Reduced stroke risk without increased bleeding risk in patients with atrial fibrillation and complicated liver cirrhosis treated with oral anticoagulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Steensig ◽  
M Pareek ◽  
A.L Krarup ◽  
P Sogaard ◽  
M Maeng ◽  
...  

Abstract Introduction Patients with atrial fibrillation (AF) have an increased risk of thromboembolic events (TE), while patients with complicated liver cirrhosis have an increased risk of both TE and bleeding. Oral anticoagulation reduces the risk of TE in the general group of patients with AF but its use in patients with liver cirrhosis is obscured by their imbalance between endogenous procoagulants and anticoagulants, as well as the lack of data from randomized controlled trials. Purpose To examine the risks of TE and bleeding in patients with AF and complicated liver cirrhosis according to whether oral anticoagulation is initiated. Methods We conducted a nationwide registry-based study of anticoagulant-naive patients with complicated liver cirrhosis and first-time AF diagnosed between 2010–2017. Complicated liver cirrhosis was defined as liver cirrhosis plus one of the following: alcoholism, esophageal varices, ascites or hepatorenal syndrome. Patients were followed for a maximum of 5 years. TE was defined as a composite of ischemic stroke, transient ischemic attack or systemic thromboembolism; and the bleeding endpoint was defined as gastrointestinal, cerebral or urogenital bleeding requiring hospitalization, or any hospital contact with epistaxis. TE risk was estimated by use of the CHA2DS2-VASc score, while bleeding risk was estimated by use of the HAS-BLED score. Outcomes were stratified according to whether an oral anticoagulant (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) was initiated. Results We identified 770 patients with complicated liver cirrhosis and first-time AF. TE events occurred in 7.0% (n=25/359) of patients with a CHA2DS2-VASc score ≤2 versus 20.7% (n=85/411) of patients with a CHA2DS2-VASc score >2. Among 411 patients with a high CHA2DS2-VASc score, 111 (27.0%) were prescribed an oral anticoagulant (OAC+; VKA, n=53 [47.7%], DOAC, n=58 [52.3%]), while 300 (73.0%) were not treated with oral anticoagulation (OAC−). These two groups had comparable baseline data, including HAS-BLED (OAC+ 3.0 [2.5–4.0] versus OAC− 3.0 [2.0–4.0]) and CHA2DS2-VASc (OAC+ 4.0 [3.0–5.0] versus OAC− 4.0 [3.0–5.0]) scores. The 5-year TE risk among patients receiving anticoagulant therapy was 14.4% (n=16/111) versus 23.0% (n=69/300) in patients not treated with anticoagulant therapy (hazard ratio (HR) 0.55 [0.32–0.95]). The difference in bleeding risk was insignificant between the two groups (HR 0.67 [0.35–1.30]). Adjusting for CHA2DS2-VASc, HAS-BLED and prior bleeding requiring hospitalization did not significantly change the HR estimate, and no significant interactions were found. Conclusion TE risk was significantly lower in AF patients with complicated liver cirrhosis treated with oral anticoagulation, without a significantly increased bleeding risk. However, the majority of AF patients with complicated liver cirrhosis are not treated with anticoagulant therapy, indicating a potential for reducing the TE burden in this population. Funding Acknowledgement Type of funding source: None

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319672
Author(s):  
Sharon Louise Cadogan ◽  
Emma Powell ◽  
Kevin Wing ◽  
Angel Yun Wong ◽  
Liam Smeeth ◽  
...  

