Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: Rationale and design of the HoT-PE Trial

SummaryPulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute lowrisk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligib…

Efficacy and Safety of Tinzaparin in CAT Patients with Metastatic Disease

Introduction Venous thromboembolism (VTE) frequently complicates the course of active cancer with a significant impact on morbidity and mortality. The results of CATCH trial for treatment of cancer-associated thrombosis (CAT) have been reported and included patients with and without metastatic disease. As metastatic disease is known to be associated with a higher risk of recurrent VTE and bleeding, we performed these post hoc analyses to assess the recurrent VTE (rVTE), recurrent deep vein thrombosis (rDVT), and bleeding events (major bleeding (MB), clinically relevant (CRB) and clinically relevant non-major (CRNMB)) in patients with CAT with metastatic disease. Risk factors associated with…

The Role for Combined Antithrombotic Therapy with Platelet and Coagulation Inhibition After Lower Extremity Revascularization

Evidence for antithrombotic treatment following lower extremity revascularization (LER) for peripheral artery disease (PAD) is limited, leading to weak and conflicting guideline recommendations and heterogeneous practice patterns. This variability in post-LER antithrombotic treatment raises quality-of-care issues that have long been under-studied. This Viewpoint reviews the most updated guidelines, currently-available evidence, and contemporary data about practice patterns and practitioner opinions in this area. Particular attention is paid to distinctions between antiplatelet therapy, anticoagulant therapy, and combination therapy in light of the recent VOYAGER-PAD (Vascular Outcomes Study…

Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials.

Abstract Aims Peripheral artery disease (PAD) patients suffer a high risk of major cardiovascular (CV) events, with athero-thrombo-embolism as the underlying pathophysiologic mechanism. Recently, two large randomized clinical trials evaluated the efficacy and safety of low-dose rivaroxaban twice daily plus aspirin in stable PAD outpatients and those immediately after peripheral revascularization. We sought to determine if the effects of low-dose rivaroxaban and aspirin compared to aspirin alone are consistent across this broad spectrum of PAD patients. Methods and results We conducted a random-effects meta-analysis of the COMPASS and VOYAGER randomized trials among 11 560 PAD patients (4996…

Reduction in Acute Limb Ischemia With Rivaroxaban Versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD

Background: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. Methods: The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxa…

Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.

Background: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. Methods: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed …

Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial

Summary Background Superficial-vein thrombosis can lead to deep-vein thrombosis and pulmonary embolism. Rivaroxaban, an oral factor Xa inhibitor, might simplify treatment compared with fondaparinux because it does not require daily subcutaneous injection and is cheaper. We compared efficacy outcomes in patients with superficial-vein thrombosis and additional risk factors given either rivaroxaban or fondaparinux to assess whether rivaroxaban is non-inferior to fondaparinux in the prevention of thromboembolic complications. Methods In this open-label, masked endpoint, randomised, non-inferiority phase 3b trial, we recruited patients aged 18 years or older with symptomatic superficial-vein thr…

Total Ischemic Event Reduction With Rivaroxaban After Peripheral Arterial Revascularization in the VOYAGER PAD Trial

Patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) are at high risk of major adverse limb and cardiovascular events. The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial demonstrated that rivaroxaban 2.5 mg twice daily reduced first events by 15%. The benefit of rivaroxaban on total (first and subsequent) events in this population is unknown.This study sought to evaluate the total burden of vascular events in patients with PAD after LER and the efficacy o…

Cancer‐associated venous thromboembolism: Treatment and prevention with rivaroxaban

Abstract Cancer‐associated venous thromboembolism (VTE) is a frequent, potentially life‐threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer‐associated thrombosis (CAT); factor Xa–inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), which have long been recommended for the treatment of VTE in patients without cancer, have been investigated in this setting. The first randomized comparisons of DOACs against low‐molecular‐weight heparin for the treatment of CAT indicated that DOACs are efficacious in this setting, with findings reflected in recent updates to published guidan…

Evaluation of direct oral anticoagulants in superficial-vein thrombosis – Authors' reply

Direct oral anticoagulants for the treatment of pulmonary embolism in patients with renal impairment.

Pulmonary embolism (PE) is associated with adverse outcomes and substantial morbidity and mortality. Patients with PE often have renal impairment because of shared risk factors and close links between the renal and cardiovascular systems. Furthermore, patients with PE and renal impairment are at increased risk of recurrent thrombosis. Therefore, anticoagulation is crucial to treat the acute event, prevent recurrent venous thromboembolism (VTE), and optimize patient outcomes. However, when treated with an anticoagulant, patients with renal impairment also have an elevated risk of bleeding. Direct oral anticoagulants (DOACs) are the first-choice treatment for acute VTE in eligible patients. H…

Rationale and design for the Vascular Outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD).

