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1.
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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2.
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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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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4.
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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5.
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.
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6.
Medical Management for Secondary Stroke Prevention.
Kim, AS
Continuum (Minneapolis, Minn.). 2020;(2):435-456
Abstract
PURPOSE OF REVIEW This article reviews the evidence base and recommendations for medical management for secondary stroke prevention. RECENT FINDINGS Recent developments for secondary stroke prevention include evidence to support the use of short-term dual antiplatelet therapy after minor stroke and transient ischemic attack, direct oral anticoagulants for nonvalvular atrial fibrillation, reversal agents for direct oral anticoagulant-associated hemorrhage, and aspirin rather than presumptive anticoagulation with a direct oral anticoagulant for embolic stroke of undetermined source. SUMMARY Most strokes are preventable. The mainstays of medical management for secondary stroke prevention include antihypertensive therapy; antithrombotic therapy, with antiplatelet agents for most stroke subtypes or anticoagulants such as warfarin or a direct oral anticoagulant for cardioembolic stroke specifically; cholesterol-lowering therapy, principally with statins, but with potential roles for ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors in selected patients; and glycemic control to prevent microvascular complications from diabetes mellitus or pioglitazone in selected patients with insulin resistance but not diabetes mellitus.
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7.
Tackling Elevated Risk in PAD: Focus on Antithrombotic and Lipid Therapy for PAD.
Govsyeyev, N, Nehler, MR, Hiatt, WR, Bonaca, MP
Current cardiology reports. 2020;(3):13
Abstract
The PAD population is at increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Risk factor modification, symptom control, antithrombotic, and lipid therapies are the mainstays of PAD medical therapy. Recent data has challenged prior recommendations regarding the optimal secondary prevention strategies in PAD. PURPOSE OF REVIEW To review clinical evidence from large randomized controlled trials showing the benefit of antithrombotic and lipid therapy in the PAD population. RECENT FINDINGS The COMPASS trial challenged prior recommendations regarding anticoagulation in PAD. Among the PAD subgroup, rivaroxaban 2.5 mg plus aspirin reduced MACE (HR 0.72, 95% CI 0.57-0.90, p = 0.0047), MALE (HR 0.54, 95% CI 0.35-0.82, p = 0.0037), and major amputation (HR 0.30, 95% CI 0.11-0.80, p = 0.011) compared with aspirin monotherapy. The THEMIS trial showed a 55% risk reduction for MALE with ticagrelor DAPT compared with aspirin monotherapy (HR 0.45, 95% CI 0.23-0.86). The FOURIER trial revealed that lowering LDL cholesterol below current targets with a PCSK9 inhibitor reduced MACE (HR 0.73, 95% CI 0.59-0.91, p = 0.0040) and MALE (HR 0.43, 95% CI 0.19-0.99, p = 0.042) in subjects with symptomatic PAD. Recent high-quality evidence shows the benefit of antiplatelet therapy, anticoagulation therapy, and lipid therapy in reducing MACE and MALE in PAD. Despite these findings, implementation remains a challenge and focus should now shift towards adopting evidence-based recommendations in clinical practice.
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8.
Benefit-Risk Tradeoffs in Assessment of New Drugs and Devices.
Kaul, S, Stockbridge, N, Butler, J
Circulation. 2020;(20):1974-1988
Abstract
Balancing benefits and risks is a complex task that poses a major challenge, both to the approval of new medicines and devices by regulatory authorities and in therapeutic decision-making in practice. Several analysis methods and visualization tools have been developed to help evaluate and communicate whether the benefit-risk profile is favorable or unfavorable. In this White Paper, we describe approaches to benefit-risk assessment using qualitative approaches such as the Benefit Risk Action Team framework developed by the Pharmaceutical Research and Manufacturers of America, and the Benefit-Risk Framework developed by the United States Food and Drug Administration; and quantitative approaches such as the numbers needed to treat for benefit and harm, the benefit-risk ratio, and Incremental Net Benefit. We give illustrative examples of benefit-risk evaluations using 4 treatment interventions including sodium glucose cotransporter 2 inhibitors in patients with type 2 diabetes; a direct antithrombin agent, dabigatran, for reducing stroke and systemic embolism in patients with nonvalvular atrial fibrillation; transcatheter aortic valve replacement in patients with symptomatic severe aortic valve stenosis; and antiplatelet agents vorapaxar and prasugrel for reducing cardiovascular events in patients at high cardiovascular risk. Regular applications of structured benefit-risk assessment, whether qualitative, quantitative, or both, enabled by easy-to-understand graphical presentations that capture uncertainties around the benefit-risk metric, may aid shared decision-making and enhance transparency of those decisions.
