Role Of Novel Oral Anticoagulants Research Articles

Novel oral anticoagulant in treatment of left ventricular thrombus in acute coronary syndrome – A case series

Introduction: Left ventricular (LV) thrombus is a known complication of myocardial infarction (MI) and it usually occurs in areas of poorly contracting LV muscle as a result of endocardial injury with associated inflammation. There is a high risk of embolization within 3 months among patients with MI complicated by mural thrombus and this risk is maximum during the first 1–2 weeks. We report a case series of five patients who presented with acute coronary syndrome with LV apical thrombus and treated with triple anti-thrombotic therapy of rivaroxaban, aspirin, and clopidogrel. Case Series: Our series involves 5 cases who developed LV apical thrombus after acute coronary syndrome. Four patients had anterior wall ST-elevation MI (STEMI) whereas 1 patient had inferior wall STEMI. One of the patients with anterior STEMI also had COVID pneumonitis. All of these patients received triple anti-thrombotic therapy consisting of tab Aspirin 75 mg OD, tab clopidogrel 75 mg OD, and tab rivaroxaban 20 mg OD for 3 months duration. Repeat ECHO after 3 months showed complete resolution of LV thrombus in all of our cases. Discussion: LV thrombus reported in STEMI patients is from 1.6% up to 39% in various studies. The incidence of LV thrombus is on decreasing trend as a result of modern revascularization strategies. The role of novel oral anticoagulants (NOACs) in treating LV thrombus is scant as compared to oral Vitamin K antagonists (VKAs) like warfarin. The current recommendation for anticoagulation in the presence of a LV thrombus after acute coronary syndrome is with VKAs for up to 6 months. Conclusion: Although there is uncertainty in decision-making regarding antithrombotic therapy, our case series demonstrate that triple antithrombotic therapy with NOACs results in resolution of LV thrombus without any additional bleeding events in patients presenting with acute coronary syndrome. NOACs have an advantage of not requiring PT/INR monitoring and have less bleeding complications. Further large-scale research or randomized controlled trials are needed to find the optimal therapies in such cases.

Recommendations of the Spanish Rheumatology Society for primary antiphospholipid syndrome. Part II: Obstetric antiphospholipid syndrome and special situations

ObjectiveThe difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS. MethodsA panel of 4 rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for the document elaboration, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network, SIGN levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques). ResultsForty-six recommendations were drawn up, addressing 5 main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the last 25, referring to the areas of: obstetric APS and special situations. The document provides a table of recommendations and treatment algorithms. ConclusionsUpdate of SER recommendations on APS is presented. This document corresponds to part II, related to obstetric SAF and special situations. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A Part I has also been prepared, which addresses aspects related to diagnosis, evaluation and treatment.

Recommendations of the Spanish Rheumatology Society for primary antiphospholipid syndrome. Part I: Diagnosis, evaluation and treatment

ObjectiveThe difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for primary antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS. MethodsA panel of four rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for drafting the document, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network [SIGN] levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques). Results46 recommendations were drawn up, addressing five main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the first 21, referring to the areas of: diagnosis, evaluation and treatment of primary APS. The document provides a table of recommendations and treatment algorithms. ConclusionsAn update of the SER recommendations on APS is presented. This document corresponds to part I, related to diagnosis, evaluation and treatment. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A part II has also been prepared, which addresses aspects related to obstetric SAF and special situations.

Intake of NOAC is associated with hematoma expansion of intracerebral hematomas after traumatic brain injury.

