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 < 0.001]. Risk of hyperkalemia >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).

Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure.

AIMS: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF. METHODS: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100-299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes. CONCLUSION: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF.