Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients : An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban)

Members of the APEX Investigators working group are listed in Web of Science database publication.publishersversionPeer reviewe

Comparison of fatal or irreversible events with extended-duration betrixaban versus standard dose enoxaparin in acutely Ill medical patients : An APEX trial substudy

A complete list of the APEX Investigators is provided in Appendix S1 (attached PDF full text). Publisher Copyright: © 2017 The Authors.Background-Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. Methods and Results-This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). Conclusions-Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an ≈ 30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin.publishersversionPeer reviewe

Impact of thromboprophylaxis on hospital acquired thrombosis following discharge in patients admitted with COVID-19: multicentre observational study in the UK

Post-discharge thromboprophylaxis in patients admitted with COVID-19 remains controversial. We aimed to determine the impact of thromboprophylaxis on hospital acquired thrombosis (HAT) in patients (≥18 years) discharged following admission for COVID-19 in an observational study across 26 NHS Trusts in the UK (01.04.2020-31.12.2021). Overall, 8895 patients were included to the study: 971 patients were discharged with thromboprophylaxis and propensity score matched (PSM) with a desired ratio of 1:1, from patients discharged without thromboprophylaxis. Patients with heparin induced thrombocytopenia, major bleeding during admission and pregnant women were excluded. As expected from 1:1 PSM, no difference was observed in parameters between the two groups, including duration of hospital stay, except the thromboprophylaxis group had a significantly higher proportion who had received therapeutic dose anticoagulation during admission. There were no differences in the laboratory parameters especially D-dimers between the two groups at admission or discharge. Median duration of thromboprophylaxis following discharge from hospital was 4 weeks (1-8 weeks). No difference was found in HAT in patients discharged with TP versus no TP (1.3% vs. 0.92%, p = 0.52). Increasing age and smoking significantly increased the risk of HAT. Many patients in both cohorts had raised D-dimer at discharge but D-dimer was not associated with increased risk of HAT

Influenza and associated co-infections in critically ill immunosuppressed patients

BackgroundIt is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure.MethodsPreplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality.ResultsInfluenza infection status was categorized into four groups: patients with influenza alone (n=95, 5.8%), patients with influenza plus pulmonary co-infection (n=58, 3.6%), patients with non-influenza pulmonary infection (n=820, 50.9%), and patients without pulmonary infection (n=638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (PPeer reviewe

Platelet transfusions and thrombocytopenia in intensive care units : Protocol for an international inception cohort study (PLOT-ICU)

Introduction Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. Methods We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 x 10(9)/L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. Conclusion The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.Peer reviewe

Extended thromboprophylaxis with betrixaban in acutely ill medical patients

BACKGROUND: Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. METHODS: Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. RESULTS: A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). CONCLUSIONS: Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.)

Impact of an interatrial shunt device on survival and heart failure hospitalization in patients with preserved ejection fraction

Aims: Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short‐term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH). Methods and results: Heart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta‐analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post‐IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta‐analysis Global Group in Chronic Heart Failure score‐predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD‐treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan–Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload‐corrected exercise pulmonary capillary wedge pressure at the 6 months post‐IASD study were associated with HFH. Conclusions: The current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large‐scale ongoing randomized studies are required to confirm the potential benefit of this therapy

Qualitative study of experience of acceptance and commitment therapy (ACT+) amongst Survivors' Rehabilitation Evaluation after Cancer (SURECAN) trial participants and therapists: A protocol.

Background This interview study forms part of a mixed methods process evaluation of the Survivors’ Rehabilitation Evaluation after Cancer (SURECAN) trial to understand the experiences of participants (who are living with and beyond cancer) in receiving a form of acceptance and commitment therapy, and therapists providing the intervention. SURECAN is a multi-centre, pragmatic, individual participant randomised controlled trial of an intervention based on acceptance and commitment therapy supplemented by support for return to meaningful work and/or physical activity (ACT+). This qualitative study addresses the ways in which participants believe they benefit from ACT+ (or not), and how the ACT+ intervention might best be implemented into routine National Health Service (NHS) care. Methods The study investigates experiences of ACT+ by different participants to understand how we can optimise the ACT+ intervention and its delivery (assuming the intervention is successful). We will conduct individual interviews with participants who have taken part in the active arm of the SURECAN trial to understand their experiences of engaging with and receiving ACT+, their perceptions of the impact of the therapy, and relevant contextual factors influencing these experiences. In particular, we will focus on comparing our interview findings between those trial participants who improved and those who failed to improve (or worsened), in terms of quality of life following ACT+. Additionally, we will conduct individual interviews with therapists who have delivered ACT+ as part of the SURECAN trial, to understand their experiences of delivering ACT+. Conclusions Consistent with other qualitative protocols, this protocol is not registered. Instead, it is shared as a means of documenting ahead of time, how we are endeavouring to understand the ways in which a newly trialled talking therapy is received by patients and therapists, and how (if successful) it might be incorporated into the NHS

The Myocardial Ischemia Reduction with Acute Cholesterol Lowering trial: MIRACuLous or not, it's time to change current practice

The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study was the first trial to assess whether statins might be of clinical benefit in those with recently unstable coronary disease. MIRACL found that high-dose atorvastatin was safe and reduced the incidence of the composite endpoint, death, non-fatal myocardial infarction, resuscitated sudden cardiac death or emergent rehospitalization for recurrent ischemia at 16 weeks when compared with placebo. Despite a number of important study limitations, MIRACL's findings and the prior observation that inpatient initiation of lipid-lowering therapy is associated with higher rates of subsequent utilization, suggest that it is prudent to begin statin therapy when patients present with an acute coronary syndrome