Heart failure & cardiomyopathiesRandomised controlled trial
Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients With Heart Failure
- Randomised controlled trial
- double-blind
- randomized-withdrawal
- open-label run-in
Authors' conclusion
In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalemia and down-titration/discontinuation of spironolactone.
Study context
- Population
- Heart failure and reduced ejection fraction (HFrEF) (NYHA II–IV; LVEF ≤40%) on optimal guideline-directed therapy (except mineralocorticoid receptor antagonists (MRA)) with prevalent or incident MRA-induced hyperkalemia, normokalemic on sodium zirconium cyclosilicate (SZC) and spironolactone ≥25 mg/day after run-inrandomized
- Participants
- 203 participants
- Comparison
- SZC vs placebo during spironolactone optimization
- SZCn = 102
- Placebon = 101reference
- Primary endpoint
- Optimal treatment response (normokalemia on spironolactone ≥25 mg/day without rescue therapy for hyperkalemia)
- Follow-up
- Months 1-6
Primary result
As reported in the abstract
Odds ratio
4.45
95% CI 2.89–6.86
P < 0.001
By group
SZC vs Placebo
OR 4.45 (95% CI 2.89–6.86); P < 0.001
Secondary outcomes
| Outcome | SZC | Placebo | Estimate | P value | |
|---|---|---|---|---|---|
| Normokalemia on randomisation dose of spironolactone without rescue therapy · hierarchically tested secondary endpoint | 58% | 23% | OR 4.58 (95% CI 2.78–7.55) | P < 0.001 | |
| Receiving spironolactone ≥25 mg/day | 81% | 50% | OR 4.33 (95% CI 2.50–7.52) | P < 0.001 | |
| Time to hyperkalemia | HR 0.51 (95% CI 0.37–0.71) | P < 0.001 | |||
| Time to decrease/discontinuation of spironolactone due to hyperkalemia | HR 0.37 (95% CI 0.17–0.73) | P = 0.006 | |||
| 0.10.31310Ratio (log scale) |
KCCQ Clinical Summary Score · 6 months
- No between-group difference in KCCQ-Clinical Summary Score at 6 months
- −1.01 points; 95% CI: −6.64 to 4.63; P = 0.72
Safety
Adverse events
Serious adverse events
Original publication
Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients With Heart Failure. J Am Coll Cardiol. Published 18 November 2024. doi:10.1016/j.jacc.2024.11.014
Summarised from the published abstract; every number is checked against it