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Background:  Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved., Aims:  We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial., Patients and Methods:  A total of 3,874 patients were included in the primary analysis (day 31-180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding., Results:  The rates of recurrent VTE and bleeding events were higher in patients with a TTR below the median (< 66% vs. ≥66%) resulting in an absolute risk difference (ARD) of +0.5% (95% confidence interval: 0%, +1.1%) and +2.2% (0.9%, +3.5%), respectively. Patients with high SAMe-TT2-R2 score were 76% of total and had lower median TTR (64.7% vs. 70.7%). The SAMe-TT2-R2 score exhibited low negative (0.59) and positive (0.52) predictive value (TTR threshold 66%), and poor discrimination (c-statistic, 0.58). ARD between patients with high and low score was 0% (-0.6%, +0.7%) for recurrence and +1.3% (-0.1%, +2.7%) for bleeding. Results were confirmed in sensitivity analyses focusing on the whole study period (day 1-365)., Conclusion:  In VTE patients, the SAMe-TT2-R2 score showed unsatisfactory discrimination and predictive value for individual TTR and did not correlate well with clinical outcomes. The choice of starting a patient on VKA cannot be based on this parameter and its routine use after VTE may not translate into clinical usefulness., Competing Interests: Stefano Barco has received congress and travel payments from Bayer HealthCare and Daiichi-Sankyo, lecture honoraria from BTG Interventional Medicine and financial support for the printing costs of his PhD thesis from Pfizer BV, CSL Behring bv, Sanquin Plasma Products, Boehringer Ingelheim bv, Aspen Netherlands and Bayer bv. Serena Granziera has received congress and travel payments from Daiichi-Sankyo, Bayer and Boehringer Ingelheim. Michiel Coppens reports grants from Boehringer Ingelheim, grants, personal fees, non-financial support and other from Bayer, grants, personal fees, non-financial support and other from Daiichi Sankyo, other from Pfizer, personal fees from Bristol Myers Squibb, other from Portola, personal fees and non-financial support from CSL Behring, personal fees from Aspen Pharma Group. J. Douxfils is CEO and founder of QUALIblood s.a. and reports personal fees from Stago and Daiichi-Sankyo. Mathilde Nijkeuter and Nicoletta Riva have no relevant disclosures. Thomas Vanassche has received speaker's fee and/or participated in advisory boards from Boehringer Ingelheim, Pfizer, Daiichi Sankyo and Bayer. George Zhang and Min Lin are employees of Daiichi-Sankyo Inc. Pieter W. Kamphuisen has received honoraria from LEO Pharma. Alexander Cohen reports grants and personal fees from BristolMyers Squibb and Pfizer Limited and personal fees from Boehringer Ingelheim, Johnson & Johnson, Portola, Sanofi Aventis, XO1, Janssen, Bayer HealthCare and grants from Daiichi Sankyo. Jan Beyer-Westendorf reports grants and personal fees from Bayer AG, Boehringer-Ingelheim, Daiichi Sankyo, Pfizer and Portola, (Georg Thieme Verlag KG Stuttgart · New York.)

In the past 2 decades, the direct oral anticoagulants (DOACs) have emerged as alternatives to the standard therapy (unfractionated or low-molecular-weight heparin followed by vitamin K antagonists [VKA]), for the acute and extended treatment of venous thromboembolism. The DOACs have a more favorable pharmacologic profile and a predictable anticoagulant response and, therefore, have the potential to overcome some of the limitations associated with the use of VKA. Several ongoing registries are evaluating the use of the DOACs in routine clinical practice and will provide additional information in less selected patient populations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Anticoagulant treatment can be currently instituted with two different classes of drugs: the vitamin K antagonists (VKAs) and the newer, "novel" or non-vitamin K antagonist oral anticoagulant drugs (NOACs). The NOACs have several practical advantages over VKAs, such as the rapid onset/offset of action, the lower potential for food and drug interactions, and the predictable anticoagulant response. However, the VKAs currently have a broader spectrum of indications, a standardized monitoring test, and established reversal strategies. The NOACs emerged as alternative options for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Nevertheless, there remain some populations for whom the VKAs remain the most appropriate anticoagulant drug. This article discusses the advantages and disadvantages of VKAs and NOACs., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Treatment of splanchnic vein thrombosis (SVT) is a clinical challenge due to heterogeneity of clinical presentations, increased bleeding risk, and lack of evidences from clinical trials. We performed an international registry to describe current treatment strategies and factors associated with therapeutic decisions in a large prospective cohort of unselected SVT patients. A total of 613 patients were enrolled (mean age 53.1 years, standard deviation ± 14.8); 62.6% males; the majority (468 patients) had portal vein thrombosis. Most common risk factors included cirrhosis (27.8%), solid cancer (22.3%), and intra-abdominal inflammation/infection (11.7%); in 27.4% of patients, SVT was idiopathic. During the acute phase, 470 (76.7%) patients received anticoagulant drugs, 136 patients (22.2%) remained untreated. Incidental diagnosis, single vein thrombosis, gastrointestinal bleeding, thrombocytopenia, cancer, and cirrhosis were significantly associated with no anticoagulant treatment. Decision to start patients on vitamin K antagonists after an initial course of parenteral anticoagulation was significantly associated with younger age, symptomatic onset, multiple veins involvement, and unprovoked thrombosis. Although a nonnegligible proportion of SVT patients did not receive anticoagulant treatment, the majority received the same therapies recommended for patients with usual sites thrombosis, with some differences driven by the site of thrombosis and the pathogenesis of the disease., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100’pt-y) and in patients with permanent risk factors (10.2/100’pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups. [ABSTRACT FROM AUTHOR]