ObjectiveThe aim of this study was to investigate the association between oral anticoagulant type (direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs)) and incident dementia or mild cognitive impairment (MCI) among patients with newly diagnosed atrial fibrillation (AF).MethodsUsing linked electronic health record (EHR) data from the Clinical Practice Research Datalink in the UK, we conducted a historical cohort study among first-time oral anticoagulant users with incident non-valvular AF diagnosed from 2012 to 2018. We compared the incidence of (1) clinically coded dementia and (2) MCI between patients prescribed VKAs and DOACs using Cox proportional hazards regression models, with age as the underlying timescale, accounting for calendar time and time on treatment, sociodemographic and lifestyle factors, clinical comorbidities and medications.ResultsOf 39 200 first-time oral anticoagulant users (44.6% female, median age 76 years, IQR 68–83), 20 687 (53%) were prescribed a VKA and 18 513 (47%) a DOAC at baseline. Overall, 1258 patients (3.2%) had GP-recorded incident dementia, incidence rate 16.5 per 1000 person-years. DOAC treatment for AF was associated with a 16% reduction in dementia diagnosis compared with VKA treatment in the whole cohort (adjusted HR 0.84, 95% CI: 0.73 to 0.98) and with a 26% reduction in incident MCI (adjusted HR 0.74, 95% CI: 0.65 to 0.84). Findings were similar across various sensitivity analyses.ConclusionsIncident EHR-recorded dementia and MCI were less common among patients prescribed DOACs for new AF compared with those prescribed VKAs.


Author(s):  
Carlos Bravo-Perez ◽  
M. Jose José Serna ◽  
Julio Esteban ◽  
Eugenia Fernandez-Mellid ◽  
Emilia Fontanes-Trabazo ◽  
...  

The bleeding phenotype of FXI deficiency is unpredictable. Bleeding is usually mild, and mostly occurs after injury. Although FXI deficiency renders antithrombotic protection, some patients might eventually develop thrombosis or atrial fibrillation, requiring anticoagulant therapy. There is almost no evidence on the bleeding risk in this scenario. Our retrospective study of 269 Caucasian FXI-deficient subjects (1995-2021) identified 15 cases requiring anticoagulation. They harbored eight different F11 variants, mainly in heterozygosis (one case was homozygote) and had mild-moderate deficiency (FXI:C:20-70%). Two subjects (13.3%) had bleeding history before anticoagulation. Atrial fibrillation was the main indication (12/15,80%). Fourteen patients started therapy with vitamin K antagonists (VKA), but four were on direct oral anticoagulants (DOACs) at the end of follow-up. Over more than 1000 months of anticoagulation, two mild bleeding episodes in two patients (13.3%,95%CI:3.7-37.9%) were recorded. No major/fatal events were reported. "Pre-post" bleeding localization and severity did not change despite treatment. On VKA, drug dosing and management were also standard, unaltered by FXI deficiency. We provide the largest description of anticoagulant use in FXI deficiency, and the first cases receiving DOACs. While further studies are needed, our observations suggest that moderate FXI deficiency does not interfere with anticoagulant management nor bleeding risk.


2018 ◽  
Vol 5 (1) ◽  
pp. 11
Author(s):  
Daniela Dobrovoljski

Oral anticoagulant drugs (OALs) are effective agents in the prevention and treatment of thromboembolic complications. However, despite standardization and application progression, OALs represent a significant clinical problem because they are small-therapeutic medicines that easily interact with food and medicine, which can substantially affect the increased or weakened therapeutic effect. Oral anticoagulants are 4-hydroxycoumarin derivatives and vitamin K antagonists, and their pharmacological activity is based on inhibition of the synthesis of coagulation factors in the liver. These drugs are effective in the prevention of venous thromboembolism, acute myocardial infarction (AIM), heart rhythm disorders by type of atrial fibrillation, stroke prevention, and the like. The most important and clinically commonly undesirable effect of OAL is bleeding. The risk of bleeding is greatest during the introduction of the drug in therapy and for the first few months of the onset of therapy. HAS-BLED scor is a skoring system developed to estimate the 1-year risk of major bleeding in patients with atrial fibrillation and is also used for other indications.


