scholarly journals Practice-derived data on non-vitamin K antagonist oral anticoagulant therapy to complement observations from randomized trials

2020 ◽  
Vol 22 (Supplement_I) ◽  
pp. I1-I12
Author(s):  
Magdalena Domek ◽  
Jakub Gumprecht ◽  
Wern Yew Ding ◽  
Gregory Y H Lip ◽  
Deirdre A Lane
Keyword(s):  
Vitamin K ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Strong Support ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Increased Risk ◽  
Comparative Review

Abstract Anticoagulation is fundamental in the management of patients with atrial fibrillation (AF). The study aims to provide a comparative review of the major phase III randomized clinical trials (RCTs) and real-world data (RWD) from reliable, high-grade Phase IV studies that assess the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) vs. vitamin K antagonists (VKAs). Observational studies based on nationwide or health insurance database records on the use of NOACs vs. VKAs in patients with AF were included. We performed a comparison of the efficacy and safety characteristics associated with NOACs vs. VKAs in RCTs and RWD. Although RCTs provide strong support for evidence-based practice, RWD may be used to reflect the broader picture of various clinical settings, provide supplementary insight and fulfil knowledge gaps. Both study types confirmed the safety and efficacy of NOACs in preventing stroke and thromboembolism in patients with AF. In comparison to VKAs, NOACs were associated with reduced risk of ischaemic events and lower rates of adverse events such as major bleeding or intracranial haemorrhage. Administration of NOACs might be associated with increased risk of dose-related gastrointestinal bleeding and myocardial ischaemic events, especially in the early treatment period after switching from VKAs. Special care should be taken in challenging clinical situations like severe renal or hepatic impairment when the treatment regimen needs to be considered individually. Randomized clinical trial and RWD studies are complementary and present comparable findings, affirming that NOACs are safe and effective for anticoagulation of patients with AF in daily clinical practice.

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.

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.

scholarly journals Men who live alone have high risk of NOAC discontinuation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Binding ◽  
J.B Olesen ◽  
C Lee ◽  
C Sindet-Petersen ◽  
C.T Pedersen ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Male Gender ◽  
Living Alone ◽  
Funding Source ◽  
Hazard Ratios ◽  
Increased Risk ◽  
And Gender

Abstract Background/Introduction Patients with atrial fibrillation (AF), who are considered at risk of stroke, are treated with oral anticoagulants (OACs), and non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists in recent guidelines. Poor NOAC compliance among patients with AF could result in an increased risk of thromboembolism and major bleeding, however, it has yet to be evaluated how cohabitant status and gender affects compliance with NOAC treatment among patients with AF. Purpose The aim of this study was to evaluate the risk of NOAC discontinuation among patients with AF according to cohabitant status and gender. Methods Using the Danish national registries we identified and included patients with AF aged 40–90 years in treatment with NOAC. The study period was from 2013 to 2017, and patients were followed for two years, or until death, outcome or emigration. The main outcome was discontinuation of NOAC-treatment for at least 30 days. Absolute risks were calculated as cumulative incidences using the Aalen Johansen estimator, and multiple covariate adjusted Cox regressions were used to calculate hazard ratios (HR). Results We included 32,380 patients with AF in NOAC treatment, where 16.8% were men living alone (median age 72 years), 25.8% were women living alone (median age 79 years), 37.2% were men living with a partner (median age 70 years), and 20.2% were women living with a partner (median age 79 years). Absolute two-year risk of NOAC discontinuation was highest among men living alone (Cumulative Incidence (CI) 0.19; 95% CI: 0.17 to 0.20), followed by men living with a partner (CI 0.18; 0.17 to 0.19), women living with a partner (CI 0.16; 0.15 to 0.17), and women living alone (CI 0.13; 0.12 to 0.14). After adjustment, living alone was associated with an increased risk of NOAC discontinuation among men (HR 1.15, 95% CI: 1.05 to 1.26), but not among women (HR 1.04, 95% CI: 0.93 to 1.15, interaction p=0.32). In an analysis evaluating gender, we found that being male was associated with a significantly higher risk of NOAC-discontinuation (HR 1.18, CI: 1.10 to 1.25) compared to women. Results were similar when we used 60 days discontinuation instead of 30 days discontinuation as outcome. Conclusion Gender and cohabitant status was significantly associated with risk of NOAC discontinuation. Male gender and living alone was associated with a higher risk of NOAC discontinuation among patients with AF in a nationwide population. Adjusted relative two-year risks Funding Acknowledgement Type of funding source: None

scholarly journals Safety and differences between direct oral anticoagulants and vitamin K antagonists in the risk of post-traumatic intrathoracic bleeding after rib fractures in elderly patients

2021 ◽  
Vol 17 (4) ◽  
Author(s):  
Gianni Turcato ◽  
Arian Zaboli ◽  
Andrea Tenci ◽  
Giorgio Ricci ◽  
Massimo Zannoni ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Vitamin K ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Traumatic Bleeding ◽  
Post Traumatic