Abstract Background Patients with peripheral artery disease (PAD) undergoing a lower-extremity revascularization are at heightened risk for ischemic cardiac and limb events. Although intensification of antithrombotic therapy after revascularization has demonstrated benefit in coronary disease populations, this approach has not been well studied or shown consistent benefit in PAD. Recent trial evidence demonstrated that a treatment strategy of rivaroxaban added to background antiplatelet therapy reduced ischemic risk in patients following recent acute coronary syndromes, as well as in patients with stable atherosclerotic vascular disease. Whether these benefits extend to the population of pa…

Low-dose rivaroxaban plus aspirin in older patients with peripheral artery disease undergoing acute limb revascularization: insights from the VOYAGER PAD trial

Abstract Aims In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk–benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described. Methods and results The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarct…

The role of heparin lead-in in the real-world management of acute venous thromboembolism: The PREFER in VTE registry

Abstract Introduction The appropriate strategy for initiating oral anticoagulant (OAC) therapy after an acute venous thromboembolism (VTE) depends on the intermediate-term anticoagulant to be used. While heparin bridging to vitamin K antagonists (VKA) is required, the direct oral anticoagulants (DOAC) rivaroxaban (30 mg/day) and apixaban (10 mg/day) can be initiated directly without parenteral anticoagulation. The objective was to evaluate OAC initiation patterns in clinical practice. Materials and methods PREFER in VTE was an international, non-interventional registry conducted between January 2013 and August 2015. Consecutive acute VTE patients were grouped based on their OAC treatment at…

Editor's Choice – European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis

European Society for Vascular Surgery (ESVS) 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis

Efficacy and Safety of Tinzaparin in CAT Patients with Hematological Malignancy

Abstract Introduction In patients with hematological cancers, the high risk of bleeding raises serious concerns when anticoagulant therapy is initiated for treatment of acute venous thromboembolism (VTE). In the CATCH trial, we showed that tinzaparin is associated with a significantly lower risk of clinically relevant bleeding (CRB) and clinically relevant non-major bleeding (CRNMB) compared with warfarin therapy in patients with a solid tumor or hematological cancer. Hence, we performed a post-hoc analysis to assess the risk of recurrent VTE (rVTE) and bleeding in the hematological cancer patient subgroup. Risk factors associated with rVTE and bleeding were also explored. Methods CATCH (Cl…

Treatment of pulmonary embolism.

International audience; The treatment of pulmonary embolism is going to be deeply modified by the development of Direct Oral Anticoagulants (DOACs). There are currently three anti-Xa factors (rivaroxaban, apixaban, edoxaban) and one anti-IIa factor (dabigatran) labeled by the FDA and the EMA. All these drugs are direct anticoagulant, orally effective, without the need for adaptation to hemostasis test. As kidney excretion is involved for all of them, they are contra-indicated in patients with severe renal failure (creatinine clearance<30mL/min according to Cockcroft & Gault formula). All the anti-Xa factor drugs are metabolized by liver cytochromes and then contra-indicated in case of liver…

Women, thrombosis, and cancer: A gender-specific analysis.

Venous thromboembolism (VTE) is a major common complication in cancer patients. Risk-adapted thromboprophylaxis and antithrombotic therapy for patients diagnosed with VTE can reduce the recurrence of VTE events. Thrombotic risk varies according to cancer type, stage, and comorbidities. The current review analyzes most recent data and provides clinical guidance for the management of women with cancer-associated thrombosis.

Fundamental Research in Oncology and Thrombosis 2 (FRONTLINE 2): A Follow‐Up Survey

Abstract Background Fundamental Research in Oncology and Thrombosis (FRONTLINE) is a global survey of physicians' perceptions and practice in the management of venous thromboembolism (VTE) in patients with cancer. Materials and Methods The present survey, FRONTLINE 2, follows the original FRONTLINE survey (published in The Oncologist in 2003) and provides insights into how physicians perceive risk of VTE in cancer and approach its prophylaxis and treatment. Results Between November 2015 and February 2016, 5,233 respondents participated, representing cancer physicians and surgeons. Most believed that less than one in five patients with any cancer might be at risk of VTE, with a slightly high…

Survival and quality of life after early discharge in low-risk pulmonary embolism.

IntroductionEarly discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes.MethodsThe multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, …

Management and Outcomes of Patients with Isolated Superficial Vein Thrombosis under Real Life Conditions (INSIGHTS-SVT).