ABOUTOPEN ◽  
2018 ◽  
Vol 4 (1) ◽  
pp. 154-157
Author(s):  
Roberto Spoladore

Trans-catheter ablation of atrial fibrillation (AF) is a common treatment for symptomatic AF. Among the major complications of AF ablation are stroke, transient ischemic attacks and peri-procedural cardiac tamponade. Various clinical trials have shown that uninterrupted treatment with vitamin K antagonists (VKA) is associated with a lower incidence of embolic events compared to discontinuation of therapy; until recently, in the absence of equally solid evidence, this practice was not extended to the new oral anticoagulants (NOAC) not VKA due to the fear of hemorrhagic complications potentially associated with the use of an "irreversible" anticoagulant. The case of a patient suffering from numerous comorbidities is reported here. In light of the poor response to anti-arrhythmics, a TC-RF ablation was performed, with suspension of dabigatran administration only on the day of the procedure (for a total period <24 hours). Although the fear of the risk of bleeding potentially associated with the trans-catheter ablation procedure may still induce clinicians to stop anticoagulant therapy, even the decision to discontinue anticoagulant therapy with dabigatran on the day of surgery alone is challenged by recent evidence in the literature supporting the efficacy of dabigatran in reducing the incidence of hemorrhagic events during and after ablation, including the results of the RE-CIRCUIT study (Cardiology)


2020 ◽  
Vol 73 (11) ◽  
pp. 2528-2534
Author(s):  
Dagmara Wojtowicz ◽  
Anna Tomaszuk-Kazberuk ◽  
Jolanta Małyszko ◽  
Marek Koziński

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.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Hong Seok Lee

Background: Oral anticoagulants known as a novel oral anticoagulant have been used for the management of non -valvular atrial fibrillation. There was no enough study regarding the efficacy and safety of three major new oral anticoagulants. We assessed major three oral anticoagulants in terms of major bleeding complication and stroke prevention by meta-analyses studies comparing those drugs. Method: Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2016). RevMan and ITC software were used for direct comparisons, respectively. Results: Apixaban (N=6020), versus dabigatran(N=12038), apixaban versus rivaroxaban(N=8503) and rivaroxaban versus dabigatran were analyzed directly. There was significantly higher major bleeding risks in apixaban compared to dabigatran (both 110mg and 150mg) after adjusting baseline bleeding risk (Relative risk 3.41, 95% confidence interval(2.61 to 4.47) in 110mg, (5.62, 4.83 to 6.54) in 150mg. Intracranial bleeding risk in apixaban was significantly higher than in dabigatran (10.5, 6.10 to18.01). However, apixaban had less GI bleeding risk compared to dabigatran (0.80 , 0.65 to 0.98) and also had less ischemic stroke risk (0.31,0.22 to 0.42). Rivaroxaban showed higher major bleeding risk than dabigatran 110mg (2.34 , 1.81 to 3.03), however, Rivaroxaban had less bleeding risk compared to dabigatran 150mg (0.41, 0.35 to 0.46). Dabigatran 110mg and 150mg had less GI bleeding risk compared to rivaroxaban (0.31 , 0.24 to 0.39) and (0.23,0.17 to 0.29) respectively. Ischemic stroke risk was also decreased in dabigatran110mg (0.46, 0.38 to 0.57). and 150mg (0.66 ,0.52 to 0.83). Conclusion: Observed oral anticoagulants were associated with various complications. Overall, apixaban had higher intracranial bleeding risk than dabigatran. The highest GI bleeding risk in rivaroxaban compared to apixaban and dabigatran. Ischemic stroke risk was the highest in dabigatran. In conclusion, we may use those oral anticoagulant based on risks rates, however, a larger study with longer follow-up is needed to corroborate findings.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J J Komen ◽  
P Hjemdahl ◽  
A K Mantel - Teeuwisse ◽  
O H Klungel ◽  
B Wettermark ◽  
...  