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9.
A critical evaluation of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura.
Gómez-Seguí, I, Fernández-Zarzoso, M, de la Rubia, J
Expert review of hematology. 2020;(11):1153-1164
Abstract
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy caused by inhibitory autoantibodies against ADAMTS13 protein. Until recently, the combination of plasma exchange (PEX) and immunosuppression has been the standard front-line treatment in this disorder. However, aTTP-related mortality, refractoriness, and relapse are still a matter of concern. Areas covered: The better understanding of the pathophysiological mechanisms of aTTP has allowed substantial improvements in the diagnosis and treatment of this disease. Recently, the novel anti-VWF nanobody caplacizumab has been approved for acute episodes of aTTP. Caplacizumab is capable to block the adhesion of platelets to VWF, therefore inhibiting microthrombi formation in the ADAMTS13-deficient circulation. In this review, the characteristics of caplacizumab together with the available data of its efficacy and safety in the clinical setting will be analyzed. Besides, the current scenario of aTTP treatment will be provided, including the role of other innovative drugs. Expert opinion: With no doubt, caplacizumab is going to change the way we treat aTTP. In combination with standard treatment, caplacizumab can help to significantly reduce aTTP-related mortality and morbidity and could spare potential long-term consequences by minimizing the risk of exacerbation.
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10.
Meta-Analysis of Antithrombotic Strategies in Patients With Heart Failure With Reduced Ejection Fraction and Sinus Rhythm.
Ueyama, H, Takagi, H, Briasoulis, A, Harrington, M, Steinberg, D, Kuno, T
The American journal of cardiology. 2020;:92-98
Abstract
Heart failure with reduced ejection fraction (HFrEF) is associated with an increased risk of thrombotic events. We compared the safety and efficacy of different antithrombotic strategies for HFrEF and sinus rhythm. PubMed and Embase were searched through January 2020 for studies comparing oral anticoagulants versus antiplatelet agents or placebo in HFrEF and sinus rhythm to include in this network meta-analysis. We identified 5 randomized controlled trials with a total of 9,390 patients randomized to low dose rivaroxaban, vitamin K antagonist (VKA), antiplatelets, or placebo. Low dose rivaroxaban and VKA did not show a significant decrease in stroke compared with placebo but were associated with an increased risk of major bleeding (risk ratio [RR] 6.86, 95% confidence interval [CI] 1.16 to 40.7; RR 8.62, 95% CI 1.52 to 48.9, respectively). When compared with antiplatelets, low dose rivaroxaban and VKA were associated with a significantly decreased risk of stroke (RR 0.67, 95% CI 0.47 to 0.96; RR 0.50, 95% CI 0.33 to 0.76, respectively), but with a significantly increased risk of major bleeding (RR 1.65, 95% CI 1.16 to 2.33; RR 2.07, 95% CI 1.51 to 2.84, respectively). There was no significant difference in these outcomes between low dose rivaroxaban versus VKA and antiplatelets versus placebo. There were no significant differences in all-cause mortality, myocardial infarction, or rehospitalization for heart failure among each treatment. In conclusion, in patient with HFrEF and sinus rhythm, use of oral anticoagulation with or without antiplatelet agents increases the risk of bleeding without substantial effects on the risk of ischemic stroke.