Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation

Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.     

Restarting anticoagulation in prosthetic heart valve patients after intracranial haemorrhage: a 2-year follow-up

35 patients with oral anticoagulant (OAC) related intracranial or intraspinal haemorrhage were studied to determine treatment received, outcome and rate of recurrent bleeding and thromboembolism after restarting OAC. All patients underwent active anticoagulant reversal and in 14 patients with prosthetic heart valves (PHV) the INR remained below 2.0 for 0–19 d (median 7) with no thromboembolic events. 10 patients received heparin, although a therapeutic level was rarely achieved. 13 patients with PHV were restarted on OAC and followed for a median 23.5 months. One patient had recurrent intracranial bleeding. 3/13 patients had cerebral embolic events despite anticoagulation. We conclude that in PHV patients temporary cessation of OAC is safe and the risk of recurrent bleeding after restarting OAC is low.     

Concomitant Use of Direct Oral Anticoagulants with Antiplatelet Agents and the Risk of Major Bleeding in Patients with Nonvalvular Atrial Fibrillation

Purpose

Patients with nonvalvular atrial fibrillation commonly have comorbidities requiring concurrent use of oral anticoagulants and antiplatelets. There are no real-world data on the comparative safety of concomitant antithrombotic treatments in the era of direct oral anticoagulant (DOACs). Thus, we compared the incidence of intracranial hemorrhage, gastrointestinal bleeding, and other major bleeding between concomitant DOAC-antiplatelet use and concomitant vitamin K antagonist (VKA)-antiplatelet use in patients with nonvalvular atrial fibrillation.

Do anticoagulants improve survival in patients presenting with venous thromboembolism?

Anticoagulants have been available since around 1940 and have become the standard of treatment for venous thromboembolism (VTE) for over four decades. However, as with other treatments which became established before the evidence-based era, there is a paucity of evidence from randomized controlled trials validating their effectiveness in preventing the most feared complication of VTE, recurrent fatal pulmonary embolism (PE). Only two such trials have been performed, the results of which conflict. The bulk of data supporting their use are derived from three sources. First, studies of thromboprophylaxis, and comparisons of shorter and longer courses of anticoagulants in high-risk patients with established VTE have clearly demonstrated their effectiveness in primary and late secondary prevention. Given that heparin has an immediate onset of action, anticoagulants should therefore also be effective in early secondary prevention, the proposed mechanism of action in the acute treatment of VTE. Secondly, studies of inadequately treated patients have consistently shown higher recurrence rates than in those adequately treated. Finally, comparisons of outcomes in untreated and treated historical series, and of untreated historical series to treated series in the modern era have shown substantially lower rates of fatal PE in anticoagulated patients. Because these differences are so marked, harmonize with our current understanding of the mechanism of action of anticoagulants and are supported by other evidence, it is much more likely that they at least partly reflect the effectiveness of anticoagulants as opposed to being explicable purely in terms of accumulated biases and a changing distribution of disease severity.     

Low-molecular-weight heparin vs. unfractionated heparin in percutaneous coronary intervention: a combined analysis.

This meta-analysis assessed the rates of the efficacy and safety endpoints with intravenous low-molecular-weight heparin (LMWH) compared with unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI). Subcutaneous LMWH has compared favorably with UFH, but limited experience exists with intravenous LMWH for immediate anticoagulation in PCI. The meta-analysis included data from eight randomized trials in which patients received LMWH (n = 1,037) or UFH (n = 978) during PCI. Seven additional nonrandomized studies/registries were analyzed to assess the efficacy and safety of LMWH during PCI. Efficacy endpoints were ischemic events (usually a composite of death, myocardial infarction, and urgent revascularization) and the safety endpoint was bleeding (major, minor, or all bleeding). In the randomized studies, LMWH was comparable with UFH in terms of efficacy (6.2% vs. 7.5%) and major bleeding (0.9% vs. 1.8%). The analysis of pooled data, randomized or not, suggests potential improved efficacy (5.8% vs. 7.6%) and reduced major bleeding (0.6% vs. 1.8%) with LMWH (n = 3,787) compared with UFH (n = 978). During PCI, intravenous LMWH without coagulation monitoring has the potential to be at least as safe and efficacious as intravenous UFH. Further studies of LMWHs in PCI are therefore required.     

