scholarly journals Anticoagulant therapy in patients with congenital FXI deficiency

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.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Pardo Sanz ◽  
L M Rincon ◽  
P Guedes Ramallo ◽  
L Belarte ◽  
G De Lara ◽  
...  

Abstract Aims Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. We further evaluated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with cancer. Methods The AMBER-AF registry is an observational multicentre study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain. 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. Mean follow-up was 3.1 years. Results Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. Lack of guidelines recommended therapies was more frequent among patients with cancer. Compared with patients without cancer, adjusted rates of stroke (hazard ratio [95% confidence interval]) in cancer patients were higher (1.56 [1.04–2.35]), whereas bleeding rates remained similar (1.25 [0.95–1.64]). Within the group of patients with cancer, the use of DOACs vs VKAs did not entail differences in the adjusted rates of stroke (0.91 [0.42–1.99]) or severe bleedings (1.53 [0.93–2.53]). Follow-up events Conclusions Antithrombotic management of AF frequently differs in patients with breast cancer. While breast cancer is associated with a higher risk of incident stroke, bleeding events remained similar. Patients with cancer treated with DOACs experienced similar rates of stroke and bleeding as those with VKAs.


2020 ◽  
Vol 25 (4) ◽  
pp. 316-323
Author(s):  
Martín Ruiz Ortiz ◽  
Javier Muñiz ◽  
María Asunción Esteve-Pastor ◽  
Francisco Marín ◽  
Inmaculada Roldán ◽  
...  

Objective: To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Methods: A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received. Results: Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%, P = .01), cancer history (4.9% vs 10.9%, P = .046), renal failure (21.1% vs 32.2%, P = .02), and left ventricular dysfunction (2.4% vs 8.0%, P = .03); and higher frequency of previous stroke (26.0% vs 16.6%, P = .02) and previous major bleeding (8.1% vs 3.6%, P = .03). There were no significant differences in Charlson, CHA2DS2VASc, nor HAS-BLED scores. At 3-year follow up, rates of embolic events, severe bleedings, and all-cause death (per 100 patients-year) were similar in both groups (DOACs vs VKAs): 0.34 vs 1.35 ( P = .15), 3.45 vs 4.41 ( P = .48), and 8.2 vs 11.0 ( P = .18), respectively, without significant differences after multivariate analysis (hazard ratio [HR]: 0.25, 95% confidence interval [CI]: 0.03-1.93, P = .19; HR: 0.88, 95% CI: 0.44-1.76, P = .72 and HR: 0.84, 95% CI: 0.53-1.33, P = .46, respectively). Conclusion: In this “real-world” registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.


2019 ◽  
Vol 15 (1) ◽  
pp. 49-53
Author(s):  
V. I. Petrov ◽  
O. V. Shatalova ◽  
A. S. Gerasimenko ◽  
V. S. Gorbatenko

Aim. To study the frequency of prescribing antithrombotic agents in patients with non-valvular atrial fibrillation (AF) who were hospitalized in the cardiology department of a multidisciplinary hospital.Material and methods. A retrospective one-time study of medical records of 765 patients with non-valvular AF treated in the cardiology department of a multidisciplinary hospital in 2012 and 2016 was performed.Results. All patients were stratified in three groups depending on the CHA2DS2-VASc score. The frequency of prescribing antithrombotic agents was evaluated in each group. A low risk of thromboembolic complications was found in 1% (n=3) of patients in 2012 and 0.6% (n=3) in 2016. All these patients received antithrombotic agents. CHA2DS2-VASc=1 was found in 6% (n=15) of patients with AF in 2012 and in 3.4% (n=17) in 2016. A significant number of patients in this group received anticoagulant therapy with vitamin K antagonists (warfarin) or with direct oral anticoagulants. A high risk of thromboembolic complications (CHA2DS2-VASc≥2) was found in 93% of patient (n=245) in 2012 and in 96% (n=482) in 2016. Anticoagulant therapy was prescribed in 70.2% (n=172) patients with high risk in 2012 and 80% (n=387) in 2016. However, some patients with high risk of thromboembolic complications did not have the necessary therapy.Conclusion. Positive changes in the structure and frequency of prescribing anticoagulant drugs in patients with AF and a high risk of thromboembolic complications were found during the years studied. 


