scholarly journals INR Stability, Clinical Importance, and Predictors in Patients With Atrial Fibrillation and Venous Thromboembolism Receiving Vitamin K Antagonists

2016 ◽  
Vol 32 (6) ◽  
pp. 253-259
Author(s):  
C. Michael White
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Vitamin K ◽  
Systematic Reviews ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Bleeding Event ◽  
The United States ◽  
Bleeding Complications ◽  
Anticoagulation Clinics

Objective: Compare and contrast systematic reviews/meta-analyses assessing the time in the therapeutic range (TTR) for vitamin K antagonists (VKAs), clinical impact, and predictors. Data Sources: OVID MEDLINE search (1980-June 1, 2016) using the terms “vitamin K antagonist or warfarin” and “systematic review or meta-analysis” with backwards citation tracking from procured articles. Study Selection and Data Extraction: Search results were limited to systematic reviews assessing TTR with VKAs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). Data Synthesis: Six systematic reviews assessed TTR (4 in AF, 2 in VTE), and 3 of those assessed control at the time of a thrombotic or bleeding event (2 in AF, 1 in VTE). In patients on VKAs, greater TTR is correlated with fewer thromboembolic events and bleeding complications. VKA naïve patients have a harder time maintaining TTR than those with a previous knowledge of the likely therapeutic dose. Patients in the United States spend less TTR than those in other countries. Randomized clinical trials and anticoagulation clinics achieve greater TTR than those treated outside of these settings. The overall TTR has not improved from the first systematic reviews to the newest ones even though they were conducted 10 years apart and contained many new studies. Also, TTR in AF and VTE is similar. Conclusions: TTR is an important metric of VKA efficacy and safety and needs to be optimized. Many factors such as being VKA naïve can compromise TTR, and the use of anticoagulation clinics to optimize therapy is an important approach.

Incidence of Recurrent Thromboembolic and Bleeding Complications Among Patients With Venous Thromboembolism in Relation to Both Malignancy and Achieved International Normalized Ratio: A Retrospective Analysis

2000 ◽  
Vol 18 (17) ◽  
pp. 3078-3083 ◽  
Author(s):  
Barbara A. Hutten ◽  
Martin H. Prins ◽  
Michael Gent ◽  
Jeff Ginsberg ◽  
Jan G. P. Tijssen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Retrospective Analysis ◽  
Vitamin K ◽  
Major Bleeding ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Bleeding Complications ◽  
Venous Thromboembolic

PURPOSE: Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR.PATIENTS AND METHODS: In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0.RESULTS: In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0.CONCLUSION: Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy.

scholarly journals Optimal Anticoagulation Strategy for Cardioversion in Atrial Fibrillation

2015 ◽  
Vol 4 (1) ◽  
pp. 44 ◽  
Author(s):  
Philipp Bushoven ◽  
Sven Linzbach ◽  
Mate Vamos ◽  
Stefan H Hohnloser ◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Prospective Trial ◽  
Bleeding Complications ◽  
Order Of Magnitude ◽  
Pharmacological Cardioversion

For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion.

HEMATURIA AND OTHER KINDS OF BLEEDINGS ON NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN UPDATED OVERVIEW ON OCCURRENCE, PATHOMECHANISMS AND MANAGEMENT

2020 ◽  
Vol 73 (11) ◽  
pp. 2528-2534
Author(s):  
Dagmara Wojtowicz ◽  
Anna Tomaszuk-Kazberuk ◽  
Jolanta Małyszko ◽  
Marek Koziński
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Anticoagulant Activity ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Bleeding Complications ◽  
Reversal Agents ◽  
Limited Availability ◽  
Increased Risk

Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended for oral anticoagulation in patients with non-valvular atrial fibrillation. In the setting, NOACs effectively prevent from stroke and systemic embolic events. In spite of the favorable safety profile of NOACs when compared with vitamin K antagonists, the use of any kind of anticoagulation is associated with an increased risk of bleeding. However, there is still a lack of direct comparisons of effectiveness and safety among NOACs. The results of indirect comparisons and meta-analyses suggest that the risk of various types of hemorrhagic complications differ among the particular NOACs. Management of bleeding in patients under NOAC therapy can be challenging because of limited availability of antidotes and the lack of routine laboratory test monitoring the NOAC anticoagulant effect. In case of life-threatening or critical site bleeding, reversal of NOAC anticoagulant activity is essential together with immediate implementation of causative treatment. Moreover, some patients on chronic NOAC therapy may require urgent surgery or invasive procedures. Specific reversal agents for NOACs have been developed, i.e. more widely available idarucizumab for the factor IIa inhibitor (dabigatran) and andexanet alfa for the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with limited availability. This review summarizes the occurrence and management of NOAC-related bleeding complications with a particular emphasis on hematuria.