Novel oral anticoagulants are increasingly replacing vitamin K antagonists in the prophylaxis of thromboembolism as they are associated with lower incidence of spontaneous intracerebral hematomas and they do not require drug level monitoring. However, management dilemmas are apparent in patients on novel oral anticoagulants who have developed intracerebral hematomas after traumatic brain injury, since clinical experience with their reversal strategies is limited. We retrospectively studied 90 patients with traumatic intracerebral hematomas undergoing treatment at the surgical intensive care unit of the BG University Clinic Bergmannsheil in Bochum between 2015 and 2018. We analyzed potential prognostic factors for their radiological (expansion of intracerebral hematoma) and clinical (patients' outcome) course, in particular the role of novel oral anticoagulants. 71.1% of patients were male; mean age was 67.3years. Hematoma's expansion occurred in 35.9% of our patients, whereas 62.2% of our cohort showed a favorable outcome, defined as Glasgow Outcome Scale 4 and 5. Intake of novel oral anticoagulants was associated with a higher rate of hematoma's expansion compared to patients on vitamin K antagonists (p = 0.05) or to patients with normal coagulation status (p = 0.002). A younger age (p < 0.001) was identified as the sole independent prognostic factor for a more favorable outcome, after excluding our cases, who underwent a cardiopulmonary resuscitation. Our data showed a higher rate of hematoma's expansion in patients with traumatic intracerebral hematomas on novel oral anticoagulants vs. vitamin K antagonists and recommend the consideration of prophylactic reversal of the novel oral anticoagulants at admission. Larger prospective trials are warranted to conclude whether the current specific reversal protocols are safe and effective.

ANMCO/GISE/SICCH Inter-Society Consensus Document: Antithrombotic therapy after surgery or structural interventional procedures for valvular heart diseases: how to treat postoperative complications

Continuous improvement of technologies, devices and drugs needs a renewal and update of current recommendations and guidelines on antithrombotic strategies, especially in those fields where literature lacks of established scientific evidences. Accordingly, the aim of this consensus statement is to provide support for antithrombotic therapy based on current guidelines and the most recent scientific evidences.After an overview on the currently available devices, the appropriate therapy according to type of procedure and implanted device is discussed. The occurrence of postoperative thromboembolic and/or hemorrhagic complications is analyzed, along with the appropriate diagnostic tools and therapeutic approach. A section is dedicated to counseling to pregnancy in women with heart valve prosthesis. Finally, the role of novel oral anticoagulants is discussed, and indications are provided for the management of patients undergoing surgery or interventional procedures on oral anticoagulation therapy.

The Role of Novel Oral Anticoagulants and Antiplatelet Therapy after Percutaneous Coronary Intervention: Individualizing Therapy to Optimize Outcomes.

The number of patients undergoing percutaneous coronary intervention (PCI) who mandate additional oral anticoagulant therapy has been increasing. Dual antiplatelet therapy (DAPT) is associated with reduced ischemic events including stent thrombosis, myocardial infarction and stroke following PCI. However, the tradeoff is an increased risk for bleeding while on DAPT. The addition of a novel oral anticoagulant (NOAC) further increases the likelihood of bleeding while on antiplatelet therapy. Thus, the overall risks and benefits for each patient undergoing PCI on NOAC must be assessed and therapy individualized to ensure optimal therapy for each unique situation. Patients on NOAC undergoing PCI should undergo routine assessment with intravascular imaging as the role of high-risk lesion-related features have increased importance prior to determining optimal duration of treatment with DAPT. We review the best practices for the pharmacologic management of patients requiring anticoagulation with NOAC who are treated with PCI and require antiplatelet therapy.

Novel oral anticoagulants in chronic kidney disease: ready for prime time?

Patients with chronic kidney disease (CKD) are at increased risk of atrial fibrillation, stroke, and bleeding posing unique clinical challenges. Novel oral anticoagulants (NOACs) including dabigatran, rivaroxaban, and apixaban have become recognized as alternative therapy to Vitamin K Antagonists (VKA) regarding the prevention of venous thromboembolism (VTE) and reduce the risk of stroke in atrial fibrillation. However, the understanding of NOACs in CKD is still underdeveloped. This review summarizes recent literature on the efficacy and safety of NOACs in patients with CKD. Studies focusing on patients with moderate kidney disease were drawn from post hoc analyses from three major NOAC trials, meta-analyses, and postmarketing surveillance studies. Cumulatively, these studies continue to demonstrate NOACs as equivalent if not superior therapies to VKAs in regards to both efficacy and safety. These studies are limited by small sample sizes as well as a lack of direct comparison between NOACs. The role of NOACs in managing VTE and atrial fibrillation is increasing. Current research suggests that NOACs are at least as efficacious and well tolerated as VKAs. More research is required to elucidate which NOAC is preferable in the clinical setting.

