Hemopericardium with subsequent cardiac tamponade secondary to rivaroxaban treatment: a case report

Abstract Background The use and utility of novel oral anticoagulants has been increasing in clinical practice due to their relatively lower incidence of side effects such as intracranial haemorrhage, particularly in the elderly, when compared with vitamin K antagonists. Rivaroxaban is a factor Xa and prothrombinase inhibitor indicated for stroke and venous thromboembolism prophylaxis in non-valvular atrial fibrillation as well as treatment of venous thromboembolism. Case summary A patient with history of paroxysmal atrial fibrillation on Rivaroxaban presented with generalized malaise, lightheadedness, and dizziness. The patient was found to be in profound cardiogenic shock despite unremarkable cardiac enzymes. Electrocardiogram revealed rate controlled atrial fibrillation and T-wave inversions in the inferolateral leads without associated electrical alternans. Bedside echocardiogram revealed a large pericardial effusion consistent with cardiac tamponade physiology. Following anticoagulation reversal, the patient underwent urgent pericardiocentesis yielding haemorrhagic fluid, with subsequent improvement in haemodynamic status. Despite the presence of retroperitoneal lymphadenopathy on previous computed tomography of the abdomen and concern for underlying malignant effusion secondary to lymphoma, cytology of the fluid revealed no evidence of malignant cells and follow-up flow cytometry and bone marrow biopsy were unremarkable. Discussion While hemopericardium is not listed as a known side effect of Rivaroxaban, previous cases of hemopericardium secondary to Rivaroxaban have been described in the literature secondary to pre-disposing risk factors including CYP450 drug interactions or cardiac device implantations. In this case, the patient experienced a spontaneous hemopericardium on Rivaroxaban without any previously elucidated risk factors or evidence of malignancy.

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The NOACs: clinical pharmacology

ESC CardioMed ◽

10.1093/med/9780198784906.003.0056 ◽

2018 ◽

pp. 268-272

Author(s):

Jeffrey Weitz

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Active Site ◽

Randomized Clinical Trials ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

Vitamin K Antagonist ◽

Phase Iii ◽

High Affinity

The limitations of vitamin K antagonists prompted the development of new oral anticoagulants that could be administered in fixed doses without routine coagulation monitoring. Focusing on thrombin and factor Xa because of their prominent roles in coagulation, structure-based design led to the development of small molecules that bind to the active site pockets of these enzymes with high affinity and specificity. Four non-vitamin K antagonist oral anticoagulants are now licensed: dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In phase III randomized clinical trials that included over 100,000 patients these agents have proven to be at least as effective as vitamin K antagonists for prevention of stroke in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less bleeding, particularly less intracranial bleeding.

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The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420923528 ◽

2020 ◽

Vol 25 (5) ◽

pp. 391-398

Author(s):

Fabiana Lucà ◽

Simona Giubilato ◽

Stefania Angela Di Fusco ◽

Angelo Leone ◽

Stefano Poli ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Antiplatelet Therapy ◽

Oral Anticoagulant ◽

Acute Coronary Syndromes ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Clinical Scenarios ◽

Coronary Syndromes

Antithrombotic drugs, which include antiplatelets and anticoagulants, are effective in prevention and treatment of many cardiovascular disorders such as acute coronary syndromes, stroke, and venous thromboembolism and are among the drugs most commonly prescribed worldwide. The advent of direct oral anticoagulants, which are safer alternatives to vitamin K antagonists and do not require laboratory monitoring, has revolutionized the treatment of nonvalvular atrial fibrillation and venous thromboembolism. The combination of oral anticoagulant and antiplatelet therapy is required in many conditions of great clinical impact such as the coexistence of atrial fibrillation and coronary artery disease, with indication to percutaneous coronary intervention. However, strategies that combine anticoagulant and antiplatelet therapies lead to a significant increase in bleeding rates and it is crucial to find the right combination in the single patient in order to optimize the ischemic and bleeding risk. The aim of this review is to explore the evidence and controversies regarding the optimal combination of anticoagulant and antiplatelet therapy through the consideration of past dogmas and new perspectives from recent clinical trials and to propose a tailored therapeutic approach, according to specific clinical scenarios and individual patient characteristics. In particular, we separately explored the clinical settings of stable and acute coronary syndromes and percutaneous revascularization in patients with atrial fibrillation.

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Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board

Netherlands Heart Journal ◽

10.1007/s12471-020-01424-y ◽

2020 ◽

Vol 28 (10) ◽

pp. 504-513 ◽

Cited By ~ 1

Author(s):

B. A. Mulder ◽

J. ten Berg ◽

H. ten Cate ◽

N. van Es ◽

M. E. W. Hemels ◽

...

