COMPARE LAAO: Rationale and design of the randomized controlled trial "COMPARing Effectiveness and safety of Left Atrial Appendage Occlusion to standard of care for atrial fibrillation patients at high stroke risk and ineligible to use oral anticoagulation therapy"

Contains fulltext : 252137.pdf (Publisher’s version ) (Open Access)BACKGROUND: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC randomized controlled trial (RCT) data is lacking. STUDY OBJECTIVES: To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications. STUDY DESIGN: This is a multicenter, investigator-initiated, open-label, blinded endpoint (PROBE), superiority-driven RCT. Patients with AF, a CHA₂DS₂-VASc score ≥2 for men and ≥3 for women and a long-term or permanent contraindication for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post-procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint-driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of 1 and a maximum of 5 years. Cost-effectiveness and budget impact analyses will be performed to allow decision-making on reimbursement of LAAO for the target population in the Netherlands. SUMMARY: The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use. NCT TRIAL NUMBER: NCT04676880

Sex differences in patients with out-of-hospital cardiac arrest without ST-segment elevation:A COACT trial substudy

Background: Whether sex is associated with outcomes of out-of-hospital cardiac arrest (OHCA) is unclear. Objectives: This study examined sex differences in survival in patients with OHCA without ST-segment elevation myocardial infarction (STEMI). Methods: Using data from the randomized controlled Coronary Angiography after Cardiac Arrest (COACT) trial, the primary point of interest was sex differences in OHCA-related one-year survival. Secondary points of interest included the benefit of immediate coronary angiography compared to delayed angiography until after neurologic recovery, angiographic and clinical outcomes. Results: In total, 522 patients (79.1% men) were included. Overall one-year survival was 59.6% in women and 63.4% in men (HR 1.18; 95% CI: 0.761.81;p = 0.47). No cardiovascular risk factors were found that modified survival. Women less often had significant coronary artery disease (CAD) (37.0% vs. 71.3%; p < 0.001), but when present, they had a worse prognosis than women without CAD (HR 3.06; 95% CI 1.31-7.19; p = 0.01). This was not the case for men (HR 1.05; 95% CI 0.67-1.65; p = 0.83). In both sexes, immediate coronary angiography did not improve one-year survival compared to delayed angiography (women, odds ratio (OR) 0.87; 95% CI 0.58-1.30;p = 0.49; vs. men, OR 0.97; 95% CI 0.45-2.09; p = 0.93). Conclusion: In OHCA patients without STEMI, we found no sex differences in overall one-year survival. Women less often had significant CAD, but when CAD was present they had worse survival than women without CAD. This was not the case for men. Both sexes did not benefit from a strategy of immediate coronary angiography as compared to delayed strategy with respect to one-year survival

Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation

Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care. (C) 2020 The Authors. Published by Elsevier Inc

Coronary Angiography After Cardiac Arrest Without ST Segment Elevation:One-Year Outcomes of the COACT Randomized Clinical Trial

Importance: Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking. Objective: To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy. Design, Setting, and Participants: A prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019. Interventions: Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery. Main Outcomes and Measures: Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year. Results: At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64). Conclusions and Relevance: In this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes

Clinical utility of remote platelet function measurement using P-selectin: assessment of aspirin, clopidogrel, and prasugrel and bleeding disorders

Vascular diseases such as myocardial infarction and ischemic stroke are associated with increased platelet function whilst the risk of recurrence is reduced by antiplatelet agents such as aspirin, clopidogrel, and prasugrel. However, some patients exhibit high platelet reactivity, especially with clopidogrel. Existing platelet function tests may not be ideal in that they can be expensive, are often time consuming, and measurements must be made near to the patient and within a few hours of blood collection. Platelet activation leads to translocation of P-selectin from alpha-granules to the cell surface. Following activation with arachidonic acid (which is blocked by aspirin) or adenosine diphosphate (inhibited by clopidogrel) and fixation, samples may be stored or posted to a laboratory performing flow cytometric quantification of platelet P-selectin expression. Acute myocardial infarction and ischemic stroke are associated with high platelet reactivity on clopidogrel in 6–58% of patients when assessed with P-selectin expression, and high reactivity was associated with an increased risk of recurrence after myocardial infarction. Use of P-selectin expression tests may also be of relevance to surgical and veterinary practice and the diagnosis of mild bleeding disorders. The present review explores this topic in further detail

Hemodialysis Removes Uremic Toxins That Alter the Biological Actions of Endothelial Cells

Chronic kidney disease is linked to systemic inflammation and to an increased risk of ischemic heart disease and atherosclerosis. Endothelial dysfunction associates with hypertension and vascular disease in the presence of chronic kidney disease but the mechanisms that regulate the activation of the endothelium at the early stages of the disease, before systemic inflammation is established remain obscure. In the present study we investigated the effect of serum derived from patients with chronic kidney disease either before or after hemodialysis on the activation of human endothelial cells in vitro, as an attempt to define the overall effect of uremic toxins at the early stages of endothelial dysfunction. Our results argue that uremic toxins alter the biological actions of endothelial cells and the remodelling of the extracellular matrix before signs of systemic inflammatory responses are observed. This study further elucidates the early events of endothelial dysfunction during toxic uremia conditions allowing more complete understanding of the molecular events as well as their sequence during progressive renal failure

Rationale for catheter-based therapies in acute pulmonary embolism

Pulmonary embolism (PE) is a common disease resulting in significant morbidity and mortality. High-risk features of PE are hypotension or shock, and early reperfusion is warranted to unload the strained right ventricle and improve clinical outcomes. Currently, systemic thrombolysis (ST) is the standard of care but is associated with bleeding complications. Catheter-based therapies (CDT) have emerged as a promising alternative having demonstrated to be equally effective while having a lower risk of bleeding. Several CDT are currently available, some combining mechanical properties with low-dose thrombolytics. Recent guidelines suggest that CDT may be considered in patients with high-risk PE who have high bleeding risk, after failed ST, or in patients with rapid haemodynamic deterioration as bail-out before ST can be effective, depending on local availability and expertise. In haemodynamically stable patients with right ventricular (RV) dysfunction (intermediate-risk PE), CDT may be considered if clinical deterioration occurs after starting anticoagulation and relative contraindications for ST due to bleeding risk exist. Decision on treatment modality should follow a risk-benefit analysis on a case by case base, weighing the risk of PE-related complications; i.e. haemodynamic deterioration vs. bleeding. As timely initiation of treatment is warranted to prevent early mortality, bleeding risk factors should be assessed at an early stage in all patients with acute PE and signs of RV dysfunction. To ensure optimal management of complex cases of PE and assess a potential CDT strategy, a multidisciplinary approach is recommended. A dedicated Pulmonary Embolism Response Team may optimize this process