A critical reappraisal of the treatment modalities of normal appearing thoracic aorta mural thrombi

Mural thrombus in non-atherosclerotic or aneurysmatic thoracic aorta is a relatively uncommon entity. Currently there is no consensus on the appropriate therapeutic algorithm of its management. We aim to present the current knowledge on the treatment of thoracic aorta mural thrombi (TAMT) in minimally atherosclerotic vessels and we hope that the juxtaposed discussions will shed light on the uncharted waters regarding this rare syndrome. The MEDLINE/PubMed database was searched for publications with the medical subject "aortic mural thrombus" and keywords "thoracic", "embolism", "normal vessel", "minimally atherosclerotic vessel" or "treatment". We restricted our search to English language, till January 2017. The electronic literature search yielded 23 reports that were deemed appropriate for further analysis. Anticoagulation is the standard of care for the treatment of the thrombus whereas surgical and interventional treatment seems to be related with increased mortality and lower recurrence rates. TAMT treatment is controversial. Anticoagulants are the mainstay of treatment but surgery seems to gain ground in several settings as an only therapy or a combined treatment modality. More data are needed on the role of novel oral anticoagulants and endografts.

Management strategies for atrial fibrillation.

Atrial fibrillation is the most prevalent cardiac arrhythmia, affecting 10% of those aged over 80 years. Despite multiple treatment options, it remains an independent prognostic marker of mortality due to its association with clinical sequelae, particularly cerebrovascular events. Management can be broadly divided into treatment of the arrhythmia, via rhythm or rate control, and stroke thromboprophylaxis via anticoagulation. Traditional options for pharmacotherapy include negatively chronotropic drugs such as β-blockers, and/or arrhythmia-modifying drugs such as amiodarone. More recently, catheter ablation has emerged as a suitable alternative for selected patients. Additionally, there has been extensive research to assess the role of novel oral anticoagulants as alternatives to warfarin therapy. There is mounting evidence to suggest that they provide comparable efficacy, while being associated with lower bleeding complications. While these findings are promising, recent controversies have arisen with the use of novel oral anticoagulants. Further research is warranted to fully elucidate mechanisms and establish antidotes so that treatment options can be appropriately directed.

‘The role of novel oral anticoagulants in patients undergoing cryoballoon ablation for atrial fibrillation’

AimPeri-procedural thromboembolic (TE) and hemorrhagic events are complications of major concern for patients undergoing cryoballoon (CB) ablation for atrial fibrillation (AF).While peri-procedural anticoagulation management could decrease the incidence of these complications, data on CB ablation are scarce. The role of novel oral anticoagulants (NOACs) has not been thoroughly tested in this population. MethodsIn the present study, we sought to assess acute peri-procedural complications in patients undergoing CB ablation for AF under different anticoagulation regimens; anticoagulation administration was performed according to the CHA2DS2-VASc score guidelines. To the best of our knowledge, this is the first study that compares 1) uninterrupted warfarin, 2) bridging therapy with low molecular weight heparin (LMWH), 3) aspirin and 4) NOACs in this subgroup of patients. ResultsNOACs were as effective as uninterrupted warfarin in terms of bleeding complications and TE events. Surprisingly, the aspirin group had more hemorrhagic complications than both the warfarin and NOACs groups. ConclusionIn the current study, the use of NOACs was an effective and safe approach in CB ablation.

