years with heart failure with preserved ejection fraction (HFpEF) and serum uric acid (SUA) >6 mg/dLrandomised
- Participants
- 159 patients
- Comparison
- Verinurad plus allopurinol vs allopurinol monotherapy vs placebo
- Verinurad plus allopurinoln = 53
- Allopurinoln = 53
- Placebon = 53reference
- Primary endpoint
- Key end points: changes in peak VO2, KCCQ-TSS and SUA level
- Follow-up
- Baseline to week 32
Methodological detailsphase 2, double-blind, 59 centres in 12 countries, All patients received oral colchicine 0.5 to 0.6 mg daily for the first 12 weeks
- Phase 2
- Double-blind
- 59 centres in 12 countries
- All patients received oral colchicine 0.5 to 0.6 mg daily for the first 12 weeks
Primary result
As reported in the abstract
week 32
| Group | Value | Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) change | SUA mean change |
|---|---|---|---|
| Verinurad plus allopurinol | change 0.27 (95% CI −0.56–1.10) mL/kg/min | 4.3 (95% CI, 0.3-8.3) | −59.6% (95% CI, −64.4% to −54.2%) |
| Allopurinol | change −0.17 (95% CI −1.03–0.69) mL/kg/min | 4.5 (95% CI, 0.3-8.6) | −37.6% (95% CI, −45.3% to −28.9%) |
| Placebo | change 0.37 (95% CI −0.45–1.19) mL/kg/min | 1.2 (95% CI, −3.0 to 5.3) | 0.8% (95% CI, −11.8% to 15.2%) |
Value
Verinurad plus allopurinolchange 0.27 (95% CI −0.56–1.10) mL/kg/min
Allopurinolchange −0.17 (95% CI −1.03–0.69) mL/kg/min
Placebochange 0.37 (95% CI −0.45–1.19) mL/kg/min
Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) change
Verinurad plus allopurinol4.3 (95% CI, 0.3-8.3)
Allopurinol4.5 (95% CI, 0.3-8.6)
Placebo1.2 (95% CI, −3.0 to 5.3)
SUA mean change
Verinurad plus allopurinol−59.6% (95% CI, −64.4% to −54.2%)
Allopurinol−37.6% (95% CI, −45.3% to −28.9%)
Placebo0.8% (95% CI, −11.8% to 15.2%)
- Verinurad plus allopurinol lowered SUA more than allopurinol or placebo
- P < 0.001
Further findings
Deaths or CV events
Deaths or CV events
- No adverse safety signals
Original publication
Verinurad Plus Allopurinol for Heart Failure With Preserved Ejection Fraction: The AMETHYST Randomized Clinical Trial. JAMA Cardiol. Published 1 October 2024. doi:10.
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