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Use of oral anticoagulants in patients with atrial fibrillation and renal dysfunction.
Potpara, TS, Ferro, CJ, Lip, GYH
Nature reviews. Nephrology. 2018;(5):337-351
Abstract
Atrial fibrillation (AF) and chronic kidney disease (CKD) are increasingly prevalent in the general population and share common risk factors such as older age, hypertension and diabetes mellitus. The presence of CKD increases the risk of incident AF, and, likewise, AF increases the risk of CKD development and/or progression. Both conditions are associated with substantial thromboembolic risk, but patients with advanced CKD also exhibit a paradoxical increase in bleeding risk. In the landmark randomized clinical trials that compared non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin for thromboprophylaxis in patients with AF, the efficacy and safety of NOACs in patients with mild-to-moderate CKD were similar to those in patients without CKD. Dose adjustment of NOACs as per the prescribing label is required in this population. Owing to limited trial data, evidence-based recommendations for the management of patients with AF and severe CKD or end-stage renal disease on dialysis are lacking. Observational cohort studies have reported conflicting results, and the management of these particularly vulnerable patients remains challenging and requires careful assessment of stroke and bleeding risk and, where appropriate, use of warfarin with good-quality anticoagulation control.
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The critical interaction between valproate sodium and warfarin: case report and review.
Zhou, C, Sui, Y, Zhao, W, Dong, C, Ren, L, Song, P, Xu, B, Sun, X
BMC pharmacology & toxicology. 2018;(1):60
Abstract
BACKGROUND Valproic acid (VPA) and warfarin are commonly prescribed for patients with epilepsy and concomitant atrial fibrillation (AF). When VPA and warfarin are prescribed together, clinically important interactions may occur. VPA may replace warfarin from the protein binding sites and result in an abnormally increased anticoagulation effect. This is commonly underrecognized. CASE PRESENTATION In our case, we report a 78-year-old woman with a glioma who presented with status epilepticus. The patient was on warfarin to prevent cardiogenic embolism secondary to AF. Intravenous loading dose of VPA was administered, but international normalized ratio (INR) increased significantly to 8.26. Intravenous vitamin K1 was then given and the patient developed no overt bleeding during the hospitalization. CONCLUSION By reviewing the literature and discussing the critical interaction between valproate sodium and warfarin, we conclude that intravenous VPA and the co-administrated warfarin may develop critical but underrecognized complications due to effects on the function of hepatic enzymes and displacement of protein binding sites.
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3.
Management of Perioperative Anticoagulation for Device Implantation.
Stewart, MH, Morin, DP
Cardiac electrophysiology clinics. 2018;(1):99-109
Abstract
Periprocedural management of anticoagulation for cardiac device implantation has evolved over the past 20 years. The traditional paradigm of vitamin K antagonist interruption with heparin bridging has now been shown to be less safe than continuation of vitamin K antagonists at therapeutic levels. Dual antiplatelet therapy during device implantation poses substantial risk but is often necessary. The safest dosing strategy for newer direct oral anticoagulants is still not clear.
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Management of bleeding in patients receiving non-vitamin K antagonists.
Balla, S, Koerber, S, Flaker, G
Postgraduate medical journal. 2017;(1098):221-225
Abstract
Anticoagulation with non-vitamin K antagonists (Non vitamin K oral anticoagulant (NOACs)) including dabigatran, rivaroxaban, apixaban and edoxaban is at least as effective as warfarin, has fewer drug and food interactions and does not require monthly monitoring. Although major bleeding with NOACs is infrequent, there remains concern about the ability to effectively treat episodes of major bleeding. New agents have been developed that are capable of providing rapid reversal of the anticoagulation effect of NOACs. Idarucizumab normalises the dilute thrombin time and the ecarin clotting time, both of which are elevated with dabigatran. Andexanet alfa reduces increased anti-factor Xa activity seen with the use of rivaroxaban and apixaban. A universal reversal agent is in development. These agents, unlike agents to reverse the anticoagulation effect of vitamin K antagonists, appear to reverse the specific NOAC anticoagulant. The development of reversal agents is a major advancement in managing bleeding in the era of NOACs. Future studies will be required to determine the impact on important clinical outcomes.
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5.
Vitamin K antagonists for stroke prevention in hemodialysis patients with atrial fibrillation: A systematic review and meta-analysis.