Role of Novel Oral Anticoagulants in the Treatment of Antiphospholipid Syndrome.

Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis or pregnancy loss with persistent positive antibodies. Standard treatment for APS with history of thromboembolism is heparin or low-molecular-weight heparin followed by a vitamin K antagonist (VKA). Novel oral anticoagulants (NOACs) could be effective in patients with APS, but none carry indications for treatment related to APS. Clinical Evidence: Five case reports or series with rivaroxaban and dabigatran suggest thrombotic events occur most often in the higher risk population (arterial thrombosis and/or triple positive antibodies) or in patients who had recurrent VTEs on warfarin therapy. An observational cohort in 26 APS patients using dabigatran or rivaroxaban described a recurrent thrombotic event in only 1 patient after 8 months of treatment. The event-free survival rate was 87.9% at 12 months. Three controlled clinical trials are underway to evaluate the thrombotic risk of NOACs (RAPS, TRAPS, and ASTRO-APS). Discussion: There are no completed studies that evaluate the use of NOACs in APS compared to VKAs. One major disadvantage of the NOACs is the limited availability of reversal agents for patients with a major bleeding episode. An increased risk of thrombotic events is associated with arterial occlusions and triple antibody positivity APS with both warfarin and NOACs; this is currently being researched in the TRAPS study. Conclusion: Based on current available evidence, VKAs remain the standard of care in the treatment of APS. Results of ongoing trials may offer more guidance on how to appropriately use NOACs for patients with APS.

Are Some Anticoagulants More Equal Than Others? - Evaluating the Role of Novel Oral Anticoagulants in AF Ablation.

Left atrial ablation strategies are being increasingly performed as a Class 1 therapeutic indication for drug refractory paroxysmal atrial fibrillation (AF). Traditionally AF ablation has been performed with patients on uninterrupted warfarin therapy, however over the last few years, novel oral anticoagulants (NOACs) have emerged as attractive alternatives to warfarin in order to reduce stroke risk due to AF. NOACs are therefore increasingly being used instead of warfarin in the management of AF. There is also mounting evidence mainly in the form of small randomised studies and meta-analysis that have demonstrated that the use of NOACs for AF ablation is efficacious, safe and convenient. However the peri-procedural dosing protocols used in various studies especially in terms of whether NOAC use is interrupted or uninterrupted during AF ablation, have significant inter-operator and inter-institution variability. Currently there is also a lack of randomised controlled trials to validate the data obtained from meta-analyses. There is also evidence that use of NOACs may increase the requirement of unfractionated heparin during the procedure. This review article shall examine the currently available evidence-base, appraise the gaps in the current evidence and also underscore the need for larger randomised clinical trials in this rapidly developing field.

The Role Of NOACs in Atrial Fibrillation Management: A Qualitative Study.

Patients with atrial fibrillation (AF) benefit from anticoagulation to reduce stroke risk. However, 30-60% of patients with AF are not anticoagulated. This study explored physicians' reasons for under-treatment of AF, focusing on the role of the novel oral anticoagulants (NOACs). We interviewed primary care physicians and cardiologists involved in AF management in a variety of practice settings. We conducted interviews using a semi-structured format and analyzed the data using the Framework Method. Four themes emerged. First, the likelihood of physicians to prescribe NOACs depends upon their willingness to try new medications and their successful experience with them. Second, physicians typically balance the benefits and risks of anticoagulation in AF patients, although not always accurately. Third, patient convenience and preferences, as well as physician convenience, are important when considering anticoagulation. Finally, concerns regarding the out-of-pocket cost of NOACs deter many physicians from prescribing them. The persistence of under-treatment in AF despite the availability of effective therapies suggests that new strategies are needed to improve physician knowledge and practice. These strategies should enhance physician awareness of AF under-treatment, emphasize accurate assessment of bleeding risk among AF patients, compare the safety, efficacy, and convenience of NOACs relative to warfarin, and address physician concerns regarding the out-of-pocket cost of NOACs. Guidelines and decision supports which promote physician knowledge in these areas have the potential to increase oral anticoagulant use and reduce preventable morbidity and mortality.