Keyword(s):

Atrial Fibrillation ◽

Treatment Guidelines ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Daily Practice ◽

Advisory Board ◽

Vascular Surgeon ◽

Clinical Scenarios

Abstract The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

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Advances in Atrial Fibrillation-related Stroke Prevention

European Neurological Review ◽

10.17925/enr.2014.09.02.122 ◽

2015 ◽

Vol 9 (2) ◽

pp. 122

Author(s):

Pierre Amarenco ◽

Werner Hacke ◽

Bo Norrving ◽

Natalia Rost ◽

◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Anticoagulant Therapy ◽

Stroke Prevention ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Factor Xa ◽

Haemorrhagic Stroke ◽

Bleeding Events ◽

Patients At Risk

In patients with atrial fibrillation (AF) the risk of stroke is substantially increased, especially in those who are elderly (over 75 years) or have risk factors such as previous stroke, heart failure or hypertension. Stroke outcomes are also generally much worse in those with AF. Current guidelines indicate that any patient with AF and risk factors for stroke should receive anticoagulant therapy to limit their stroke risk. Despite these established recommendations, only 50 % of patients at risk receive anticoagulation with a vitamin K antagonist (VKA) and only 50 % of those are within the therapeutic range, indicating lack of adherence to the guidelines. Withholding anticoagulant therapy is mainly left to an individual physician’s choice, as shown in the ongoing GARFIELD registry of AF stroke prevention practice. Many physicians fear the risk of intracranial haemorrhage (ICH) for which outcomes remain poor. Recent clinical studies have shown that the non-VKA oral anticoagulants (NOACs) (apixaban, rivaroxaban, dabigatran and edoxaban) significantly reduce the risk of ICH and other bleeding events, while having non-inferior stroke prevention to warfarin. Use of these drugs, limiting exposure to aspirin and alcohol and controlling blood pressure have been shown to minimise ICH risk in large clinical trials and meta-analyses. Recent data from the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation (ENGAGE AF)-TIMI 48 study showed that the factor Xa inhibitor edoxaban was non-inferior to well-managed warfarin for reducing all stroke risk, and significantly reduced haemorrhagic stroke, major bleeding, ICH and death. These findings further support the case for using NOAC therapy for stroke prevention in patients with AF and risk factors for stroke.

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Pros and cons of new oral anticoagulants

Hematology ◽

10.1182/asheducation-2013.1.464 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 464-470 ◽

Cited By ~ 106

Author(s):

Kenneth A. Bauer

Keyword(s):

Venous Thromboembolism ◽

Vitamin K Antagonists ◽

Dabigatran Etexilate ◽

Oral Anticoagulants ◽

Factor Xa ◽

Rapid Onset ◽

New Oral Anticoagulants ◽

Therapeutic Class ◽

Pros And Cons ◽

Additional Agent

Abstract The availability of new oral anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated. NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating efficacy and safety that are at least as good, if not better, than warfarin (for stroke prevention in atrial fibrillation and treatment and secondary prevention of venous thromboembolism) or low-molecular-weight heparin, which is injectable (for initial treatment of venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee arthroplasty). However, the adoption of this new therapeutic class into clinical practice has been slower than expected due to several factors including concerns regarding medication adherence without laboratory monitoring, uncertainty about dosing in some patient populations (eg, renal dysfunction, marked extremes of body weight), and higher drug costs compared with warfarin. Other issues are the current absence of specific antidotes for NOACs and assays to measure drug levels at most centers. The indications for NOACs on the market will expand and at least one additional agent (edoxaban) will likely gain approval within the next 2 years. As practitioners gain familiarity with the drugs and healthcare systems adapt to their use, NOAC use will increase substantially over time. Warfarin, however, will continue to be an appropriate anticoagulant choice for many patients.

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Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors

Stroke ◽

10.1161/strokeaha.120.032704 ◽

2021 ◽

Author(s):

Lamiae Grimaldi-Bensouda ◽

Jean-Yves Le Heuzey ◽

Jean Ferrières ◽

Didier Leys ◽

Jean-Marc Davy ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Vitamin K ◽

Oral Anticoagulant ◽

Hemorrhagic Stroke ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Clinical Risk Factors ◽

Direct Oral Anticoagulant

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

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Direct oral anticoagulants and venous thromboembolism

European Respiratory Review ◽

10.1183/16000617.0025-2016 ◽

2016 ◽

Vol 25 (141) ◽

pp. 295-302 ◽

Cited By ~ 10

Author(s):

Massimo Franchini ◽

Pier Mannuccio Mannucci

Keyword(s):

Venous Thromboembolism ◽

Vitamin K Antagonists ◽

Dabigatran Etexilate ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Thrombin Inhibitors ◽

Vein Thrombosis ◽

Direct Anticoagulants ◽

Deep Vein

Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

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Broadening the Categories of Patients Eligible for Extended Venous Thromboembolism Treatment