Abstract Background Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. Antidepressants use is associated with increased risk for stroke and bleeds. Objective To assess the association between antidepressant use in AF patients with oral anticoagulants and bleeding and stroke risk. Methods All AF patients newly prescribed with an oral anticoagulant in the Stockholm Healthcare database (n=2.3 million inhabitants) from July 2011 until 2016 were included and followed for one year or shorter if they stopped claiming oral anticoagulant treatment or had an outcome of interest. Outcomes were severe bleeds and strokes, requiring acute hospital care. During follow-up, patients were considered exposed to antidepressant after claiming a prescription for the duration of the prescription. With a time-varying Cox regression, we assessed the association between antidepressant use and strokes and bleeds, adjusting for confounders (i.e., age, sex, comorbidities, comedication, and year of inclusion). In addition, we performed a propensity score matched analysis to test the robustness of our findings. Results Of the 30,595 patients included after claiming a prescription for a NOAC (n=13,506) or warfarin (n=17,089), 4 303 claimed a prescription for an antidepressant during follow-up. A total of 712 severe bleeds and 551 strokes were recorded in the cohort. Concomitant oral anticoagulant and antidepressant use was associated with increased rates of severe bleeds (4.7 vs 2.7 per 100 person-years) compared to oral anticoagulant treatment without antidepressant use (aHR 1.42, 95% CI: 1.12–1.80), but not significantly associated with increased stroke rates (3.5 vs 2.1 per 100 person-years, aHR 1.23, 95% CI: 0.93–1.62). No significant differences were observed between different oral anticoagulant classes (i.e., warfarin or NOAC) or different antidepressant classes (i.e., SSRI, TCA, or other antidepressant). Additional propensity-score matched analyses yielded similar results but showed a significantly increased risk for stroke (HR: 1.47, 95% CI: 1.08–2.02). Incidence rates of strokes and bleeds Conclusion Concomitant use of an oral anticoagulant and an antidepressant, irrespective of type, is associated with an increased bleeding risk. Increased awareness and a critical consideration for the need of an antidepressant is recommended in this population. Acknowledgement/Funding Swedish Heart Lung Foundation


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Chilian-Hof ◽  
S Schnupp ◽  
C Mahnkopf ◽  
J Brachmann ◽  
C Kleinecke

Abstract Background Atrial fibrillation (AF) is the most frequent arrhythmia with a prevalence of 1%–2% in the general population. Oral anticoagulation (OAC) is state-of-the art for preventions of thromboembolic events, in particular ischemic stroke, in patients with atrial fibrillation. Despite its proven benefit, numerous studies have documented under use of OAC for a variety of reasons. Purpose To establish a program of nurse counseling in patient with atrial fibrillation and treatment with oral anticoagulation. The program is designed to improve patients satisfaction, compliance to OAC, prevention of medication errors, ischemic and bleeding events. Methods Patients with atrial fibrillation and treatment with oral anticoagulation were prospectively identified at the department of cardiology of our clinic. They received a 30 minutes nurse counseling about oral anticoagulation during the hospital stay and another 30 minutes telephone counseling 3 months after inclusion. Furthermore, they received a brochure to inform about atrial fibrillation, oral anticoagulation and methods to improve medication compliance. Demographic characteristics with stroke and bleeding risk (CHA2DS2-VASc and HAS-BLED scores), as well as procedural data were systematically assessed in a predefined standardized way and captured in a dedicated database. Results Between June 2017 and January 2018, a total of 617 patients (female gender: 43.1%) with atrial fibrillation and oral anticoagulation received nurse counseling. Demographic and follow-up data of 204 patients (female gender: 85/204 (41.7%); mean age 69.7±17.3, CHA2DS2-VASc score 4.2±1.7, HAS-BLED score 2.8±0.37) were assessed in a dedicated database. Indication for OAC was paroxysmal and persistent/permanent AF in 110/204 (53.9%), 93/204 (45.6%) and others 17 (8.3%), respectively. 33/2014 (16.2%) were treated with vitamin K antagonists, and 172/204 (84.3%) with non-vitamin K antagonists. After a follow-up of 0.46±2.9 years and 187 patients-years the rates of cardiovascular death, major bleeding events and all-cause stroke and TIA were 1.07%, 2.14% and 1.61% per 100 patient-years. Conclusion Nurse counseling in patients with atrial fibrillation and treatment with oral anticoagulation has been established at the REGIOMED clinics, Germany. Its effectiveness in terms of quality of live, medication complications and cardiovascular events has to be proven in a randomised trial. Acknowledgement/Funding Daichi-Sankyo


