95 research outputs found
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: 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 (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€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 (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF 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 pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk 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
Investigations of low-frequency noise of GaN based heterostructure field-effect transistors
NRC publication: Ye
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function
Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 Ă 10?8) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function
Successful Thrombectomy Improves Functional Outcome in Tandem Occlusions with a Large Ischemic Core
International audienceBackground: Emergent stenting in tandem occlusions and mechanical thrombectomy (MT) of acute ischemic stroke related to large vessel occlusion (LVO-AIS) with a large core are tested independently. We aim to assess the impact of reperfusion with MT in patients with LVO-AIS with a large core and a tandem occlusion and to compare the safety of reperfusion between large core with tandem and nontandem occlusions in current practice. Methods: We analyzed data of all consecutive patients included in the prospective Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and March 2023 who presented with a pretreatment ASPECTS (Alberta Stroke Program Early CT Score) of 0â5 and angiographically proven tandem occlusion. The primary end point was a favorable outcome defined by a modified Rankin Scale (mRS) score of 0â3 at 90 days. Results: Among 262 included patients with a tandem occlusion and ASPECTS 0â5, 203 patients (77.5%) had a successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b-3). Reperfused patients had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR], 1.57 [1.22â2.03]; P < 0.001), higher rates of mRS score 0â3 (aOR, 7.03 [2.60â19.01]; P < 0.001) and mRS score 0â2 at 90 days (aOR, 3.85 [1.39â10.68]; P = 0.009) compared with nonreperfused. There was a trend between the occurrence of successful reperfusion and a decreased rate of symptomatic intracranial hemorrhage (aOR, 0.5 [0.22â1.13]; P = 0.096). Similar safety outcomes were observed after large core reperfusion in tandem and nontandem occlusions. Conclusions: Successful reperfusion was associated with a higher rate of favorable outcome in large core LVO-AIS with a tandem occlusion, with a safety profile similar to nontandem occlusion
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.)
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