Thrombosis and Haemostasis ◽

10.1055/s-0039-3400302 ◽

2019 ◽

Vol 120 (01) ◽

pp. 014-026 ◽

Cited By ~ 3

Author(s):

Marc Schindewolf ◽

Jeffrey Ian Weitz

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thromboembolism ◽

Profile Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Specific Risk ◽

Increased Risk

AbstractTraditionally, venous thromboembolism (VTE) resulting from major transient risk factors (e.g., surgery or trauma) or a major persistent risk factor such as cancer, has been defined as being provoked, whereas unprovoked VTE encompasses events without an identifiable cause. These categorizations influence anticoagulant treatment duration; unlike VTE provoked by major transient risk factors, extended anticoagulation beyond 3 months is advised for patients with cancer or unprovoked VTE due to risk persistence after treatment cessation. However, some patients with VTE provoked by minor transient or minor persistent risk factors may also be candidates for extended anticoagulation therapy due to the continuing risk of recurrence. In patients who require extended therapy, vitamin K antagonists (VKAs) are effective but are associated with an increased risk of bleeding and various treatment burdens (e.g., anticoagulation monitoring and dose adjustment). Evaluations of extended VTE treatment with the less-burdensome direct oral anticoagulants such as apixaban, dabigatran, edoxaban, and rivaroxaban show that they are at least as safe and effective as VKAs in a broad range of patients. In addition, apixaban and rivaroxaban offer more than one dosing option, allowing tailoring of treatment to the patient's specific risk factor profile. Analysis of more granular definitions for risk factor groupings has also yielded vital information on the most appropriate strategies for the treatment of patients with specific risk factors, highlighting that extended anticoagulation treatment may benefit those with minor transient and persistent environmental and nonenvironmental risk factors who commonly receive shorter-duration therapy.

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P472Cerebral thromboembolic risk in atrial fibrillation ablation: a direct comparison of vitamin K antagonists versus non-vitamin K-dependent oral anticoagulants

EP Europace ◽

10.1093/europace/euaa162.117 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

A M Petzl ◽

M Derndorfer ◽

G Kollias ◽

K Moroka ◽

J Aichinger ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Cerebral Lesions ◽

Cerebral Magnetic Resonance Imaging ◽

Af Ablation ◽

Significant Difference ◽

Independent Risk Factors

Abstract Aims Cerebral thromboembolic events are well-known complications of pulmonary vein isolation (PVI) and can manifest as stroke or silent cerebral embolic lesions. Over the last years, the preferred oral anticoagulation in atrial fibrillation (AF) shifted from vitamin K antagonists (VKA) to non-vitamin K-dependent oral anticoagulants (NOAC). The aim of this study was to compare the incidence of cerebral embolic lesions after AF ablation in patients on VKA versus patients on NOAC, and to identify corresponding clinical and procedural risk factors. Methods A total of 421 patients undergoing PVI (by radiofrequency catheter or cryoballoon) were prospectively included into the study. Of these, 43.7% were on VKA and 56.3% on NOAC treatment. In the NOAC group 38% of patients had an interruption of anticoagulation for 24-36 hours. All patients underwent pre- and postprocedural cerebral magnetic resonance imaging. Results Periprocedural cerebral lesions occurred in 13.1% overall. Of these, three (0.7%) resulted in symptomatic cerebrovascular accidents. Incidence of cerebral lesions was significantly higher in patients on NOAC compared to VKA (16% vs. 9.2% respectively, p = 0.04), as well as in patients that had intraprocedural cardioversions compared to no cardivoersions (19.5% vs. 10.4% respectively, p = 0.03). In multivariate analysis both parameters were found to be independent risk factors for cerebral embolism. No significant difference between interrupted and uninterrupted NOAC administration could be detected. Conclusions In patients undergoing AF ablation, we identified the use of NOAC and intraprocedural cardioversion as independent risk factors for the occurrence of periprocedural cerebral embolic lesions. Abstract Figure. Incidence of cerebral embolic lesions

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Emerging anticoagulants for the treatment of venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th06-05-0234 ◽

2006 ◽

Vol 96 (09) ◽

pp. 274-284 ◽

Cited By ~ 47

Author(s):

Jeffrey Weitz

Keyword(s):

Venous Thromboembolism ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Factor Xa ◽

New Drugs ◽

New Anticoagulants ◽

Postphlebitic Syndrome ◽

Long Acting ◽

Two Stages

SummaryAnticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into two stages. Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists,such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This paper i) reviews the pharmacology of these agents, ii) outlines their potential strengths and weaknesses, iii) describes the results of clinical trials with these new drugs, and iv) identifies the evolving role of new anticoagulants in the management of VTE.

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