Effects of serelaxin in patients with acute heart failure

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. Results: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. Conclusions: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778. opens in new tab.

Patiromer for the management of hyperkalaemia in patients receiving renin- angiotensin- aldosterone system inhibitors for heart failure: design and rationale of the DIAMOND trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171557/1/ejhf2386_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171557/2/ejhf2386.pd

Patiromer for the management of hyperkalaemia in patients receiving renin- angiotensin- aldosterone system inhibitors for heart failure: design and rationale of the DIAMOND trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171557/1/ejhf2386_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171557/2/ejhf2386.pd

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)

Patiromer for the management of hyperkalemia in heart failure with reduced ejection fraction: the DIAMOND trial

Aims: To investigate the impact of patiromer on 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 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 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 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 adjusted mean change between patiromer and placebo: -0.10 [95% confidence interval, CI -0.13, -0.07] mmol/L, P&lt;0.001). Risk of hyperkalemia &gt;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&lt;0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P&lt;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)