March 1, 2025ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam)9 citationsOpen Access
Macitentan for Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Pulmonary Vascular Disease: Results of the SERENADE Randomized Clinical Trial and Open-Label Extension Study
Key Result
Macitentan did not lower NT-proBNP (P=0.24) or improve outcomes in heart failure with preserved/mildly reduced ejection fraction, but increased fluid retention (23% vs 14% with placebo).
Study Design
Type
RCT
Blinding
Double-blind
Multicenter
Yes
Structured PICO
Does macitentan improve NT-proBNP in patients with HF, LVEF ≥40%, and pulmonary vascular disease?
P
Population
Patients with heart failure (HF), left ventricular ejection fraction ≥40%, and pulmonary vascular disease who did not exhibit fluid retention after a 4-week placebo run-in and 5-week single-blind macitentan run-in.
I
Intervention
Macitentan
C
Comparator
Placebo
O
Outcome
Change in NT-proBNP (N-terminal pro-B-type natriuretic peptide; baseline to 24 weeks)surrogate
Macitentan did not improve NT-proBNP or clinical outcomes in patients with HFpEF/HFmrEF and pulmonary vascular disease, and increased fluid retention despite a run-in phase designed to exclude susceptible patients.
Main Result
p-value: p=0.24
Abstract
BACKGROUND: Despite favorable hemodynamic and neurohormonal effects, endothelin receptor antagonists have not improved outcomes in patients with heart failure (HF), possibly because they cause fluid retention. METHODS: In this randomized, double-blind, multicenter trial (SERENADE Macitentan in Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease), we evaluated the effects of an endothelin receptor antagonist, macitentan, in patients with HF, left ventricular ejection fraction ≥40%, and pulmonary vascular disease. After a 4-week placebo run-in (to ensure clinical stability), followed by a 5-week single-blind macitentan run-in, patients who did not exhibit fluid retention were randomized to macitentan or placebo. The primary end point was change in NT-proBNP (N-terminal pro-B-type natriuretic peptide; baseline to 24 weeks); secondary end points included change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score (baseline to 24 weeks) and time to worsening HF by 52 weeks. RESULTS: =0.24). More macitentan-treated patients developed fluid retention (16 23% versus 10 14%) and cardiac adverse events (33 46% versus 22 31%) versus placebo. CONCLUSIONS: Despite a novel enrichment trial design to target pulmonary vascular disease and exclude treatment-related fluid retention in patients with HF and preserved/mildly reduced left ventricular ejection fraction, macitentan neither lowered NT-proBNP nor improved HF outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03153111 and NCT03714815.