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 New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact

2021 ◽  
Vol 8 ◽  
Author(s):  
Eve Cariou ◽  
Kevin Sanchis ◽  
Khailène Rguez ◽  
Virginie Blanchard ◽  
Stephanie Cazalbou ◽  
...  
Keyword(s):  
Vitamin K ◽  
Cardiac Amyloidosis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Bleeding Complications ◽  
Prognostic Impact ◽  
Transthyretin Amyloidosis ◽  
Increased Risk ◽  
All Cause Mortality ◽  
History Of

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA.Methods and Results: 273 patients with CA and history of AA with long term anticoagulation−69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)–were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality.Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.

Non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in (morbidly) obese or low body weight patients with atrial fibrillation: a meta-analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Grymonprez ◽  
TL De Backer ◽  
S Steurbaut ◽  
K Boussery ◽  
L Lahousse
Keyword(s):  
Body Weight ◽  
Cohort Studies ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
Morbidly Obese ◽  
Class Iii ◽  
Observational Cohort

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fund for Scientific Research Flanders (FWO) Background Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Moreover, VKAs are still recommended in morbidly obese patients (body mass index (BMI) ≥40 kg/m², body weight >120 kg) due to lack of data for NOACs in these patients. Purpose A critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum.  Methods After searching the Medline database, phase III randomized controlled trials (RCTs) and longitudinal observational cohort studies on the effectiveness and safety of NOACs versus VKAs in obese (BMI ≥30 kg/m²), and class III obese (BMI ≥40 kg/m²) non-valvular AF patients, and in low body weight (≤60 kg) AF patients during a mean/median follow-up of ≥6 months were included. The meta-analyses were performed using a random effects model with the Mantel-Haenszel method. Results A meta-analysis based on 4 phase III RCTS and 3 longitudinal observational cohort studies demonstrated that NOAC use in obese and class III obese AF patients was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96]; and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00]; and RR 0.74, 95%CI [0.57-0.95], respectively), and similar mortality risks (RR 0.92, 95%CI [0.73-1.15]; and RR 1.17, 95%CI [0.83-1.64], respectively) as compared to VKAs. In AF patients ≤60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), and similar mortality risks (RR 0.68, 95%CI [0.42-1.10]) were observed for NOAC- versus VKA-treated patients in a meta-analysis based on 4 phase III RCTs and 2 longitudinal observational cohort studies. Conclusions The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight of ≤60 kg. However, more data are needed in underweight AF patients (BMI <18.5 kg/m²) and on differences between NOACs to further optimize management in these patient subgroups.

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.

RE-COVERY DVT/PE: Rationale and design of a prospective observational study of acute venous thromboembolism with a focus on dabigatran etexilate

2017 ◽  
Vol 117 (02) ◽  
pp. 415-421 ◽  
Author(s):  
Walter Ageno ◽  
Ivan B. Casella ◽  
Chee Kok Han ◽  
Gary E. Raskob ◽  
Sebastian Schellong ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K ◽  
Large Scale ◽  
Vitamin K Antagonists ◽  
Phase 1 ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
Real World Data ◽  
Phase Iii Studies

SummaryThe therapeutic management of venous thromboembolism (VTE) is rapidly evolving. Following the positive results of pivotal large-scale randomised trials, the non-vitamin K antagonist oral anticoagulants (NOACs) represent an important alternative to standard anticoagulation. In phase III studies, dabigatran was as effective as, and significantly safer than warfarin. Additional information on real-world data of dabigatran is now warranted. RE-COVERY DVT/PE is a multi-centre, international, observational (i. e. non-interventional) study enrolling patients with acute DVT and/or PE within 30 days after objective diagnosis. The study is designed with two phases. Phase 1 has a cross-sectional design, enrolling approximately 6000 patients independently of treatment choice, with the aim of providing a contemporary picture of the management of VTE worldwide. Phase 2 has a prospective cohort design, with follow-up of one year, enrolling 8000 patients treated with dabigatran or vitamin K antagonists (VKAs) with the aim of comparing their safety, defined by the occurrence of major bleeding, and effectiveness, defined by the occurrence of symptomatic recurrent VTE. RE-COVERY DVT/PE will complement both the results of other observational studies in this field and the results of phase III studies with dabigatran, in particular by assessing its clinical benefit in various patient subgroups treated in routine clinical practice.

scholarly journals Ten years of non-vitamin K antagonists oral anticoagulants for stroke prevention in atrial fibrillation: is warfarin obsolete?