2020 ◽  
Vol 25 (5) ◽  
pp. 391-398
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Angelo Leone ◽  
Stefano Poli ◽  
...  

Antithrombotic drugs, which include antiplatelets and anticoagulants, are effective in prevention and treatment of many cardiovascular disorders such as acute coronary syndromes, stroke, and venous thromboembolism and are among the drugs most commonly prescribed worldwide. The advent of direct oral anticoagulants, which are safer alternatives to vitamin K antagonists and do not require laboratory monitoring, has revolutionized the treatment of nonvalvular atrial fibrillation and venous thromboembolism. The combination of oral anticoagulant and antiplatelet therapy is required in many conditions of great clinical impact such as the coexistence of atrial fibrillation and coronary artery disease, with indication to percutaneous coronary intervention. However, strategies that combine anticoagulant and antiplatelet therapies lead to a significant increase in bleeding rates and it is crucial to find the right combination in the single patient in order to optimize the ischemic and bleeding risk. The aim of this review is to explore the evidence and controversies regarding the optimal combination of anticoagulant and antiplatelet therapy through the consideration of past dogmas and new perspectives from recent clinical trials and to propose a tailored therapeutic approach, according to specific clinical scenarios and individual patient characteristics. In particular, we separately explored the clinical settings of stable and acute coronary syndromes and percutaneous revascularization in patients with atrial fibrillation.


2020 ◽  
Vol 29 (02) ◽  
pp. 088-097
Author(s):  
Anwar Santoso ◽  
Sunu B. Raharjo

AbstractAtrial fibrillation (AF), the most prevalent arrhythmic disease, tends to foster thrombus formation due to hemodynamic disturbances, leading to severe disabling and even fatal thromboembolic diseases. Meanwhile, patients with AF may also present with acute coronary syndrome (ACS) and coronary artery disease (CAD) requiring stenting, which creates a clinical dilemma considering that majority of such patients will likely receive oral anticoagulants (OACs) for stroke prevention and require additional double antiplatelet treatment (DAPT) to reduce recurrent cardiac events and in-stent thrombosis. In such cases, the gentle balance between bleeding risk and atherothromboembolic events needs to be carefully considered. Studies have shown that congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, and previous stroke or transient ischemic attack (TIA; doubled)–vascular disease, age 65 to 74 years, sex category (female; CHA2DS2-VASc) scores outperform other scoring systems in Asian populations and that the hypertension, abnormal renal/liver function (1 point each), stroke, bleeding history or predisposition, labile international normalized ratio (INR), elderly (>65 years), drugs/alcohol concomitantly (1 point each; HAS-BLED) score, a simple clinical score that predicts bleeding risk in patients with AF, particularly among Asians, performs better than other bleeding scores. A high HAS-BLED score should not be used to rule out OAC treatment but should instead prompt clinicians to address correctable risk factors. Therefore, the current review attempted to analyze available data from patients with nonvalvular AF who underwent stenting for ACS or CAD and elaborate on the direct-acting oral anticoagulant (DOAC) and antiplatelet management among such patients. For majority of the patients, “triple therapy” comprising OAC, aspirin, and clopidogrel should be considered for 1 to 6 months following ACS. However, the optimal duration for “triple therapy” would depend on the patient's ischemic and bleeding risks, with DOACs being obviously safer than vitamin-K antagonists.


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