scholarly journals Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study

2017 ◽  
Vol 117 (12) ◽  
pp. 2425-2434 ◽  
Author(s):  
Frederikus Klok ◽  
Walter Ageno ◽  
Stefano Barco ◽  
Harald Binder ◽  
Benjamin Brenner ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Phase Iii ◽  
Thrombin Inhibitor ◽  
Intermediate Risk ◽  
Safety Outcome ◽  
Efficacy Outcome ◽  
Heparin Anticoagulation

AbstractPatients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.

scholarly journals Outpatient Management in Patients with Venous Thromboembolism with Edoxaban: A Post Hoc Analysis of the Hokusai-VTE Study

2017 ◽  
Vol 117 (12) ◽  
pp. 2406-2414 ◽  
Author(s):  
Andria Medina ◽  
Gary Raskob ◽  
Walter Ageno ◽  
Alexander Cohen ◽  
Marjolein Brekelmans ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Similar Efficacy ◽  
Initial Therapy ◽  
Risk Difference ◽  
Efficacy And Safety ◽  
Open Label ◽  
Safety Outcome ◽  
Recurrent Vte

AbstractDirect oral anticoagulants (DOACs) facilitate the outpatient treatment of venous thromboembolism (VTE). However, the pivotal trials of DOACs have not reported outcomes separately for patients managed either as outpatients or in the hospital. We performed a subgroup analysis of the Hokusai-VTE study comparing efficacy and safety of edoxaban with warfarin in 8,292 patients with acute VTE. Patients received initial therapy with open-label enoxaparin or unfractionated heparin for ≥5 days in the hospital or as an outpatient at the discretion of the treating physician. Edoxaban or warfarin was then given for 3 to 12 months. The primary efficacy outcome was the cumulative incidence of symptomatic recurrent VTE at 12 months. The principal safety outcome was the incidence of clinically relevant bleeding (composite of major or clinically relevant non-major bleeding). Of the 5,223 consecutively enrolled patients with recorded hospital status and length of stay, 1,414 patients (27.1%) were managed as outpatients and 3,809 were managed in hospital. Among the outpatients, initial presentation was symptomatic deep-vein thrombosis (DVT) in 1,183 patients (83.7%) and pulmonary embolism (PE) in 231 patients (16.3%). Among the outpatients with DVT, recurrent VTE occurred in 18 (3.0%) given edoxaban and in 21 (3.6%) given warfarin (risk difference: −0.61, 95% confidence interval [CI]: −2.6 to 1.4). The principal safety outcome in outpatients occurred in 46 edoxaban patients (7.7%) and in 48 warfarin patients (8.3%; risk difference: −0.59, 95% CI: −3.7 to 2.5). Most outpatients had symptomatic DVT at presentation. In these patients, initial heparin followed by edoxaban had similar efficacy and safety to standard therapy with heparin and warfarin.

Evaluation of Efficacy and Safety of Direct Oral Anticoagulants (DOACS) in the Treatment of Venous Thromboembolism in Cancer Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5016-5016
Author(s):  
Ali McBride ◽  
Reem Diri ◽  
Chris Campen ◽  
Ivo Abraham
Keyword(s):  
Pancreatic Cancer ◽  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Secondary Prophylaxis ◽  
Efficacy And Safety ◽  
Bleeding Episodes ◽  
Current Guidelines