Van Der Meersch, H, De Bacquer, D, De Vriese, AS
American heart journal. 2017;:37-46
Abstract
BACKGROUND The use of vitamin K antagonists (VKAs) in hemodialysis patients with atrial fibrillation (AF) is controversial. No randomized trials are available and observational studies have yielded conflicting results, engendering a large clinical practice variability and physician uncertainty. An unresolved but highly relevant question is whether AF poses a true risk of ischemic stroke in hemodialysis and whether any form of oral anticoagulation is therefore warranted. METHODS We conducted a systematic review of studies that compared the incidence of ischemic stroke and bleeding in hemodialysis patients with AF taking VKA and those not taking VKA. When hemodialysis patients had been pooled with peritoneal dialysis, kidney transplant, or stage V chronic kidney disease patients, unpublished outcome data of the hemodialysis subgroup were obtained through personal communication. The main outcome measures were ischemic stroke/thromboembolic events, all-cause mortality, major bleeding, and hemorrhagic stroke. Combined hazard ratios (HRs) and 95% CIs were calculated using a random-effects model. RESULTS Twelve prospective or retrospective cohort studies were included in the meta-analysis, totaling 17,380 hemodialysis patients of whom 4,010 (23.1%) received VKA. In VKA-treated patients, mean CHADS2 or CHA2DS2VASc score was low (range 1.7-2.75) or a sizeable proportion of patients had scores <2 (range 2%-23%). Time in the therapeutic range or mean international normalized ratio was generally low. Treatment with VKA was associated with a nonsignificant 26% reduction of the risk of ischemic stroke (HR 0.74; 0.51-1.06), a 21% increase in total bleeding risk (HR 1.21; 1.03-1.43), and no effect on mortality (HR 1.00; 0.92-1.09). Vitamin K antagonist almost doubled the risk of hemorrhagic stroke, but this did not reach the limit of statistical significance (4 studies, n = 16.365; HR 1.93; 0.93-3.98). CONCLUSION Our meta-analysis revealed a trend for a reduction of the risk of ischemic stroke in hemodialysis patients with AF treated with VKA. The true protective effect may have been underestimated, owing to inclusion of low-risk patients not expected to benefit from anticoagulation and to suboptimal anticoagulation. However, assessment of the overall effect of VKA in hemodialysis patients should also take into account the increased risk of bleeding, in particular of hemorrhagic stroke. Whether new oral anticoagulants provide a better benefit-risk ratio in hemodialysis patients should be the subject of future trials.
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6.
Warfarin-Associated Nonuremic Calciphylaxis.
Yu, WY, Bhutani, T, Kornik, R, Pincus, LB, Mauro, T, Rosenblum, MD, Fox, LP
JAMA dermatology. 2017;(3):309-314
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Abstract
IMPORTANCE Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis. OBJECTIVE To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis. DESIGN, SETTING, AND PARTICIPANTS We searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms "calciphylaxis and warfarin," "non-uremic calciphylaxis," and "nonuremic calciphylaxis." We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate <15 mL/min; acute kidney injury requiring dialysis; and renal transplantation). EXPOSURES Each patient had been exposed to warfarin before the onset of calciphylaxis. MAIN OUTCOMES AND MEASURES Patient data were abstracted from published reports. Original patient medical records were requested and reviewed when possible. RESULTS We identified 18 patients with nonuremic calciphylaxis, 15 from the literature, and 3 from our institution. Patients were predominantly female (15 of 18 [83%]) with ages ranging from 19 to 86 years. Duration of warfarin therapy prior to calciphylaxis onset averaged 32 months. Lesions were usually located below the knees (in 12 of 18 [67%]). No cases reported elevated calcium-phosphate products (0 of 17 [0%]). Calcifications were most often noted in the tunica media (n = 8 [44%]) or in the vessel lumen and tunica intima (n = 7 [39%]). The most common treatments included substitution of heparin or low-molecular weight heparin for warfarin (n = 13 [72%]), intravenous sodium thiosulfate (n = 9 [50%]), and hyperbaric oxygen (n = 3 [17%]). The survival rate on hospital discharge was remarkably high, with 15 cases (83%) reporting full recovery and 3 cases ending in death. CONCLUSIONS AND RELEVANCE Warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course, and, particularly, outcome. This finding should influence clinical management of the disease and informs targeted treatment of the disease.
