2 research outputs found
Patiromer for the management of hyperkalaemia in patients receiving renin-angiotensin-aldosterone system inhibitors for heart failure: design and rationale of the DIAMOND trial
Aims In patients with current or a history of hyperkalaemia, treatment
with renin-angiotensin-aldosterone system inhibitors (RAASi) is often
compromised. Patiromer, a novel potassium (K+) binder, may improve serum
K+ levels and adherence to RAASi. Methods The DIAMOND trial will enroll
similar to 820 patients with heart failure with reduced ejection
fraction (HFrEF; ejection fraction <= 40%). Patients meeting the
screening criteria will enter a single-blinded run-in phase where they
will be started or continued on a mineralocorticoid receptor antagonist
(MRA) titrated to 50 mg/day and other RAASi therapy to >= 50% target
dose, and patiromer. Patiromer will be titrated up to a maximum three
packs/day (8.4 g/pack) to achieve optimal doses of RAASi without
hyperkalaemia. The run-in phase will last up to 12 weeks, following
which patients will undergo double-blind randomization in a 1:1 ratio to
receive either continued patiromer or placebo (patiromer withdrawal).
The primary endpoint is the mean difference in serum K+ from
randomization between patiromer and placebo arms. Secondary endpoints
will include hyperkalaemia events with K+ value >5.5 mEq/L, durable
enablement of MRA at target dose, investigator-reported adverse events
of hyperkalaemia, hyperkalaemia-related clinical endpoints and an
overall RAASi use score (using a 0-8-point scale) comprising all-cause
death, occurrence of cardiovascular hospitalization or usage of
comprehensive heart failure medication. Conclusion The DIAMOND trial is
designed to determine if patiromer can favourably impact K+ control in
patients with HFrEF with hyperkalaemia or a history of hyperkalaemia
leading to RAASi therapy compromise, and in turn improve RAASi use
Patiromer for the management of hyperkalemia in heart failure with reduced ejection fraction: the DIAMOND trial
Aims To investigate the impact of patiromer on the serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of the RAASi therapy [>= 50% recommended dose of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist (MRA) spironolactone or eplerenone]. Specified target doses of the RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in the adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13-43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: -0.10 mmol/l (95% confidence interval, CI -0.13, 0.07); P 5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P < 0.001) and total RAASi use score (win ratio 1.25, P = 0.048) favored the patiromer arm. Adverse events were similar between groups. Conclusion Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066)