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 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 functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Polimorfizmy genów układu renina-angiotensyna a ryzyko choroby wieńcowej serca

Background: Renin-angiotensin system genes are candidate genes in cardiovascular system diseases. Angiotensinconverting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) gene polymorphisms are considered risk factors in coronary heart disease (CHD).Aim: To evaluate the involvement of the ACE, AGT and AT1R genetic variants in predisposition to CHD as well as their association with other known risk factors.Methods: The study included 400 male subjects (200 with CHD and 200 healthy individuals). Genotypes were determined by a polymerase chain reaction (PCR). For the AGT and AT1R genes a restriction analysis of the PCR product was performed. The allele frequency and genotype distribution were compared between groups.Results: The allele and genotype frequencies of the ACE gene were similar in both groups, however, a significantly higher frequency of the DD genotype was observed in the presence of hyperlipidemia (39% vs 24% in non-hyperlipidemic subjects,

Coronary atherosclerosis in patients with acquired valvular disease

Background: Coronary atherosclerosis often coexists with acquired valvular disorders. There is growing evidence in literature that these two conditions may have common aetiology.Aim: To assess the incidence of coronary atherosclerosis in patients with acquired valvular disorders and to compare clinical parameters as well as the prevalence of risk factors between patients with aortic and mitral valve diseases.Methods: The study group consisted of 155 patients (101 males, 54 females, mean age 58.2±9.7 years) with acquired valvular disorder who between 2000 and 2002 underwent invasive cardiac evaluation in our department prior to planned cardiac surgery. Aortic stenosis was detected in 74 patients, aortic insufficiency - in 26, mitral stenosis - in 33, and mitral regurgitation - in 14 subjects. All patients underwent clinical evaluation, echocardiography, coronary angiography and laboratory tests.Results: Patients with aortic stenosis had similar prevalence of coronary atherosclerosis to patients with aortic insufficiency, and patients with mitral stenosis - to patients with mitral regurgitation. When the two groups - patients with aortic valve disease and patients with mitral valve disease were compared, significant coronary lesions were more often detected in patients with aortic valve disease (36% vs 12.8%,

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, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)