Abstract Background: Nearly twenty percent of all patients with deep venous thrombosis (DVT) or pulmonary embolism (PE) have an underlying malignancy. Current guidelines recommend low molecular weight heparin (LMWH)-based therapy for venous thromboembolism (VTE) treatment in cancer patients; however, patient considerations including access for treatment and monitoring, co-pay costs and self-administration can be a limitation for its use. Alternative treatments such as direct oral anticoagulants (DOACs) are an attractive alternative to patients and clinicians because of limited monitoring, fixed dosing and limited drug and food interaction. Current guidelines, including those of the American Society of Clinical Oncology and National Comprehensive Cancer Network, do not recommend the use of DOACs for VTE treatment at this time in cancer patients as there is limited data for VTE treatment and secondary prophylaxis with DOAC's. Methods :We performed a retrospective evaluation of cancer patients at our institution with an active VTE diagnosis who were administered DOACs (rivaroxaban, apixaban and dabigatran) between November 2013 and April 2016. Data collected included patient demographics, diagnosis, and chemotherapy regimen, previous history of VTE, and efficacy and safety during anticoagulation with DOAC's. Results : One hundred and thirty-seven patients were included in the study (Table 1), with 112 patients on rivaroxaban, 20 patients on apixaban, and 5 patients on dabigatran. DOACs were administered to treat deep venous thrombosis (DVT) in 86 patients, pulmonary embolism (PE) in 31 patients, and both DVT and PE diagnosis in 20 patients. Only four patients had a secondary clot on therapy during treatment: one patient with pancreatic cancer on apixaban developed recurrent portal vein thrombosis, and three patients with pancreatic cancer, adenocarcinoma of the lung, and Factor V Leiden deficiency on rivaroxaban; 2 patients developed recurrent DVT, and 1 patient developed recurrent PE. Overall, 34/137 (25%) patients experienced a total of 37 bleeding episodes, of which 33/37 were classified as clinically relevant non-major bleeding and 4/37 as minor bleeding. Thirty eight patients had their doses held ,discontinued, discontinued or switched to different anticoagulation therapy; in 11 patients secondary to bleeding, four failed therapy, three experienced intolerance to DOAC, two patients were changed secondary to drug interactions and two patients could not continue therapy secondary to co-pay costs, and two were held prior to surgery. Ten patients had recurrent (>2) bleeding episodes including epistaxis, hematochezia, hematuria, and hematemesis. Conclusion :In our analysis, DOACs did yield efficacy in cancer patients treated for secondary prophylaxis of VTE with few noted side effects. In our study, DOAC's did not cause fatal or major bleeding. Future prospective studies are warranted for secondary prophylaxis in this setting. Table 1. Baseline characteristics and outcomes of patients on DOAC's for Secondary DVT prophylaxis Evaluation of Efficacy and Safety of DOACsin the Treatment of Venous Thromboembolism in Cancer Patients Evaluation of Efficacy and Safety of DOACsin the Treatment of Venous Thromboembolism in Cancer Patients Disclosures McBride: Sanofi: Research Funding.

scholarly journals Treatment of Venous Thromboembolism in Special Populations with Direct Oral Anticoagulants

2020 ◽  
Vol 120 (06) ◽  
pp. 899-911
Author(s):  
Roisin Bavalia ◽  
Saskia Middeldorp ◽  
Gerhard Weisser ◽  
Christine Espinola-Klein
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Phase Iii Trials ◽  
Guidance Documents ◽  
Phase Iii Studies ◽  
Dose Reductions

AbstractAs a result of the successful completion of their respective phase III studies compared with vitamin K antagonists (VKAs), four direct oral anticoagulants (DOACs) have been approved for the treatment and secondary prevention of venous thromboembolism (VTE). These DOACs—apixaban, dabigatran, edoxaban, and rivaroxaban—have subsequently seen a steady uptake among clinicians since their approval. Despite the suitability of DOACs for a broad range of patients, they are not appropriate in certain situations, whereas in others they require additional considerations such as dose reductions. Subanalyses of phase III trials and studies on specific VTE patient populations have been conducted to evaluate the safety and efficacy of the DOACs in a broad range of settings, such as patients with renal impairment, patients with cancer, patients of childbearing potential, patients with multiple comorbidities and pediatric patients. Furthermore, many recent guidance documents from important hematological societies and other specialists have incorporated several of these developments. These documents also identify the patients for whom DOACs are not suitable and where traditional anticoagulation options such as heparins or VKAs should be considered instead. This review provides an overview of key VTE patient subgroups, the clinical evidence supporting the use of anticoagulation in these patients, and a discussion of the most appropriate approaches to their management, including considerations such as dosing, acute and extended treatment durations, and DOAC selection.