The NOACs: clinical pharmacology

ESC CardioMed ◽  
2018 ◽  
pp. 268-272
Author(s):  
Jeffrey Weitz
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Active Site ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
High Affinity

The limitations of vitamin K antagonists prompted the development of new oral anticoagulants that could be administered in fixed doses without routine coagulation monitoring. Focusing on thrombin and factor Xa because of their prominent roles in coagulation, structure-based design led to the development of small molecules that bind to the active site pockets of these enzymes with high affinity and specificity. Four non-vitamin K antagonist oral anticoagulants are now licensed: dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In phase III randomized clinical trials that included over 100,000 patients these agents have proven to be at least as effective as vitamin K antagonists for prevention of stroke in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less bleeding, particularly less intracranial bleeding.

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

2020 ◽  
Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Efficacy And Safety

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

Long-term quality of VKA treatment and clinical outcome after extreme overanticoagulation in 14,777 AF and VTE patients

2015 ◽  
Vol 113 (04) ◽  
pp. 881-890 ◽  
Author(s):  
Nic J. G. M. Veeger ◽  
Nakisa Khorsand ◽  
Hanneke C. Kluin-Nelemans ◽  
Hilde A. M. Kooistra ◽  
Karina Meijer ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Clinical Outcome ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
P Value ◽  
Risk Of Bleeding ◽  
Increased Risk

SummaryVitamin K antagonists (VKA) are widely used in atrial fibrillation and venous thromboembolism (VTE). Their efficacy and safety depend on individual time in the therapeutic range (iTTR). Due to the variable dose-response relationship within patients, also patients with initially stable VKA treatment may develop extreme overanticoagulation (EO). EO is associated with an immediate bleeding risk, but it is unknown whether VKA treatment will subsequently restabilise. We evaluated long-term quality of VKA treatment and clinical outcome after EO. EO was defined as international normalized ratio (INR) ≥ 8.0 and/or unscheduled vitamin K supplementation. We included a consecutive cohort of initially stable atrial fibrillation and venous thromboembolism patients. In EO patients, the 90 days pre- and post-period were compared. In addition, patients with EO were compared with patients without EO using a matched 1:2 cohort. Of 14,777 initially stable patients, 800 patients developed EO. The pre-period was characterised by frequent overanticoagulation, and half of EO patients had an inadequate iTTR (< 65 %). After EO, underanticoagulation became more prevalent. Although the mean time between INR-measurements decreased from 18.6 to 13.2 days, after EO inadequate iTTR became more frequent (62 %), p-value < 0.001. A 2.3 times (95 % confidence interval [CI] 2.0–2.5) higher risk for iTTR< 65 % after EO, was accompanied by increased risk of bleeding (hazard ratio [HR] 2.1;CI 1.4–3.2), VKA-related death 17.0 (HR 17.0;CI 2.1–138) and thrombosis (HR 5.7;CI 1.5–22.2), compared to the 1600 controls. In conclusion, patients continuing VKA after EO have long-lasting inferior quality of VKA treatment despite intensified INR-monitoring, and an increased risk of bleeding, thrombosis and VKA-related death.Note: There have been no previous presentations, reports or publications of the complete data that appear in the article. Parts of the data in this article have been presented as a poster at the American Society of Hematology (ASH) congress 2013, New Orleans, United States.

Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants

2015 ◽  
Vol 114 (11) ◽  
pp. 1076-1084 ◽  
Author(s):  
Franziska Michalski ◽  
Luise Tittl ◽  
Sebastian Werth ◽  
Ulrike Hänsel ◽  
Sven Pannach ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Case Fatality ◽  
Bleeding Risk ◽  
Vitamin K Antagonist ◽  
Bleeding Complications ◽  
Treatment Rate

