Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

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

Multi Ray Model for Near-Ground Millimeter Wave Radar

A quasi-optical multi-ray model for a short-range millimeter wave radar is presented. The model considers multi-path effects emerging while multiple rays are scattered from the target and reflected to the radar receiver. Among the examined scenarios, the special case of grazing ground reflections is analyzed. Such a case becomes relevant when short range anti-collision radars are employed in vehicles. Such radars operate at millimeter wavelengths, and are aimed at the detection of targets located several tens of meters from the transmitter. Reflections from the road are expected to play a role in the received signal strength, together with the direct line-of-sight beams illuminated and scattered from the target. The model is demonstrated experimentally using radar operating in the W-band. Controlled measurements were done to distinguish between several scattering target features. The experimental setup was designed to imitate vehicle near-ground millimeter wave radars operating in vehicles. A comparison between analytical calculations and experimental results is made and discussed

Quasi Optical Multi-Ray Model For Wireless Communication Link in Millimeter Wavelengths

The spectrum of millimeter waves lay above 30GHz. The band between 30GHz up to 300GHz is called Extremely High Frequencies (EHF). This wide spectrum is relatively free of users and have recently became relevant for realizations of wireless communications an radars, including the fifth generation (5G) of cellular communications. Due to the short wavelengths, the propagation of millimeter waves can be analyzed using quasi-optical ray techniques. We present a multi-ray analysis of millimeter wave wireless link in the presence of multipath. The analysis is applicable for indoor and outdoor links and considers reflections from walls and buildings. It is shown that line-of-sight is not necessarily required in scenarios where multiple reflections exist as in long corridors, canyons and tunnels. The theoretical results are verified experimentally with a link in the W-band (94GHz)

Quasi Optical Multi-Ray Model For Wireless Communication Link in Millimeter Wavelengths

The spectrum of millimeter waves lay above 30GHz. The band between 30GHz up to 300GHz is called Extremely High Frequencies (EHF). This wide spectrum is relatively free of users and have recently became relevant for realizations of wireless communications an radars, including the fifth generation (5G) of cellular communications. Due to the short wavelengths, the propagation of millimeter waves can be analyzed using quasi-optical ray techniques. We present a multi-ray analysis of millimeter wave wireless link in the presence of multipath. The analysis is applicable for indoor and outdoor links and considers reflections from walls and buildings. It is shown that line-of-sight is not necessarily required in scenarios where multiple reflections exist as in long corridors, canyons and tunnels. The theoretical results are verified experimentally with a link in the W-band (94GHz)