2020 ◽  
Vol 22 (Supplement_O) ◽  
pp. O28-O41
Author(s):  
Matthias Hammwöhner ◽  
Andreas Goette
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Data ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Study Data ◽  
Phase Iii ◽  
Clinical Settings ◽  
Specific Patient

Abstract Currently, four non-vitamin K antagonists oral anticoagulants (NOACs) are available for stroke prevention in atrial fibrillation (AF). These have been in clinical use for up to 10 years now. Besides data of the initial phase III clinical trials, now clinical data, several sub-studies, meta-analyses, and studies in special clinical settings and specific patient populations are available. This review shall give an overview on the history of NOAC development, sum up study data and ‘real-world’ clinical data as well as discuss several special clinical settings like NOAC treatment in patients that require coronary artery stenting or cardioversion (CV). Furthermore, treatment considerations in special patient populations like patients with renal impairment, obesity, or patients requiring NOACs for secondary prevention are discussed. The significance of NOAC treatment will be discussed under consideration of the recently published 2020 ESC/EACTS Guidelines for the diagnosis and management of AF.

Dabigatran treatment simulation in patients undergoing maintenance haemodialysis

2016 ◽  
Vol 115 (03) ◽  
pp. 562-569 ◽  
Author(s):  
Joerg Kreuzer ◽  
Martina Brueckmann ◽  
Friedrich Schulze ◽  
Karl-Heinz Liesenfeld ◽  
Andreas Clemens
Keyword(s):  
Renal Clearance ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Area Under The Curve ◽  
Fold Increase ◽  
Dose Selection ◽  
Maintenance Haemodialysis ◽  
Increased Risk

SummaryPatients with atrial fibrillation requiring maintenance haemodialysis are at increased risk of ischaemic stroke and bleeds. Currently, vitamin K antagonists such as warfarin are predominantly used in these patients as limited data are available on the use of non-vitamin K oral anticoagulants, including dabigatran etexilate (dabigatran). Dabigatran is approximately 85 % renally eliminated, thus, its half-life is prolonged in renal impairment. This study simulated the dose-exposure relationship of dabigatran in patients undergoing haemodialysis. Dabigatran exposure was modelled at once- and twice-daily doses of 75 mg, 110 mg and 150 mg and at variations in non-renal clearance and dialysis settings. Resultant dose exposure (area under the curve [AUC]) was compared with values simulated from typical patients in the RE-LY® trial (based on a previously characterised pharmacometric model). In this simulation, all twice-daily dosages resulted in exposures above those simulated from typical RE-LY patients (1.5- to 3.3-fold increase in AUC) and thus may not be optimal for use in haemodialysis patients. However, dabigatran doses of 75 mg or 110 mg once daily produced exposures comparable to those simulated in typical RE-LY patients (-13.3 and +4.4 %, respectively). Of patient and dialysis variables, non-renal clearance had the highest impact on exposure (≤30.8 % change). These data could potentially inform dose selection in patients undergoing maintenance haemodialysis and the findings warrant investigation in future clinical trials.

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants

2016 ◽  
Vol 12 (6) ◽  
pp. 623-627 ◽  
Author(s):  
Cláudia Marques-Matos ◽  
José Nuno Alves ◽  
João Pedro Marto ◽  
Joana Afonso Ribeiro ◽  
Ana Monteiro ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Intracranial Hemorrhage ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Vitamin K Antagonist ◽  
Significant Shift ◽  
Modified Rankin Scale

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA2DS2VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39–1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55–2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants- and vitamin K antagonists-associated intracranial hemorrhage, despite unavailability of non-vitamin K antagonist oral anticoagulants-specific reversal agents.

scholarly journals Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies

2017 ◽  
Vol 38 (06) ◽  
pp. 726-736 ◽  
Author(s):  
Lanting Fuh ◽  
Jonathan Sin ◽  
Joshua Goldstein ◽  
Bryan Hayes
Keyword(s):  
Intracerebral Hemorrhage ◽  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Quality Data ◽  
Reversal Agent ◽  
Intravenous Vitamin ◽  
Time Of Presentation

AbstractIn patients with acute intracerebral hemorrhage (ICH), one of the major concerns is ongoing bleeding or ICH expansion. Anticoagulated patients are at higher risk of ongoing expansion and worse outcome. It may be that rapid anticoagulation reversal can reduce the risk of expansion and improve clinical outcome. For those taking coumarins, the best available evidence suggests that intravenous vitamin K combined with four-factor prothrombin complex concentrate (4F-PCC) is the most rapid and effective regimen to restore hemostasis. For those on dabigatran, the highest quality data available for reversal are for idarucizumab, although it is not yet clear whether patients derive clinical benefit from this reversal. In the absence or failure of idarucizumab, activated prothrombin complex concentrate (aPCC) is recommended. For those on factor Xa inhibitors, the ideal reversal agent is not clear. Many providers use 4F-PCC or aPCC, but more specific agents are in clinical trials and may soon be available. In addition, the half-lives of the non–vitamin K antagonists are relatively short compared with warfarin, and so some patients may not have a clinically relevant coagulopathy at the time of presentation. Overall, the optimal reversal agent, when one is required, is a function of which anticoagulant the patient is taking.

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

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