The Effect of Omecamtiv Mecarbil in Hospitalized Patients as Compared With Outpatients With HFrEF: An Analysis of GALACTIC-HF.

Background: In the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial, omecamtiv mecarbil, compared with placebo, reduced the risk of worsening heart failure (HF) events, or cardiovascular death in patients with HF and reduced ejection fraction. The primary aim of this prespecified analysis was to evaluate the safety and efficacy of omecamtiv mecarbil by randomization setting, that is, whether participants were enrolled as outpatients or inpatients.

Methods And Results: Patients were randomized either during a HF hospitalization or as an outpatient, within one year of a worsening HF event (hospitalization or emergency department visit).

Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE.

Background: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease. However, the optimal achieved LDL-C level with regard to efficacy and safety in the long term remains unknown.

Methods: In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), 27 564 patients with stable atherosclerotic cardiovascular disease were randomized to evolocumab versus placebo, with a median follow-up of 2.

Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease.

Background: In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular events and was safe and well tolerated over a median of 2.2 years of follow-up. However, large-scale, long-term data are lacking.

Effects of omecamtiv mecarbil in heart failure with reduced ejection fraction according to blood pressure: the GALACTIC-HF trial.

Aim: Patients with heart failure with reduced ejection fraction and low systolic blood pressure (SBP) have high mortality, hospitalizations, and poorly tolerate evidence-based medical treatment. Omecamtiv mecarbil may be particularly helpful in such patients. This study examined its efficacy and tolerability in patients with SBP ≤100 mmHg enrolled in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF).

A First-in-Human Study of AMG 986, a Novel Apelin Receptor Agonist, in Healthy Subjects and Heart Failure Patients.

Purpose: AMG 986 is a novel apelin receptor (APJ) agonist that improves cardiac contractility in animal models without adversely impacting hemodynamics. This phase 1b study evaluated the safety/tolerability, pharmacokinetics, and pharmacodynamics of AMG 986 in healthy subjects and patients with heart failure (HF).

Methods: Healthy adults (Parts A/B) and HF patients (Part C) aged 18-85 years were randomized 3:1 to single-dose oral/IV AMG 986 or placebo (Part A); multiple-dose oral/IV AMG 986 or placebo (Part B); or escalating-dose oral AMG 986 or placebo (Part C).

Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure: A Post Hoc Analysis of Data From the GALACTIC-HF Randomized Clinical Trial.

Importance: Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients' condition worsen over time despite treatment. Patients with more severe disease are often intolerant of available medical therapies.

Objective: To evaluate the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe heart failure (HF) enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial.

Pharmacokinetic Drug-Drug Interaction Study of Omecamtiv Mecarbil With Amiodarone and Digoxin in Healthy Subjects.

Omecamtiv mecarbil (OM), a novel cardiac myosin activator, is being evaluated for the treatment of heart failure with reduced ejection fraction. In vitro studies demonstrate OM as a substrate and inhibitor of P-glycoprotein (P-gp), which can result in drug-drug interactions. Two phase 1, open-label studies assessed the effect of coadministration of OM (50-mg single dose) on the pharmacokinetics of digoxin (0.

Evaluation of drug-drug interaction potential between omecamtiv mecarbil and rosuvastatin, a BCRP substrate, with a clinical study in healthy subjects and using a physiologically-based pharmacokinetic model.

Omecamtiv mecarbil (OM) is a novel cardiac myosin activator in development for the treatment of heart failure. In vitro, OM is an inhibitor of BCRP. Rosuvastatin, a BCRP substrate, is one of the most commonly prescribed medications in patients with heart failure.

Pharmacokinetics, Tolerability, and Safety of Single and Multiple Omecamtiv Mecarbil Doses in Healthy Japanese and Caucasian Subjects.

Background And Objectives: Omecamtiv mecarbil (OM) is a cardiac myosin activator under development for the treatment of heart failure. The pharmacokinetics of single and multiple doses of OM were investigated in healthy Japanese subjects in two clinical studies.

Methods: Study 1 (n = 36) evaluated the bioavailability and pharmacokinetics after intravenous infusion (15 mg/h for 4 h) and an oral modified release (MR) tablet in healthy Japanese and Caucasian subjects using 25 mg single and multiple doses and 50 mg single dose.

Pharmacokinetic Drug-Drug Interaction Study of Omecamtiv Mecarbil With Omeprazole, a Proton Pump Inhibitor, in Healthy Subjects.

Omecamtiv mecarbil (OM) is a novel cardiac myosin activator in development for the treatment of heart failure (HF) with reduced ejection fraction. OM is administered as a 25-, 37.5-, or 50-mg modified-release formulation in patients with HF.

Pharmacokinetic Evaluation of the CYP3A4 and CYP2D6 Drug-Drug Interaction and CYP3A4 Induction Potential of Omecamtiv Mecarbil: Two Open-Label Studies in Healthy Subjects.

Omecamtiv mecarbil (OM) is a cardiac myosin activator under development for the treatment of heart failure. The effect of CYP3A4 and CYP2D6 inhibition on OM pharmacokinetics and the potential for OM to induce CYP3A4 was assessed in 2 studies. Study 1, part A, assessed the effect of ketoconazole 200 mg on the pharmacokinetics of OM 10 mg in CYP2D6 extensive metabolizers (EMs; n = 8) or poor metabolizers (PMs; n = 8).