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Left Ventricular Thrombus

2020 ◽  
pp. 106002802097511 ◽  
Author(s):  
Andrew Willeford ◽  
Wenhong Zhu ◽  
Craig Stevens ◽  
Isac C. Thomas
Keyword(s):  
Primary Outcome ◽  
Randomized Clinical Trials ◽  
Medical Center ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Left Ventricular ◽  
Systemic Embolism ◽  
Safety Outcome ◽  
Efficacy Outcome ◽  
Unadjusted Analysis

Background Use of direct oral anticoagulants (DOACs) for the treatment of left ventricular (LV) thrombus has gained considerable interest. Objective We aimed to evaluate if DOACs are effective in the treatment of LV thrombus compared with warfarin. Methods We evaluated the medical records of patients diagnosed with a new LV thrombus at a tertiary medical center. The primary outcome was the composite of thrombus persistence, stroke, or systemic embolism. We adjusted for potential confounders using multiple logistic regression. The safety outcome was the composite of hemorrhagic stroke or bleeding requiring blood transfusion. Results A total of 129 patients were treated with warfarin and 22, with a DOAC. In unadjusted analysis, 54.3% of patients treated with warfarin met criteria for the efficacy outcome as compared with 40.9% of patients treated with a DOAC ( P = 0.25). In adjusted analysis, no difference between groups was observed (odds ratio = 0.39; 95% CI = 0.14-1.06; P = 0.07 for DOAC vs warfarin). In all, 3.9% of patients treated with warfarin met safety criteria as compared with 4.5% of patients treated with a DOAC. A total of 8 patients in the warfarin group had a stroke or systemic embolism as compared with 0 patients in the DOAC group ( P = 0.37). Conclusion and Relevance Our data suggest that DOACs may be reasonable alternatives for treatment of LV thrombus. When added to the totality of available studies, this study demonstrates that the effectiveness of DOACs in LV thrombus remains uncertain. Randomized clinical trials are needed.

scholarly journals Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review

2014 ◽  
pp. 627 ◽  
Author(s):  
Antonio Gomez-Outes ◽  
M. Luisa Suarez-Gea ◽  
Ramon Lecumberri ◽  
Ana-Isabel Terleira-Fernandez ◽  
Emilio Vargas-Castrillon
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Evidence Based

Benefit–risk profile of non-vitamin K antagonist oral anticoagulants in the management of venous thromboembolism

2015 ◽  
Vol 113 (02) ◽  
pp. 231-246 ◽  
Author(s):  
Walter Ageno ◽  
Jan Beyer-Westendorf
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Risk Groups ◽  
Phase Iii ◽  
Thrombin Inhibitor ◽  
Wound Complications ◽  
Orthopaedic Patients ◽  
Prevention And Treatment

SummaryThe prevention and treatment of venous thromboembolism (VTE) remains a clinical challenge, primarily owing to drawbacks associated with the use of heparins and vitamin K antagonists (VKAs). These and other factors, including a growing elderly population, mean that VTE presents a continuing burden to patients and physicians. Anticoagulant therapy is a fundamental approach for VTE management. Non- VKA oral anticoagulants, including the factor Xa inhibitors apixaban, edoxaban and rivaroxaban, and the thrombin inhibitor dabigatran, have been studied in phase III trials across a spectrum of thromboembolic disorders. These agents offer simplified care, with similar or improved efficacy and safety outcomes compared with heparins and vitamin K antagonists. There are several factors a physician must consider when prescribing an anticoagulant. An important consideration with all anticoagulant use is bleeding risk, especially in high-risk groups such as the elderly or those with renal impairment or cancer. In orthopaedic patients, other risks include a need for surgical revision or blood transfusion, or wound complications. Therefore, the clinical benefits of an anticoagulant should ideally be balanced with any risks associated with the therapy. Quantitative benefit–risk assessments are lacking, and owing to differences in trial design the non-VKA oral anticoagulants cannot be compared directly. Based on trial and “reallife” data, this review will summarise the clinical data for the non-VKA oral anticoagulants in the prevention and treatment of VTE, focusing on the balance between the benefits and risks of anticoagulation with these drugs, and their potential impact on VTE management.

scholarly journals The current place of direct oral anticoagulants in the prevention/treatment of venous thromboembolism

