부산대학교 도서관

Introduction: Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that improves cardiac function without direct vascular or neurohormonal effects. Improvement in NT-proBNP, a marker of ventricular wall stress, has been related to increased survival in patients with chronic heart failure with reduced ejection fraction (HFrEF).Hypothesis: We hypothesized that increases in cardiac function with chronic use of OM improves the number of patients with HFrEF achieving at least a 30% reduction in NT-proBNP.Methods: COSMIC-HF (NCT 01786512) was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial in outpatients (n=448) with a history of optimally-treated chronic HF, LVEF ≤40%, and NT-proBNP ≥200 pg/mL (≥1200 pg/mL with atrial fibrillation). In the expansion phase, patients were randomized 1:1:1 to receive placebo BID (n=149), OM 25 mg BID (n=150), or 25 mg BID with pharmacokinetic-guided increases to 50 mg BID (n=146; OM PK-group) for 20 weeks. In a post-hoc analysis, we assessed percent changes in NT-proBNP between the placebo and OM PK-group from baseline to week 20.Results: Patients were 63±11 years old, predominantly male (82%), with LVEF of 29±7%, and elevated NT-proBNP at baseline [placebo: 1719 pg/mL (median; Q1, Q3: 699, 3242); OM PK-group: 1733 (Q1, Q3: 881, 3151)]. There were no differences between the placebo and PK group at baseline. Compared to placebo, more patients in the OM PK-group had reductions in NT-proBNP when assessed by percent change from baseline (Figure; Chi-square, nominal p-values).Conclusion: In patients with HFrEF, more patients had a potentially clinically-meaningful reduction in NT-proBNP in the OM PK-group compared to placebo. Given the absence of any direct effect on neurohormones, preload or afterload by OM, these results suggest that OM was able to reduce myocardial wall stress, possibly contributing to the observed beneficial ventricular remodeling.