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1.
Double or triple antithrombotic therapy after coronary stenting and atrial fibrillation: A systematic review and meta-analysis of randomized clinical trials.
Andò, G, Costa, F
International journal of cardiology. 2020;:95-102
Abstract
AIMS: Double or triple antithrombotic therapy (DAT/TAT) including or excluding aspirin in association with oral anticoagulant and P2Y12 inhibitor are currently two available options in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). We evaluated efficacy and safety outcomes for DAT vs. TAT. METHODS AND RESULTS Four non-vitamin K oral anticoagulants (NOAC)-based randomized controlled trials comparing DAT vs. TAT with a total of 10,938 patients were pooled. Bleeding events occurred more frequently than ischemic events. DAT as compared to TAT was associated to an increased risk of stent thrombosis (RR 1.54, 95% CI 1.10-2.14; p = 0.03), myocardial infarction (RR 1.23, 95% CI 1.04-1.46; p = 0.03) and cardiovascular mortality (RR 1.09, 95% CI 1.01-1.19; p = 0.04) and to a reduced risk of ISTH major or clinically relevant non-major bleeding (RR 0.59, 95% CI 0.62-0.93; p = 0.03). A consistent effect was observed in all safety endpoints. Intracranial haemorrhage was numerically reduced by DAT. No difference for all-cause death was observed. CONCLUSION Antithrombotic treatment in patients with AF undergoing PCI represents a trade-off between ischemia and bleeding. A careful patient selection based on baseline ischemic and bleeding risk may optimize the net clinical balance in this population.
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2.
Tinzaparin Sodium Pharmacokinetics in Patients with Chronic Kidney Disease: Practical Implications.
Helfer, H, Siguret, V, Mahé, I
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020;(3):223-228
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Abstract
Low-molecular-weight heparins (LMWHs) are the mainstay of the prophylaxis and treatment of venous thromboembolism (VTE). Due to their renal elimination, the risk of accumulation with the related bleeding risk may represent a limitation for the use of LMWHs in patients with chronic kidney disease (CKD) as the risk of major bleeding is increased in patients with creatinine clearance (CrCl) < 30 mL/min, especially in patients with cancer. LMWH structure and molecular weight (MW) are heterogeneous among available agents. The elimination of tinzaparin, which has the highest mean MW among LMWHs, is less dependent on renal function as it is also metabolized through the reticuloendothelial system. A subcutaneous therapeutic dose of tinzaparin (175 IU/kg) once daily has been shown to cause no accumulation of anti-factor Xa activity in patients with CrCl ≥ 20 mL/min. Clinical experience from randomized controlled studies has shown no significant impact of CKD on bleeding risk in cancer patients receiving treatment doses of tinzaparin. This suggests that in these patients the use of treatment doses of tinzaparin does not require anticoagulation monitoring or dose adjustment.
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3.
Atrial Fibrillation in Heart Failure: Focus on Antithrombotic Management.
Obeidat, M, Burgess, M, Lip, GYH
Heart failure clinics. 2020;(1):107-120
Abstract
Heart failure (HF) and atrial fibrillation (AF), increasingly common in the aging population, are closely related and commonly found together. This article explores the relationship between AF and HF and the thromboembolic effect of these diseases. Morbidity and mortality are increased when the 2 conditions are seen together. Stroke risks are significant with AF and all subtypes of HF. This article suggests that all patients with AF and HF should be considered for anticoagulation. Current evidence suggests that non-vitamin K antagonist oral anticoagulants are effective and safe in AF and HF in comparison with warfarin.
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4.
[Antithrombotic therapy in cardiovascular diseases].
Marx, N
Deutsche medizinische Wochenschrift (1946). 2020;(14):947
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Systematic Literature Review of Randomized Trials Comparing Antithrombotic Therapy Following Revascularization Procedures in Patients With Peripheral Artery Disease.