2020 ◽  
Vol 70 (5) ◽  
pp. 284-296
Author(s):  
Maja Tomić
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Secondary Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Comparable Efficacy ◽  
Thrombin Inhibitor ◽  
Medical Patients ◽  
Vte Prophylaxis

Venous thromboembolism (VTE; includes deep venous thrombosis, DVT, and pulmonary embolism, PE) represents the third most common acute cardiovascular syndrome. Contemporary VTE management comprises primary prevention in high-risk patients, treatment of established VTE, and prevention of its recurrence (secondary prevention). Anticoagulants are the basis of VTE pharmacological prophylaxis and treatment. For several decades, parenteral (heparin and low-molecular-weight heparins, LMWHs) and oral anticoagulants (vitamin K antagonists, VKAs) have been the cornerstone of VTE prevention/treatment. The introduction of direct oral anticoagulants (DOACs: thrombin inhibitor dabigatran and Xa inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban) markedly improved the management of VTE by overcoming many disadvantages of conventional anticoagulants. For primary VTE prevention in patients after total hip/knee arthroplasty, rivaroxaban, apixaban, and dabigatran are preferred over LMWHs, due to comparable efficacy and safety, but favourable acceptability (avoided everyday injections). In other high-risk populations (other surgical patients, acutely ill medical patients), LMWHs are still the recommended option. Betrixaban is currently the only DOAC approved for VTE prophylaxis in medically ill patients during and after hospitalization. For acute VTE treatment and secondary prevention, DOACs (rivaroxaban, apixaban, edoxaban, and dabigatran) are recommended as the first-line therapy in the general population. DOACs proved to be similarly effective but safer than VKAs. In some specific populations, DOACs also seem to be advantageous over conventional treatment (patients with renal impairment, elderly, long-term secondary prevention in cancer patients). Currently, there is no data from randomized head-to-head comparative studies between the DOAC classes or representatives so the choice is made mainly according to patient characteristics and pharmacokinetic properties of the drug.

scholarly journals Effectiveness and Safety of Apixaban for Treatment of Venous Thromboembolism in Daily Practice

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e119-e126 ◽  
Author(s):  
Stephan V. Hendriks ◽  
Frederikus A. Klok ◽  
Wilhelmina J.E. Stenger ◽  
Albert T.A. Mairuhu ◽  
Jeroen Eikenboom ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Daily Practice ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Phase 3 ◽  
Recurrent Vte

Abstract Introduction Phase 3 trials have shown comparable efficacy of direct oral anticoagulants (DOACs) and vitamin K antagonists in patients with acute venous thromboembolism (VTE), with less major bleeding events in patients randomized to DOAC treatment. With DOACs being increasingly used in clinical practice, evaluation of the DOACs in daily practice-based conditions is needed to confirm their safety and effectiveness. The aim of this study is to evaluate the effectiveness and safety of apixaban in VTE patients in daily practice. Methods In this retrospective cohort study, consecutive patients diagnosed with VTE in two Dutch hospitals (Leiden University Medical Center, Leiden and Haga Teaching Hospital, The Hague) were identified based on administrative codes. We assessed recurrent VTE, major bleeding and mortality during a 3-month follow-up period in those treated with apixaban. Results Of 671 consecutive VTE patients treated with apixaban, 371 presented with acute pulmonary embolism (PE) and 300 patients with deep-vein thrombosis. During 3 months treatment, 2 patients had a recurrent VTE (0.3%; 95% confidence interval [CI]: 0.08–1.1), 12 patients had major bleeding (1.8%; 95% CI: 1.0–3.2), and 11 patients died (1.6%; 95% CI: 0.9–2.9), of which one patient with recurrent PE and one because of a intracerebral bleeding. Conclusion In this daily practice-based cohort, apixaban yielded a low incidence of recurrent VTE, comparable to the phase 3 AMPLIFY study patients. The incidence of major bleeding was higher than in the AMPLIFY-study patients, reflecting the importance of daily practice evaluation and the fact that results from phase III clinical studies cannot be directly extrapolated toward daily practice.

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

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