Perioperative venous thromboembolic disease and the emerging role of the novel oral anticoagulants: An analysis of the implications for perioperative management

Venous thromboembolism includes 2 inter-related conditions: Deep venous thrombosis and pulmonary embolism. Heparin and low-molecular-weight heparin followed by oral anticoagulation with vitamin K agonists is the first line and current accepted standard therapy with good efficacy. However, this therapeutic strategy has many limitations including the significant risk of bleeding and drug, food and disease interactions that require frequent monitoring. Dabigatran, rivaroxaban, apixaban, and edoxaban are the novel oral anticoagulants that are available for use in stroke prevention in atrial fibrillation and for the treatment and prevention of venous thromboembolism (HYPERLINK\l ”1). Recent prospective randomized trials comparing the NOACs with warfarin have shown similar efficacy between the treatment strategies but fewer bleeding episodes with the NOACs. This paper presents an evidence-based review describing the efficacy and safety of the new anticoagulants compared to warfarin.     

Anticoagulantes orales directos frente a antagonistas de la vitamina K en pacientes del «mundo real» con fibrilación auricular no valvular. Estudio FANTASIIA

Introduction and objectivesTo compare the long-term results of direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) in real-world-patients with nonvalvular atrial fibrillation (NVAF) in a nationwide, prospective study.MethodsThe FANTASIIA registry prospectively included outpatients with AF anticoagulated with DOAC or VKA (per protocol, proportion of VKA and DOAC 4:1), consecutively recruited from June 2013 to October 2014 in Spain. The incidence of major events was analyzed and compared according to the anticoagulant treatment received.ResultsA total of 2178 patients were included in the study (mean age 73.8 ± 9.4 years), and 43.8% were women. Of these, 533 (24.5%) received DOAC and 1645 (75.5%) VKA. After a median follow up of 32.4 months, patients receiving DOAC vs those receiving VKA had lower rates of stroke—0.40 (95%CI, 0.17-0.97) vs 1.07 (95%CI,0.79-1.46) patients/y, P = .032—, severe bleedings—2.13 (95%CI, 1.45-3.13) vs 3.28 (95%CI, 2.75-3.93) patients/y; P = .044—, cardiovascular death—1.20 (95%CI, 0.72-1.99) vs 2.45 (95%CI, 2.00-3.00) patients/y; P = .009—, and all-cause death—3.77 (95%CI, 2.83-5.01) vs 5.54 (95%CI, 4.83-6.34) patients/y; P = .016—. In a modified Cox regression model by the Andersen-Gill method for multiple events, hazard ratios for patients receiving DOAC were: 0.42 (0.16-1.07) for stroke; 0.47 (0.20-1.16) for total embolisms; 0.76 (0.50-1.15) for severe bleedings; 0.67 (0.39-1.18) for cardiovascular death; 0.86 (0.62-1.19) for all-cause death, and 0.82 (0.64-1.05) for the combined event consisting of stroke, embolism, severe bleeding, and all-cause death.ConclusionsCompared with VKA, DOAC is associated with a trend to a lower incidence of all major events, including death, in patients with NVAF in Spain.Full English text available from: www.revespcardiol.org/en     

The risks and characteristics of the delayed bleeding after endoscopic submucosal dissection for early gastric carcinoma in cases with anticoagulants

Abstract

Background

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric carcinoma. Vitamin K antagonists and direct oral anticoagulants (DOAC) were reported to increase the risk of delayed bleeding after ESD. However, the evaluation of ESD cases taking anticoagulants is scarce. We analyzed the risk and characteristics of delayed bleeding after gastric ESD in patients on anticoagulants.     

抗凝治疗量表中文版效度及信度分析

目的 抗凝治疗量表（anti clot treatment scale, ACTS）是评价患者抗凝治疗满意度的有效工具,该量表分为负担和获益两个维度。本文对中文版ACTS信度及效度进行评估。方法 通过多阶段抽样法,抽取服用抗凝药物4周以上心房颤动患者,调查其ACTS评分,采用结构效度、内部信度和重测信度分别对量表的信度和效度进行评价。结果 共计1 379例患者完成量表评价,通过主成分分析提取4个因子,共同因子累计总变异解释率为67.164%;内部信度分析抗凝负担维度（13条目）及抗凝获益维度（4条目）Cronbach's α系数分别为0.823及0.968;重测信度分析提示组间相关系数在负担和获益维度分别为0.783和0.674（P<0.01）。结论 中文版ACTS具有良好效度及信度,为抗凝治疗患者自测满意度提供良好评估工具。