Schindewolf, M, Beyer-Westendorf, J, Balradj, J, Bowrin, K, Huelsebeck, M, Briere, JB
Angiology. 2020;(9):773-790
Abstract
A systematic literature review was conducted to identify and summarize the clinical efficacy and safety of available antithrombotic therapies after peripheral endovascular or surgical revascularization in patients with peripheral artery disease (PAD). Five databases were searched using free-text and Emtree/Mesh terms for PAD, randomized controlled trials (RCTs), and antithrombotic therapies of interest (ie, single antiplatelet therapy, dual antiplatelet therapy, and vitamin K antagonists). Randomized controlled trials were eligible for inclusion if they assessed the risk of thrombotic events (ie, myocardial infarction, ischemic stroke, cardiovascular death, limb ischemia, or limb amputation) or safety profile (ie, minor, moderate, major, or fatal bleeding events) after revascularization. In total, 16 RCTs were identified. Only a few studies reported on treatment effects of the investigated therapies. Myocardial infarction, ischemic stroke, cardiovascular death, and amputation were reported in up to 2.3%, 2.3%, 5.6%, and 7.3% of patients, respectively. Bleeding events were observed in up to 8.4% (major) and 1.5% (fatal) of patients. Despite available treatments, patients with PAD undergoing revascularization remain at risk of thrombotic events. There is a need for new treatments that will help to optimize care for patients with symptomatic PAD undergoing revascularization.
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Comparative analysis of fibrinolytic properties of Alteplase, Tenecteplase and Urokinase in an in vitro clot model of intracerebral haemorrhage.
Keric, N, Döbel, M, Krenzlin, H, Kurz, E, Tanyildizi, Y, Heimann, A, König, J, Kempski, O, Ringel, F, Masomi-Bornwasser, J
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2020;(9):105073
Abstract
OBJECTIVE Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral and intraventricular haemorrhage (ICH and IVH). However, the MISTIE III and CLEAR III trial failed to show significant improvement of favourable outcomes. Besides experimental and clinical trials revealed neurotoxic effects of rtPA. The demand for optimization of fibrinolytic therapy persists. Herein, we used our recently devised clot model of ICH to systematically analyse fibrinolytic properties of rtPA, tenecteplase and urokinase. METHODS In vitro clots of human blood (size: 25 ml and 50 ml; age: 1.5 tenecteplase, 24 tenecteplase and 48 tenecteplase) were produced and equipped with a catheter into the clot core for drug delivery and drainage. Various doses of tenecteplase and urokinase with different treatment periods were examined (overall 117 clots), assessing the optimal dose and treatment time of these fibrinolytics. Clots were weighed before and at the end of treatment. These results were compared with clots treated with 1 mg rtPA or with 0.9% sodium chloride solution. RESULTS The optimal treatment scheme of tenecteplase was found to be 100 IU with an incubation time of 30 min, for urokinase it was 50 000 IU with an incubation time of 20 min. The relative clot end weight of tenecteplase and urokinase (31.3±11.9%, 34.8 ±7.7%) was comparable to rtPA (36.7±10.7%). Larger clots were more effectively treated with tenecteplase compared to the control group (P=0.0013). urokinase and tenecteplase had similar lysis rates in aged clots and 90 min clots. One and two repetitive treatments with tenecteplase were as effective as two and three cycles of urokinase. CONCLUSIONS In our in vitro clot model we could determine optimal treatment regimens of tenecteplase (100 IU, 30 min) and urokinase (50 000 IU, 20 min). Urokinase and tenecteplase were comparable in their fibrinolytic potential compared to 1mg rtPA in small clots and showed an effective lysis in aged clots. tenecteplase was more effective in larger clots.
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Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study.
De Vriese, AS, Caluwé, R, Pyfferoen, L, De Bacquer, D, De Boeck, K, Delanote, J, De Surgeloose, D, Van Hoenacker, P, Van Vlem, B, Verbeke, F
Journal of the American Society of Nephrology : JASN. 2020;(1):186-196
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Abstract
BACKGROUND Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation. METHODS Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000 µg thrice weekly during 18 months. Systemic dp-ucMGP levels were quantified to assess vascular vitamin K status. Cardiac and thoracic aorta calcium scores and pulse wave velocity were measured to evaluate VC progression. RESULTS Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm. CONCLUSIONS Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs.
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Meta-analysis Comparing Direct Oral Anticoagulants Versus Vitamin K Antagonists After Transcatheter Aortic Valve Implantation.