Left Atrial Appendage and Closure: Who, When, and How.

Patients with nonvalvular atrial fibrillation have a 4- to 5-fold increase in strokes and that rhythm may be responsible for 15% to 20% of all strokes, particularly in the elderly. In this setting, thrombus in the left atrial appendage has been found to be the source of stroke in 90% of cases. Although oral anticoagulants have been found effective in reducing stroke rates, for a variety of issues, they may only be used in 40% to 50% of patients at increased risk for stroke. Given pathophysiology of stroke, site-specific therapy directed at left atrial appendage occlusion has been now studied for stroke prevention, and one device is FDA approved (Watchman). A meta-analysis of 2 randomized clinical trials and 2 registries with this device documented the following: (1) patients receiving the device had significantly fewer hemorrhagic strokes (hazard ratio 0.22, P=0.004); (2) a significant reduction in cardiovascular or unexplained death (hazard ratio 0.48, P=0.004); (3) more ischemic strokes in the device group; however, when periprocedural events were excluded, the difference was not significant; and (4) a significant reduction in nonprocedural bleeding with the device (hazard ratio 0.51, P=0.006) versus control. At present, the only device approved in the United States is indicated in patients with nonvalvular atrial fibrillation with acceptable anatomy who are at increased risk for stroke and would be candidates for anticoagulation in whom there is concern about the risk/benefit ratio for chronic anticoagulation. Unresolved issues include optimal patient selection criteria, the role of devices in patients in whom anticoagulation is contraindicated, and the relative role of novel oral anticoagulants versus the device which has not been tested in randomized trials.

Role of novel oral anticoagulants in the management and prevention of venous thromboembolism

Role of novel oral anticoagulants in the management and prevention of venous thromboembolism

Role of Novel Oral Anticoagulants in Primary and Secondary Thromboprophylaxis in Cancer

The development of venous thromboembolism is one of the major causes of morbidity and mortality in patients with cancer. The standard treatment of deep venous thrombosis or pulmonary embolism occurring in patients with active malignancy remains the use of low molecular weight heparins. However, in clinical practice, practitioners are frequently asked about the efficacy and safety of various new oral anticoagulants in cancer patients. In the United States, there are currently 4 different novel oral anticoagulants commercially available with the indication of the treatment of acute venous thromboembolism. These include dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). Use of these new medications is appealing due to the ease of administration, avoidance of injections, ability to use in patients with decreased renal or liver function, and consistent efficacy without fooddrug interactions. Currently, the only available data for the use of these new oral anticoagulants in cancer patients is from subgroup analysis of larger studies with no statistical significance. However, this preliminary data is encouraging that the novel oral anticoagulants may be effective and safe for primary and secondary prevention of venous thromboembolism in cancer patients. Further clinical trials are greatly needed for the head-tohead comparison of these novel oral anticoagulants versus low molecular weight heparins. Although the routine use of novel oral anticoagulants for the prevention or treatment of venous thromboembolism in cancer patients cannot be recommended at this time, we strongly support the development of Phase III trials assessing their efficacy and safety in patients with active malignancies compared to the current standard of care treatment with low molecular weight heparin.

NOAC in acute coronary syndrome and AF?