SummaryAtrial fibrillation (AF) patients treated with well-controlled vitamin K antagonists (VKAs) may benefit less from non-vitamin K antagonist oral anticoagulants (NOACs) because they are supposed to be at low risk of thromboembolic and bleeding complications. However, little is known about the selection, management, and outcome of such “stable” VKA patients in current practice. We assessed characteristics, VKA persistence and 12 months' outcome of AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC registry opened recruitment of patients continuing on VKA for sites that had been actively recruiting AF patients treated with NOACs in the prior 18 months. Patient characteristics were compared with those of NOAC patients from the same sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding risk profile compared with 706 patients selected for NOAC treatment. For VKA, international normalised ratio time-in-therapeutic range before enrolment was 71% and increased to 75% during a mean follow-up of 15 months. Rates of stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate of ISTH major bleeding was 4.15/100 patient-years (95% CI 2.60–6.29) with a case-fatality rate of 16.3% (all-cause mortality at day 90 after major bleeding). In conclusion, in daily care, AF patients selected for VKA therapy are healthier than those treated with NOAC, demonstrate a high quality of anticoagulant control and very low stroke rates. However, despite adequate patient selection and INR control, the risk of major VKA bleeding is unacceptably high and bleeding outcome is poor.

Vitamin K antagonists

2012 ◽  
Vol 32 (04) ◽  
pp. 249-257 ◽  
Author(s):  
T. F. Luscher ◽  
J. Steffel
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Drug Interactions ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Term Treatment ◽  
Thrombin Inhibitor ◽  
Long Term Treatment

SummaryFor the last decades, anticoagulation for stroke prevention in atrial fibrillation (AF) as well as for the prophylaxis and long-term treatment of venous thromboembolism has been entirely based on vitamin K antagonists (VKA). Although very effective under optimal conditions, long-term treatment with these drugs is flawed by the fact that the time in the therapeutic range frequently is suboptimal due to biological factors, drug interactions and compliance.The direct thrombin inhibitor dabigatran, as well as the direct FXa inhibitors rivaroxaban and apixaban provide more consistent anticoagulation and have proven their efficacy and safety against VKAs in several large scale randomized clinical trials for stroke prevention in atrial fibrillation as well as for the treatment and prevention of venous thromboembolism. In view of these convincing data and other advantages such as the lack of mandatory monitoring and only few drug interactions,VKAs will most likely be replaced in a majority of patients for these indications. Based on the most recent trial evidence, the current review discusses the role of VKA treatmentand that of the novel anticoagulants.

scholarly journals Direct Oral Anticoagulants after Ischemic Stroke: Which Patient? Which Drug? And How Early?

2021 ◽  
Vol 41 (01) ◽  
pp. 031-034
Author(s):  
Gian Marco De Marchis
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Vitamin K ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Reversal Agents

AbstractDirect oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and ischemic stroke. The main advantage of DOAC over VKA is the lower rate of bleeding and mortality. This review covers challenges clinicians can encounter when treating patients with AF and ischemic stroke, including timing of DOAC start and ongoing randomized clinical trials, appropriate dosing, and available comparative evidence across DOACs. For patients without AF but with an ischemic stroke, the review outlines the role of DOACs. Finally, the risk of thrombotic events associated with specific DOAC reversal agents and DOAC pausing is reviewed.

scholarly journals Stroke prevention for non-valvular atrial fibrillation: how to make the right choice of directly acting oral anticoagulants?

2019 ◽  
pp. 94-102
Author(s):  
N. N. Kryukov ◽  
E. V. Sayutina ◽  
A. M. Osadchuk ◽  
M. A. Osadchuk
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Vitamin K ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Individual Risk ◽  
Stroke Risk Factor ◽  
Coronary Syndrome

Patients with atrial fibrillation have a high risk of developing stroke and death, which requires constant anticoagulant support. In this regard, the physician faces the difficult task of selecting the appropriate oral anticoagulant for patient with individual risk factors and comorbidities. Currently, three non-vitamin K antagonist oral anticoagulants or directly acting oral anticoagulants have been registered in the Russia, which in large randomized clinical trials (RCTs) were compared with warfarin in the prevention of stroke and systemic embolism. The present article analyzes the data of RCTs, postmarketing studies of oral anticoagulants, and presents groups of patients for whom these drugs are preferred. The choice of oral anticoagulants for the prevention of stroke in the following subgroups of patients with atrial fibrillation is discussed: patients with one stroke risk factor (CHA2DS2VASc1 in men or 2 in women), patients of different age groups, patients with concomitant coronary artery disease/acute coronary syndrome, a history of stroke, patients with chronic kidney disease, patients with a high risk of gastrointestinal bleeding, and a group of patients with concomitant arterial hypertension and chronic heart failure. We compared the efficacy and safety of oral non-vitamin K antagonist oral anticoagulants or directly acting oral anticoagulants with vitamin K antagonists in patients with non-valvular atrial fibrillation.

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