Background--Novel oral anticoagulants (NOACs) have been proposed as alternatives to vitamin K antagonists for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Individually, NOACs were at least noninferior to vitamin K antagonists, but a clear superiority in overall and vascular mortality was not consistently proven. Methods and Results--We performed a meta-analysis of phase II and phase III randomized, controlled trials comparing NOACs with vitamin K antagonists in patients with atrial fibrillation. The MEDLINE and EMBASE databases, supplemented with conference abstract books and www.clinicaltrials.gov, were searched up to the first week of July 2012 with no language restriction. Two reviewers performed independent article review and study quality assessment. Data on overall and cardiovascular mortality, stroke or systemic embolism, ischemic stroke, major and intracranial bleeding, and myocardial infarction were collected. NOACs were pooled to perform a comparison with vitamin K antagonists, calculating pooled relative risks (RRs) and associated 95% confidence intervals (CIs). We retrieved 12 studies (3 administering dabigatran, 4 administering rivaroxaban, 2 administering apixaban, and 3 administering edoxaban) enrolling a total of 54 875 patients. NOACs significantly reduced total mortality (5.61% versus 6.02%; RR, 0.89; 95% CI, 0.83-0.96), cardiovascular mortality (3.45% versus 3.65%; RR, 0.89; 95% CI, 0.82-0.98), and stroke/systemic embolism (2.40% versus 3.13%; RR, 0.77; 95% CI, 0.70-0.86). There was a trend toward reduced major bleeding (RR, 0.86; 95% CI, 0.72-1.02) with a significant reduction of intracranial hemorrhage (RR, 0.46; 95% CI, 0.39-0.56). No difference in myocardial infarction was observed. Conclusions--NOACs are associated with an overall clinical benefit compared with vitamin K antagonists. Additional research is required to confirm these findings outside the context of randomized trials. [ABSTRACT FROM AUTHOR]

Objective: Subtherapeutic international normalized ratios are frequently encountered in clinical practice, and patients with mechanical heart valves with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events. There are no data on thromboembolic event risk for these patients. Methods: We assessed the current practice patterns in the management of patients with mechanical heart valves with subtherapeutic international normalized ratios and assessed the risk of thromboembolic complications in this setting. The charts of patients with mechanical heart valves followed up in two anticoagulation clinics were reviewed. Patients with a history of stable, therapeutic anticoagulation but with a subtherapeutic international normalized ratio were included. Patients who underwent invasive procedures requiring temporary suspension of antithrombotic therapy were excluded. Data on use and dose of low–molecular weight heparin bridging therapy were collected. Results: The incidence of objectively confirmed thromboembolic events within 90 days after obtaining the index international normalized ratio was assessed. Two hundred ninety-four patients with mechanical heart valves were included (mean age 63.3 years, 47.3% male). Low–molecular weight heparin was prescribed in 14 cases (4.8%). At 90 days, 1 patient had a thromboembolic complication (0.3%, 95% confidence interval 0%–1.9%). Conclusion: Patients with previously stable, therapeutic anticoagulation with a subtherapeutic international normalized ratio have a low risk of thromboembolic events. Withholding low–molecular weight heparin bridging therapy is a reasonable therapeutic option in these cases. [Copyright &y& Elsevier]