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1.
Dual versus triple antithrombotic therapy: is there a role for direct oral anticoagulants in arterial thrombosis?
Garcia-Ropero, A, Santos-Gallego, CG, Zafar, MU, Badimon, JJ
Drugs of today (Barcelona, Spain : 1998). 2019;(3):197-214
Abstract
The number of patients receiving dual antiplatelet therapy with an additional indication for long-term oral anticoagulation has substantially increased over time. This population is facing an unacceptable risk of bleeding events, particularly among elderly individuals, who are especially vulnerable to complications. Further strategies to minimize this bleeding risk, including various drug combinations, different dosage regimens and even numerous attempts to find the appropriate duration of the treatment, have been evaluated in a multitude of randomized control trials. Moreover, the recent incorporation of the direct oral anticoagulants (DOACs) to the therapeutic armamentarium may represent an alternative to treat such patients, since they have demonstrated to be noninferior to the classic vitamin K antagonists and with lower bleeding rates. The aim of this review is to summarize the most recent literature on the use of DOACs in patients with an indication for dual antiplatelet therapy (mostly subjects with coronary artery disease) and also an established indication for chronic anticoagulation (chiefly individuals with nonvalvular atrial fibrillation). The role of DOACs in ischemic heart disease alone is also discussed.
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The changing face of venous thromboembolism management in England.
Ramagopalan, SV, Carroll, R, Ulvestad, M, Mehmud, F, Alikhan, R
Future cardiology. 2019;(3):183-185
Abstract
Aim: Venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism, poses a global disease burden. Vitamin K antagonists have traditionally been the mainstay of treatment; however, the non-vitamin K oral anticoagulants (NOACs) are emerging as an alternative. The relative use of these treatment classes in the real world is unknown. Patients & methods: We performed a retrospective study using data from the UK Clinical Practice Research Datalink to understand VTE treatment patterns. Results: NOACs have unseated vitamin K antagonist as the main form of VTE patient treatment in England. Conclusion: The data highlight how comfortable physicians have become in using NOACs to treat VTE in England and it is likely that the increasing use of NOACs will continue.
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3.
Antithrombotic medications and their impact on fibrin clot structure and function.
Undas, A, Zabczyk, M
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2018;(4)
Abstract
Fibrin constitutes a major protein component of intravascular thrombi in all locations. Fibrin formation and its functions are essential for physiological hemostasis and the pathologic thrombosis. Formation of dense fibrin networks which are relatively resistant to lysis is observed in patients with venous or arterial thromboembolism, including myocardial infarction, ischemic stroke and venous thromboembolism. Measures of clot characteristics, in particular clot permeability and clot lysis time, may predict arterial and venous recurrent thromboembolic events. Medications, including vitamin K antagonists (VKA), direct oral anticoagulants (DOAC), and parenteral direct or indirect thrombin or activated factor X inhibitors increase clot permeability, reflecting fibrin network density, in association with enhanced efficiency of fibrinolysis. These effects are only in part related to decreased thrombin generation. There is evidence that aspirin can also favorably alter fibrin clot properties probably through acetylation of fibrinogen. No such effects were observed for P2Y12 inhibitors. Of note, plasma fibrin clot permeability has been shown to predict adverse clinical outcomes in patients receiving oral anticoagulants, which might have practical implications. The current review summarizes data on effects of antithrombotic agents on fibrin clot phenotype in cardiovascular disease.
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4.
Intravenous tPA (Tissue-Type Plasminogen Activator) in Patients With Acute Ischemic Stroke Taking Non-Vitamin K Antagonist Oral Anticoagulants Preceding Stroke.
Jin, C, Huang, RJ, Peterson, ED, Laskowitz, DT, Hernandez, AF, Federspiel, JJ, Schwamm, LH, Bhatt, DL, Smith, EE, Fonarow, GC, et al
Stroke. 2018;(9):2237-2240
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Abstract
Background and Purpose- Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods- A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized. Results- We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5-14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0-2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12-2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08-1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45-14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions- These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.
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Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.