Omecamtiv mecarbil does not prolong QTc intervals at therapeutic concentrations.

Aims: Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator under investigation for the treatment of heart failure. This study aimed to evaluate the effect of therapeutic concentrations of OM on electrocardiogram (ECG) parameters and exclude a clinically concerning effect on the rate-corrected QT (QTc) interval.

Methods: In part A, 70 healthy subjects received a 25 mg oral dose of OM, and pharmacokinetics were assessed.

Effect of Varying Degrees of Hepatic Impairment on the Pharmacokinetics of Omecamtiv Mecarbil.

Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator under investigation for the treatment of heart failure with reduced ejection fraction. OM is primarily eliminated via metabolism mediated by multiple cytochrome P450 enzymes. This phase 1 single-dose, multicenter, open-label, nonrandomized study evaluated the pharmacokinetics (PK) of OM and major metabolites M3 and M4, safety, and tolerability following oral administration of a single dose of 25-mg MR tablet in subjects with mild (n = 6) or moderate (n = 6) hepatic impairment (according to Child-Pugh classification) versus subjects with normal hepatic function (n = 6).

Effect of Omecamtiv Mecarbil on the Pharmacokinetics of Metformin, a Probe Substrate for MATE1/MATE2-K, in Healthy Subjects.

Background And Objective: Omecamtiv mecarbil (OM) is a novel cardiac myosin activator in development for the treatment of heart failure with reduced ejection fraction. The objective of this study was to evaluate the potential for OM to affect the pharmacokinetics of metformin.

Methods: This was an open-label, fixed-sequence study in 14 healthy subjects.

Switchability and minimal effect of food on pharmacokinetics of modified release tablet strengths of omecamtiv mecarbil, a cardiac myosin activator.

Omecamtiv mecarbil (OM) is a cardiac myosin activator in clinical development for the treatment of heart failure. The effect of food on the pharmacokinetics (PK) of 25, 37.5, and 50 mg strength modified release (MR) tablets and the bioequivalence of two 25 mg tablets versus one 50 mg MR tablet were evaluated in two open-label, randomized, cross-over studies in healthy subjects.

Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF.

Background: In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (≤35%).

Objectives: The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.

Methods: Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.

Effect of Varying Degrees of Renal Impairment on the Pharmacokinetics of Omecamtiv Mecarbil.

Background And Objective: Omecamtiv mecarbil is a novel selective cardiac myosin activator (myotrope) under investigation for the treatment of heart failure with reduced ejection fraction. The objective of this clinical study was to estimate the effect of varying degrees of renal impairment on the pharmacokinetics of omecamtiv mecarbil single dose (50 mg) under fasted conditions.

Methods: This phase I, open-label, non-randomized, parallel-group study evaluated the pharmacokinetics, safety, and tolerability of a single oral dose of omecamtiv mecarbil 50 mg in individuals with normal renal function or mild, moderate, and severe renal impairment, including end-stage renal disease requiring dialysis.

The impact of heart failure on patients and caregivers: A qualitative study.

Background: Heart failure is rising in prevalence but relatively little is known about the experiences and journey of patients and their caregivers. The goal of this paper is to present the symptom and symptom impact experiences of patients with heart failure and their caregivers.

Methods: This was a United States-based study wherein in-person focus groups were conducted.

Association of plasma adiponectin with pulmonary hypertension, mortality and heart failure in African Americans: Jackson Heart Study.

Background: Adiponectin is a polypeptide hormone related to obesity, and a known modulator of pulmonary vascular remodeling. Association between plasma adiponectin levels and pulmonary hypertension (PH) has not been studied in African Americans (AAs) who are disproportionately affected by obesity. The relationship between adiponectin and heart failure (HF) and mortality, outcomes associated with PH, is unclear.

Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

Background: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown.

Methods: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.

Effects of Omecamtiv Mecarbil on Symptoms and Health-Related Quality of Life in Patients With Chronic Heart Failure: Results From the COSMIC-HF Study.

Background: Chronic heart failure with reduced ejection fraction impairs health-related quality of life (HRQL). Omecamtiv mecarbil (OM)-a novel activator of cardiac myosin-improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of OM on symptoms and HRQL in patients with chronic heart failure with reduced ejection fraction and elevated natriuretic peptides enrolled in the COSMIC-HF trial (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure).

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials.

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials.

Methods And Results: Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.

Gender Differences in Risk Factors Associated With Pulmonary Artery Systolic Pressure, Heart Failure, and Mortality in Blacks: Jackson Heart Study.

Background Pulmonary hypertension is prevalent in black individuals, especially women. Elevated pulmonary artery systolic pressure (PASP) is associated with significant morbidity and mortality. Methods and Results We developed linear and proportional hazards models to examine potential gender-related differences in risk factors for elevated PASP (estimated by transthoracic echocardiography) and PASP-associated clinical outcomes (incident heart failure admissions and mortality) in JHS (Jackson Heart Study) participants.