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Noncentral Nervous System Systemic Embolism in Patients With Atrial Fibrillation: Results From ROCKET AF (Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).
Orgel, R, Wojdyla, D, Huberman, D, Halperin, JL, Breithardt, G, Singer, DE, Fox, KAA, Hankey, GJ, Mahaffey, KW, Jones, WS, et al
Circulation. Cardiovascular quality and outcomes. 2017;(5)
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Oral anticoagulant therapy for older patients with atrial fibrillation: a review of current evidence.
Bo, M, Grisoglio, E, Brunetti, E, Falcone, Y, Marchionni, N
European journal of internal medicine. 2017;:18-27
Abstract
Atrial fibrillation is more frequent in older patients, who have a higher risk of cardioembolic stroke and thromboembolism. Oral anticoagulant therapy is the standard of treatment for stroke prevention; however, under-prescription is still very common in older patients. The reasons underlying this phenomenon have not been systematically investigated, and true contraindications only partially account for it. An intimate skepticism on the real benefit-risk balance of oral anticoagulant therapy in the oldest patients seems to derive from the fact that most studies supporting it were conducted decades ago and included younger patients, with overall better functional and clinical status. In this review we will focus on the main barriers to anticoagulant therapy prescription in older patients and summarize the available evidences on the efficacy and safety of vitamin K antagonists and direct oral anticoagulants in this population. The encouraging evidence of a higher net clinical benefit of direct oral anticoagulants compared with warfarin should hopefully widen the treatment options also for frail individuals, thereby allowing a greater number of patients to be treated according to current international guidelines.
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The SAMe-TT2R2 score and decision-making between a vitamin K antagonist or a non-vitamin K antagonist oral anticoagulant in patients with atrial fibrillation.
Esteve-Pastor, MA, Roldán, V, Valdés, M, Lip, GY, Marín, F
Expert review of cardiovascular therapy. 2016;(2):177-87
Abstract
Oral anticoagulation therapy is essential in patients with atrial fibrillation and clinicians need guidance on decision-making between the vitamin K antagonists (VKA), e.g. warfarin, or non-vitamin K antagonist oral anticoagulants. Observational studies have shown that patients who receive VKA therapy spend a significant percentage of their time with international normalized ratio values outside of the therapeutic range (time in therapeutic range, TTR <60%.) Recently, a clinical score has been developed with commonly encountered clinical features, the SAMe-TT2R2 score, to help decision-making with regard to whether a patient is likely to do well, or not, with a VKA. Those with a SAMe-TT2R2 score of 0-1 are likely to do well on a VKA, while those with a SAMe-TT2R2 score ≥ 2 are on probability going to achieve suboptimal TTR. In this article, we provide an overview of the main published retrospective and prospective studies that have validated the SAMe-TT2R2 score and its value for decision-making in daily clinical practice.
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10.
Stroke Prevention in Atrial Fibrillation: Focus on Latin America.
Massaro, AR, Lip, GYH
Arquivos brasileiros de cardiologia. 2016;(6):576-589
Abstract
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with an estimated prevalence of 1-2% in North America and Europe. The increased prevalence of AF in Latin America is associated with an ageing general population, along with poor control of key risk factors, including hypertension. As a result, stroke prevalence and associated mortality have increased dramatically in the region. Therefore, the need for effective anticoagulation strategies in Latin America is clear. The aim of this review is to provide a contemporary overview of anticoagulants for stroke prevention. The use of vitamin K antagonists (VKAs, eg, warfarin) and aspirin in the prevention of stroke in patients with AF in Latin America remains common, although around one fifth of all AF patients receive no anticoagulation. Warfarin use is complicated by a lack of access to effective monitoring services coupled with an unpredictable pharmacokinetic profile. The overuse of aspirin is associated with significant bleeding risks and reduced efficacy for stroke prevention in this patient group. The non-VKA oral anticoagulants (NOACbs) represent a potential means of overcoming many limitations associated with VKA and aspirin use, including a reduction in the need for monitoring and a reduced risk of hemorrhagic events. The ultimate decision of which anticoagulant drug to utilize in AF patients depends on a multitude of factors. More research is needed to appreciate the impact of these factors in the Latin American population and thereby reduce the burden of AF-associated stroke in this region.