Ueyama, H, Kuno, T, Ando, T, Briasoulis, A, Fox, J, Hayashida, K, Takagi, H
The American journal of cardiology. 2020;(7):1102-1107
Abstract
Atrial fibrillation (AF) is a common co-morbidity in patients undergoing transcatheter aortic valve implantation (TAVI), but whether direct oral anticoagulants (DOACs) confer similar safety and efficacy compared with vitamin K antagonist (VKA) remains unclear in this population. The aim of our study was to investigate the safety and efficacy of DOACs compared with VKA in patients undergoing TAVI with concomitant indication of oral anticoagulation. PUBMED and EMBASE were searched through October 2019 for studies comparing DOACs versus VKA in patients undergoing TAVI with indication of oral anticoagulation. The main efficacy outcomes were all-cause mortality and stroke whereas the main safety outcome was major and/or life-threatening bleeding. Our search identified 5 eligible studies including 2,569 patients. Majority of patients had atrial fibrillation as indication of anticoagulation. There were no significant differences in all-cause mortality, major and/or life-threatening bleeding, and stroke in patients treated with DOACs versus VKA (odds ratio [OR] 1.07, 95% confidence interval [CI] [0.73 to 1.57], p = 0.72, OR = 0.85, 95% CI [0.64 to 1.12], p = 0.24, OR 1.52, 95% CI [0.93 to 2.48], p = 0.09, respectively). In conclusion, in patients undergoing TAVI with concomitant indication for oral anticoagulation, all-cause mortality, major and/or life-threatening bleeding, and stroke were similar between DOACs and VKA. Further large scale randomized controlled trials are needed to search the optimal oral anticoagulation regimen in this population.
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9.
Evolving Approaches to Antithrombotics in Stroke Prevention and Treatment.
Javalkar, V, Kuybu, O, Amireh, A, Kelley, RE
Southern medical journal. 2020;(11):585-592
Abstract
The optimization of antithrombotic therapy for acute stroke treatment and secondary prevention is an evolving process based on an increasing array of studies that provide an evidence-based approach. Options have increased dramatically with the release of the non-vitamin K oral anticoagulants and with the results of recent randomized clinical trials designed to assess potential benefits versus risks for patients in an individualized fashion. Recent studies have provided important information to guide choice and dosing of antiplatelet agents as well as the length of treatment. Anticoagulant use is particularly pertinent for stroke prevention in patients at higher risk of atrial fibrillation and may have a place in certain other stroke mechanisms. One important focus of study is the potential benefit of combined antiplatelet and anticoagulant therapy. Options for our patients, when the initial choice of therapy does not demonstrate benefit or is not well tolerated, clearly, are valuable. For example, short-term dual antiplatelet therapy for minor stroke and transient ischemic attack is being adopted, but with the recognition that longer-term combined therapy is not worth the increased risk of bleeding. Alternative antiplatelet choices, such as cilostazol and possibly ticagrelor, may be of benefit for refractory patients and this could affect the decision-making process. This review represents an effort to incorporate the information from more recent stroke prevention and treatment studies with information gleaned from prior studies.
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10.
Management of anticoagulant-refractory thrombotic antiphospholipid syndrome.
Cohen, H, Sayar, Z, Efthymiou, M, Gaspar, P, Richards, T, Isenberg, D
The Lancet. Haematology. 2020;(8):e613-e623
Abstract
Lifelong anticoagulation with warfarin or alternative vitamin K antagonist is the standard anticoagulant treatment for thrombotic antiphospholipid syndrome. Anticoagulant-refractory thrombotic antiphospholipid syndrome can be broadly defined as breakthrough thrombosis while on standard oral anticoagulation treatment and its management is a major challenge given the serious nature of the thrombotic disease observed, which has become refractory to oral anticoagulation. The factors (genetic and cellular) that cause anticoagulant-refractory thrombotic antiphospholipid syndrome are now better understood. However, efforts to use this greater understanding have not yet transformed the capacity to treat it successfully in many patients. In this Viewpoint, we review the factors that are likely to be contributing to the cause of this syndrome and consider how they might be modified or inhibited. We also discuss management, including general strategies to minimise thrombotic risk, intensification of anticoagulation, addition of an antiplatelet agent, adjunctive treatment for thrombosis, immunomodulatory therapy, complement inhibition, vascular options, and future potential therapeutic targets.