Richardson, PG, Triplett, BM, Ho, VT, Chao, N, Dignan, FL, Maglio, M, Mohty, M
Expert review of clinical pharmacology. 2018;(2):113-124
Abstract
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable condition associated with endothelial-cell damage due to conditioning for hematopoietic stem-cell transplantation (HSCT) or chemotherapy without HSCT. Mortality in patients with VOD/SOS and multi-organ dysfunction (MOD) may be >80%. Areas covered: Defibrotide is the only approved drug for the treatment of severe hepatic VOD/SOS after HSCT in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction in the United States. Its efficacy in patients with VOD/SOS with MOD post-HSCT was demonstrated in a clinical-trial program that included a historically controlled treatment study, a phase 2 trial, and a large T-IND expanded-access program that also included patients without MOD and who received chemotherapy without HSCT. Expert commentary: Defibrotide appears to protect endothelial cells and restore the thrombolytic-fibrinolytic balance. It addresses a significant clinical need and has demonstrated favorable Day +100 survival and overall adverse-event rates that seem similar to control groups receiving supportive care alone. Currently, defibrotide is under investigation for the prevention of VOD/SOS in high-risk pediatric and adult patients.
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[Oral anticoagulants in elderly patients with coronary artery disease and atrial fibrillation].
Gallet, R, Teiger, E
Annales de cardiologie et d'angeiologie. 2018;(6):404-410
Abstract
Anti-thrombotic management of percutaneous coronary intervention and atrial fibrillation relies on dual antiplatelet therapy and anticoagulation respectively. Because of people ageing, the coexistence of coronary artery disease and atrial fibrillation is increasing. This coexistence raises concerns about the anti-thrombotic strategy, particularly about the association of dual antiplatelet therapy and anticoagulation, known as triple therapy. This triple therapy is responsible for a dramatic increase in bleeding risk (3-4 fold) especially in elderlies. However, older patients are also at increased risk of ischemic events. In this setting, dual anti-thrombotic strategies combining non-vitamin K oral anticoagulants and a P2Y12 inhibitor have been developed. These strategies provide a net benefit by reducing bleeding events. Therefore, they are becoming an attractive alternative, especially for frailer patient. This article reviews the rational, risks and strategies of anti-thrombotic therapy in elderly people with coronary artery disease and atrial fibrillation.
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Antithrombotic therapy management of adult and pediatric cardiac surgery patients.
Baumann Kreuziger, L, Karkouti, K, Tweddell, J, Massicotte, MP
Journal of thrombosis and haemostasis : JTH. 2018;(11):2133-2146
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Abstract
Despite the development of catheter-based interventions for ischemic and valvular heart disease, hundreds of thousands of people undergo open heart surgery annually for coronary artery bypass graft (CABG), valve replacement or cardiac assist device implantation. Cardiac surgery patients are unique because therapeutic anticoagulation is required during cardiopulmonary bypass. Developmental hemostasis and altered drug metabolism affect management in children. This narrative review summarizes the current evidence-based and consensus guidelines regarding perioperative, intraoperative and postoperative antithrombotic therapy in patients undergoing cardiac surgery. Anticoagulation preoperatively is required in the setting of cardiac arrhythmias, prior valve replacement or history of venous thromboembolism. In patients with ischemic heart disease, aspirin is continued in the perioperative period, whereas oral P2Y12 antagonists are withheld for 5-7 days to reduce the risk of perioperative bleeding. Intraoperative management of cardiopulmonary bypass in adults and children includes anticoagulation with unfractionated heparin. Variability in dose-response to heparin and influence of other medical conditions on dosing and reversal of heparin make intraoperative anticoagulation challenging. Vitamin K antagonist therapy is the standard anticoagulant after mechanical heart valve or left ventricular assist device (LVAD) implantation. Longer duration of dual antiplatelet therapy is recommended after CABG if patients undergo surgery because of acute coronary syndrome. Antiplatelet therapy after LVAD implantation includes aspirin, dipyridamole and/or clopidogrel in children and aspirin in adults. A coordinated approach between hematology, cardiology, anesthesiology, critical care and cardiothoracic surgery can assist to balance the risk of thrombosis and bleeding in patients undergoing cardiac surgery.
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8.
Antithrombotic Therapy for Atrial Fibrillation and Coronary Disease Demystified.