Closed chest traumas are frequent consequences of falls in the elderly. The presence of concomitant oral anticoagulant therapy can increase the risk of post-traumatic bleeding even in cases of trauma with non-severe dynamics. There is limited information about the differences between vitamin K antagonists and direct oral anticoagulants in the risk of post-traumatic bleeding. To assess differences in the risk of developing intra-thoracic hemorrhages after chest trauma with at least one rib fracture caused by an accidental fall in patients over 75 years of age taking oral anticoagulant therapy. This study involved data from four emergency departments over two years. All patients on oral anticoagulant therapy and over 75 years of age who reported a closed thoracic trauma with at least one rib fracture were retrospectively evaluated. Patients were divided into two study groups according their anticoagulant therapy. Of the 342 patients included in the study, 38.9% (133/342) were treated with direct oral anticoagulants and 61.1% (209/342) were treated with vitamin K antagonist. A total of 7% (24/342) of patients presented intrathoracic bleeding, while 5% (17/342) required surgery or died as a result for the trauma. Posttraumatic intrathoracic bleeding occurred in 4.5% (6/133) of patients receiving direct oral anticoagulants and 8.6% (18/209) of patients receiving vitamin K antagonist. Logistic regression analysis, revealed no difference in the risk of intrathoracic haemorrhages between the two studied groups. Direct oral anticoagulants therapy presents a risk of post-traumatic intrathoracic haemorrhage comparable to that of vitamin K antagonist therapy.

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.

scholarly journals Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation and Cancer in Real World: Meta-Analysis of Retrospective Observational Studies

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Cao B ◽  
Hu X ◽  
Chen M ◽  
Shen M ◽  
Xu L
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Real World ◽  
Observational Studies ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Efficacy And Safety ◽  
Patients With Cancer

Background: Evidence on the safety and effectiveness of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) in Atrial Fibrillation (AF) patients with cancer is rather limited, so we performed this meta-analysis to compare the efficacy and safety of NOACs with vitamin K antagonists (VKAs) in real-world patients with AF and cancer.

Overcoming global challenges in stroke prophylaxis in atrial fibrillation: The role of non-vitamin K antagonist oral anticoagulants

2016 ◽  
Vol 11 (9) ◽  
pp. 950-967 ◽  
Author(s):  
Ayrton Massaro ◽  
Robert P Giugliano ◽  
Bo Norrving ◽  
Ali Oto ◽  
Roland Veltkamp
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Health Care Systems ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Ageing Population ◽  
Maximum Benefit ◽  
Increased Risk ◽  
Care Systems

Atrial fibrillation is the world's most common sustained cardiac arrhythmia and is associated with a significantly increased risk of stroke. The global burden of atrial fibrillation is rising, commensurate with the ageing population. Well-controlled vitamin K antagonist-based anticoagulation has been shown to reduce the risk of stroke secondary to atrial fibrillation by two-thirds. However, patients with atrial fibrillation have frequently been denied anticoagulation because of a variety of perceived risks related to bleeding, falls, chronological age, and poor compliance. Even when vitamin K antagonists are used, maximum benefit and safety are only delivered when high quality control of therapy (TTR > 70%) is achieved, which has proven remarkably difficult in many health-care systems and amongst many patient groups. The non-vitamin K antagonist oral anticoagulants (NOACs) offer solutions to many of the challenges of achieving widespread, safe, and effective anticoagulation for stroke prophylaxis in atrial fibrillation, yet their uptake into routine clinical practice remains variable. The evidence supporting their more widespread use to overcome the challenges of stroke prophylaxis for atrial fibrillation is reviewed in this article.

scholarly journals Treatment of intracerebral hemorrhage: From specific interventions to bundles of care

2020 ◽  
Vol 15 (9) ◽  
pp. 945-953
Author(s):  
Adrian R Parry-Jones ◽  
Tom J Moullaali ◽  
Wendy C Ziai
Keyword(s):  
Intracerebral Hemorrhage ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
Hematoma Expansion ◽  
Care Bundle ◽  
Do Not Resuscitate ◽  
Risk Of Death ◽  
Increased Risk

Intracerebral hemorrhage (ICH) represents a major, global, unmet health need with few treatments. A significant minority of ICH patients present taking an anticoagulant; both vitamin-K antagonists and increasingly direct oral anticoagulants. Anticoagulants are associated with an increased risk of hematoma expansion, and rapid reversal reduces this risk and may improve outcome. Vitamin-K antagonists are reversed with prothrombin complex concentrate, dabigatran with idarucizumab, and anti-Xa agents with PCC or andexanet alfa, where available. Blood pressure lowering may reduce hematoma growth and improve clinical outcomes and careful (avoiding reductions ≥60 mm Hg within 1 h), targeted (as low as 120–130 mm Hg), and sustained (minimizing variability) treatment during the first 24 h may be optimal for achieving better functional outcomes in mild-to-moderate severity acute ICH. Surgery for ICH may include hematoma evacuation and external ventricular drainage to treat hydrocephalus. No large, well-conducted phase III trial of surgery in ICH has so far shown overall benefit, but meta-analyses report an increased likelihood of good functional outcome and lower risk of death with surgery, compared to medical treatment only. Expert supportive care on a stroke unit or critical care unit improves outcomes. Early prognostication is difficult, and early do-not-resuscitate orders or withdrawal of active care should be used judiciously in the first 24–48 h of care. Implementation of acute ICH care can be challenging, and using a care bundle approach, with regular monitoring of data and improvement of care processes can ensure consistent and optimal care for all patients.

scholarly journals Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer associated thrombosis: a meta-analysis of randomized controlled trials

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ruchi Desai ◽  
Gautam Krishna Koipallil ◽  
Nelson Thomas ◽  
Rahul Mhaskar ◽  
Nathan Visweshwar ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Increased Risk ◽  
Recurrent Vte ◽  
Cancer Associated Thrombosis

Abstract Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51–0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40–0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44–1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78–2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13–2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10–2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.

Sign in / Sign up

Export Citation Format

Share Document