Objective Management and outcomes of superficial vein thrombosis (SVT) are highly variable and not well described. Therefore, the INvestigating SIGnificant Health TrendS in the management of SVT (INSIGHTS-SVT) study collected prospective data under real life conditions. Methods Prospective observational study of objectively confirmed acute isolated SVT. The primary outcome was a composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and extension or recurrence of SVT at three months. The primary safety outcome was clinically relevant bleeding. Results A total of 1 150 patients were included (mean age 60.2 ± 14.7 years; 64.9% women; mean BMI 29.4 ± 6.3 kg/m2). SVT was …

Antithrombotic therapies in aortic and peripheral arterial diseases in 2021: a consensus document from the ESC working group on aorta and peripheral vascular diseases, the ESC working group on thrombosis, and the ESC working group on cardiovascular pharmacotherapy

AbstractThe aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to be incorporated into clinical practice. In the absence of specific indications for chronic oral anticoagulation due to concomitant cardiovascular disease, a single antiplatelet agent is the ba…

Pulmonary embolism in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

Objectives\ud Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from patients in Europe is scarce. The aim of this study was to report the impacts of PE on healthcare resource utilization (HCRU) and return to work using the PREFER in VTE registry.\ud \ud Methods\ud The PREFER in VTE registry was a prospective, observational, multicenter study in seven European countries, aiming to provide data concerning treatment patterns, HCRU, mortality, quality of life and work-loss. Patients with a first-time or recurrent PE were included and followed up at 1, 3, 6 and 12 months. Treatment patterns, re-hospitalization rates, length of hospital stays (LOS), and a…

Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH)

Venous thromboembolism (VTE) is a major cause of maternal morbidity during pregnancy and the postpartum period. However, because there is a lack of adequate study data, management strategies for pregnancy-associated VTE must be deduced from observational stu-dies and extrapolated from recommendations for non-pregnant patients. In this review, the members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH) have summarised the evidence that is currently available in the literature to provide a practical approach for treating pregnancy-associated VTE. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low molecular weight heparin …

2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism

ACS : acute coronary syndrome AMPLIFY : Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-line Therapy aPTT : activated partial thromboplastin time b.i.d. : bis in diem (twice daily) b.p.m. : beats per minute BNP : brain natriuretic peptide BP : blood pressure CI : confidence interval CO : cardiac output COPD : chronic obstructive pulmonary disease CPG : Committee for Practice Guidelines CRNM : clinically relevant non-major CT : computed tomographic/tomogram CTEPH : chronic thromboembolic pulmonary hypertension CUS : compression venous ultrasonography DSA : digital subtraction angiography DVT : deep vein thrombosis ELISA : enzyme-linked immunosorben…

Management of Patients with Asymptomatic and Symptomatic Carotid Artery Disease: Update on Anti-Thrombotic Therapy

AbstractThe most common causes of ischaemic stroke are represented by carotid artery atherosclerotic disease (CAAD) and atrial fibrillation. While oral anticoagulants substantially reduce the incidence of thromboembolic stroke (&lt; 1%/year), the rate of ischaemic stroke and other cardiovascular disease events in patients with CAAD remains high, ranging from 8.4 to 18.1 events per 100 patient-years. Similar to any other atherosclerotic disease, anti-thrombotic therapies are proposed for CAAD to reduce stroke and other cardiovascular events. The 2017 European Society of Cardiology (ESC)/European Society for Vascular Surgery (ESVS) guidelines recommend for patients with asymptomatic CAAD ≥60%…

Safety and Effectiveness of Paclitaxel Drug-Coated Devices in Peripheral Artery Revascularization

Abstract Background Paclitaxel drug-coated devices (DCDs) were developed to improve lower extremity revascularization (LER) patency in peripheral artery disease (PAD) but have been associated with long-term mortality. Objectives This study assessed DCD safety and effectiveness in LER for PAD. Methods VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) randomized patients with PAD who underwent LER to rivaroxaban or placebo. The primary VOYAGER PAD study efficacy and safety outcomes were composite cardiovascular and limb events and Thrombolysis In Myocardial Infarction major bleeding. For prespe…

Verlängerte Sekundärprophylaxe nach venöser Thromboembolie

Was ist neu? Aktuelle Studien Kurz nach Absetzen der oralen Antikoagulation kommt es zu einem etwa 2- bis 3-fachen Anstieg von VTE-Rezidiven. Das Rezidivrisiko ist besonders hoch nach einer VTE, die ohne identifizierbaren Auslöser aufgetreten war oder wenn nur weiche, unsichere auslösende Risikofaktoren vorlagen, sowie bei fortbestehenden Risikofaktoren, wie z. B. einer Krebserkrankung. Konsensusdokument über auslösende Risikofaktoren für venöse Thromboembolie In einem aktuellen Konsensusdokument wurden die zugrundeliegenden Risikofaktoren definiert und in 3 Gruppen klassifiziert. Direkte orale Antikoagulanzien Eine reduzierte Dosis von DOAK ermöglicht eine wirksame verlängerte Sekundärprop…

Rivaroxaban in Peripheral Artery Disease after Revascularization

Abstract Background Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and ...