Andrade, JG, Deyell, MW, Wong, GC, Macle, L
The Canadian journal of cardiology. 2018;(11):1426-1436
Abstract
Atrial fibrillation (AF) is a progressive chronic disease characterized by exacerbations and periods of remission. It is estimated that up to 20% to 30% of those with AF also have coronary artery disease (CAD), and 5% to 15% will require percutaneous coronary intervention (PCI). In patients with concomitant AF and CAD, management remains challenging and requires a careful and balanced assessment of the risk of bleeding against the anticipated impact on ischemic outcomes (AF-related stroke and systemic embolism, as well as ischemic coronary events). Oral anticoagulation (OAC) is indicated for the prevention of AF-related stroke and systemic embolism, whereas antiplatelet therapy is indicated for the prevention of coronary events. Each offers a relative efficacy benefit (dual antiplatelet therapy [DAPT] is more effective than OAC alone in reducing cardiovascular death, myocardial infarction, stent thrombosis, and ischemic coronary events in a population with acute coronary syndromes [ACS]), but with a relative compromise (DAPT is significantly inferior to OAC for the prevention of stroke/systemic embolism in an AF population at increased risk of stroke). The purpose of this review is to explore the current evidence and rationale for antithrombotic treatment strategies in patients with both AF and CAD. Specifically, there is a focus on how to best tailor the therapeutic choices (OAC and antiplatelet therapy) to individual patients based on their underlying coronary presentation.
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[Anti-Thrombotic Treatment of Patients with Peripheral Artery Disease (PAD)].
Espinola-Klein, C
Deutsche medizinische Wochenschrift (1946). 2018;(15):1060-1064
Abstract
Patients with peripheral artery disease are at high-risk for cardiovascular events. Anti-thrombotic treatment is very important for secondary prevention. In symptomatic patients single antiplatelet therapy with clopidogrel or Aspirin is recommended. After peripheral revascularisation transient dual antiplatelet therapy is widely used although there is only little evidence. Following peripheral bypass surgery most patients are treated with single antiplatelet therapy, in some cases (prostetic bypass grafts) dual antiplated therapy can be useful and selected patients with complex venous grafts might profit from anticoagulation with vitamin K antagonists.The recent publication of the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) study showed relevant reduction of MACE (Major Adverse Cariac Events) and MALE (Major Adverse Limb Events) for the combined therapy of rivaroxaban 2 × 2,5 mg compared to Aspirin 100 mg with increased risk for gastrointestinal bleeding. In the current VOYAGER PAD (Vascular Outcomes Study of Aspirin along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) study this concept is tested after peripheral revascularisation.
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10.
Anticancer Drug-Related Nonvalvular Atrial Fibrillation: Challenges in Management and Antithrombotic Strategies.
Tufano, A, Galderisi, M, Esposito, L, Trimarco, V, Sorriento, D, Gerusalem, G, Picardi, M, Lancellotti, P, Pane, F
Seminars in thrombosis and hemostasis. 2018;(4):388-396
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Abstract
Cancer patients may experience nonvalvular atrial fibrillation (AF) as a manifestation of cardiotoxicity. AF may be a direct effect of a neoplasm or, more often, appear as a postsurgical complication, especially after thoracic surgery. AF may also develop as a consequence of anticancer therapy (chemotherapy or radiotherapy), a condition probably underestimated. Cancer patients with AF require a multidisciplinary approach involving oncologists/hematologists, cardiologists, and coagulation experts. An echocardiogram should be performed to detect possible abnormalities of left ventricular systolic and diastolic function, as well as left atrial dilation and the existence of valvular heart disease, to determine pretest probability of sinus rhythm restoration, and identify the best treatment. The choice of antiarrhythmic treatment in cancer patients may be difficult because scanty information is available on the interactions between anticancer agents and antiarrhythmic drugs. A careful evaluation of the antithrombotic strategy with the best efficacy/safety ratio is always needed. The use of vitamin K antagonists (VKAs) may be problematic because of the unpredictable therapeutic response and high bleeding risk in patients with active cancer who are undergoing chemotherapy and who may experience thrombocytopenia and changes in renal or hepatic function. Low molecular weight heparins (in particular for short and intermediate periods) and non-VKA oral anticoagulants (NOACs) should be preferred. However, the possible pharmacological interactions of NOACs with both anticancer and antiarrhythmic drugs should be considered. Based on all these considerations, antiarrhythmic and anticoagulant therapy for AF should be tailored individually for each patient.