Cardiovascular disease remains a major cause of morbidity and mortality in developed countries. New treatments, in the form of novel oral anticoagulants (NOAC) that reduce thrombotic risk are now available for patients with atrial fibrillation (AF) or acute coronary syndrome (ACS). Warfarin has been the cornerstone of thromboprophylaxis in patients with AF, but treatment is cumbersome, inconvenient and often unreliable, with fluctuating time in therapeutic range. Thrombotic events also continue to occur in a significant number of ACS patients despite antiplatelet therapy. Thus there is an unfilled need to reduce thrombotic events in ACS and AF patients. NOAC comprise direct factor Xa inhibitors (apixaban, rivaroxaban, darexaban, edoxaban), direct thrombin inhibitors (dabigatran) and PAR-1 antagonists (vorapaxar, atopaxar). In this review, we compare and contrast NOACs and review their individual and specific clinical trial database in ACS and AF. In the setting of ACS, the role of NOAC is unclear, as any reduction in ischemic events appears to be offset by hemorrhagic risk. However, NOAC have a definite place in the treatment of patients with non-valvular AF, where they are at least as effective, if not superior to warfarin.

Anticoagulation in Patients Aged ≥75years with Atrial Fibrillation: Role of Novel Oral Anticoagulants.

Atrial fibrillation (AF) is an important cause of preventable, disabling stroke and is increasingly prevalent with advancing age. As life expectancies increase around the world, AF-related stroke is a growing global public health concern. Most AF patients are elderly (≥75 years old) and increasing age is a consistent independent risk factor for AF-associated stroke. Warfarin anticoagulation is highly effective for stroke prevention in AF patients, but is underutilized especially in the elderly. Although elderly patients are at increased risk of hemorrhage with oral anticoagulants, the benefit for ischemic stroke reduction exceeds the risk of hemorrhage for most elderly patients. Consequently, age alone should not be considered a contraindication for anticoagulation. Novel oral anticoagulants such as dabigatran, rivaroxaban and apixaban are at least as effective as warfarin in preventing strokes in patients with AF. Relative to warfarin, these novel agents reduce the risk of intracranial hemorrhage, the most devastating complication of anticoagulation therapy in elderly AF patients. The novel oral anticoagulants are especially appealing for stroke prevention in elderly patients with AF.

Management of Venous Thromboembolism in Patients with Advanced Gastrointestinal Cancers: What Is the Role of Novel Oral Anticoagulants?

Venous thromboembolism (VTE) is a frequent complication of gastrointestinal cancers that increases morbidity and may impact mortality. Low-molecular-weight heparins (LMWHs) and vitamin K antagonists (VKAs) are standard anticoagulation options for the ambulatory gastrointestinal cancer patient with VTE, but both of these agents are challenging to use for various reasons. Novel oral anticoagulants (NOAs) are new, orally available anticoagulants designed to be easier to administer with more reliable pharmacokinetics that eliminate the need for frequent monitoring of various laboratory parameters. This paper reviews the existing efficacy and safety data for the use of NOAs dabigatran etexilate, rivaroxaban, and apixaban and discusses the potential role of these agents in the management of gastrointestinal cancer-related VTE.

Prevention and Treatment of Venous Thromboembolism and Pulmonary Embolism: The Role of Novel Oral Anticoagulants

Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke. Clinicians are often summoned to make challenging decisions for the prevention and treatment of high risk patients with an unpredicted outcome, often relying on data that are less than definitive. During the last decades, heparins (unfractionated and low molecular weight heparins) as well as vitamin K antagonists, such as warfarin, and indirect Xa inhibitors, such as fontaparinux, are the cornerstone for the prevention and treatment of patients with venous thromboembolism. However, the traditionally used anticoagulants have several drawbacks that may limit their efficacy and use in every day clinical practise. The newly developed oral anticoagulants, belonging to the categories of direct thrombin inhibitors (DTIs) and direct Xa inhibitors, have emerged as promising agents with remarkable efficacy, concentrating many parameters of an ideal anticoagulant. Rivaroxaban, dabigatran and apixaban are the most studied agents, while a plethora of others are investigated in clinical trials of different phases and are expected to reach the market in the following years. The purpose of this review is to summarize the so far acquired knowledge on these agents, to report briefly some of their pharmacodynamic and pharmacokinetic properties and to focus on their role in the treatment and prevention of venous thromboembolism.