Heart ◽  
2020 ◽  
pp. heartjnl-2020-317923 ◽  
Author(s):  
Olivier Hanon ◽  
Jean-Sébastien Vidal ◽  
George Pisica-Donose ◽  
Galdric Orvoën ◽  
Jean-Philippe David ◽  
...  

ObjectiveDirect oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years.MethodsWe performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models.ResultsMajor bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score–matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score–matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding.ConclusionsOur study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.


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


2021 ◽  
Author(s):  
Noriko Tsuji ◽  
Yoshimitsu TAKAHASHI ◽  
Michi Sakai ◽  
Shosuke Ohtera ◽  
Junji Kaneyama ◽  
...  

Abstract Background and aim: The introduction of direct oral anticoagulants (DOACs) has greatly changed the use of anticoagulant therapy in patients with non-valvular atrial fibrillation (Af). However, few studies have reported on the current state of anticoagulant therapy at the national level. This study aimed to examine changes in the proportions of oral anticoagulant (OAC) prescriptions (4 DOACs and a vitamin K antagonist: VKA) in patients with non-valvular Af aged ≥65 years, taking into consideration the risk of cerebral infarction and bleeding.Methods: Anticoagulant prescriptions in outpatients with Af were temporally analyzed using the nationwide claims database in Japan. The proportion of anticoagulants prescribed to Af patients aged ≥65 years was determined. Trends in anticoagulant prescriptions were examined according to cerebral infarction and bleeding risk.Results: The proportion of anticoagulant prescriptions for 12,076 Af patients aged ≥65 years in Japan increased from 41% in 2011 to 56% in 2015. The proportion of prescriptions for DOACs surpassed that of VKA. An increase in DOAC prescriptions was accompanied by an increase in the proportion of anticoagulant prescriptions in each group according to the CHA2DS2-VASc and HAS-BLED scores. The proportion of anticoagulant prescriptions for patients with a high risk of developing cerebral infarction and bleeding showed a marked increase.Conclusion: Trends in anticoagulant prescriptions in patients with non-valvular AfAf in Japan showed a marked increase in DOAC prescriptions. The widespread use of DOACs greatly changes the profiles of cerebral infarction and bleeding risks, which are related to the prescription of anticoagulant therapy in patients with non-valvular Af.


2019 ◽  
pp. 14-19
Author(s):  
I. S. Daabul ◽  
A. A. Sokolova ◽  
I. L. Tsarev ◽  
D. A. Napalkov ◽  
V. V. Fomin

In recent years, both Russian and foreign authors have published many papers on anticoagulant therapy for atrial fibrillation (AF). The largest are devoted to the study of direct oral anticoagulants (DOACs), which have appeared in this field since 2009, and their comparison with vitamin K antagonists (VKAs) in terms of efficacy, safety and other important characteristics. There are far fewer studies on DOACs and their comparison with VKAs and with each other in patients with AF and reduced kidney function. Most of them are retrospective. Meanwhile, the prevalence of chronic kidney disease (CKD) in the population is very high, and doctors are faced with a problem of selecting anticoagulant therapy for these patients.Purpose. To assess the effect of VKAs and DOACs on renal function in real clinical practice in patients with AF depending on the stage of CKD.Materials and methods. A prospective single-centre non-randomized non-interventional observational study in parallel groups was conducted. The study included 92 patients with AF and CKD of 1-4 stages (S1-S4). The comparison group consisted of 35 patients with AF without concomitant CKD. The patients’ age ranged from 44 to 94 years (mean age was 72.2 ± 8.5 years). Patients of both groups received anticoagulant therapy with VKA (warfarin) or one of the registered in the Russian Federation DOACs (dabigatran, rivaroxaban, apixaban). During the observation (median was 10 months), follow-up visits were every 3 months. On visits we conducted the evaluation of effectiveness (strokes / TIA and thromboembolic complications) and safety (major and minor hemorrhagic events) of anticoagulant therapy, as well as the dynamics of kidney function (CC by Cockroft-Gault, GFR by CKD-EPI).Results. The main results are devoted to patients with AF and concomitant CKD. Significant dynamics of the kidney function depending on the anticoagulant taken (VKA or representatives of the DOACs class) were not identified. There were not any thromboembolic complications and major bleedings during the observation period. Statistically significant more minor bleedings on any dose of rivaroxaban in comparison with other anticoagulants were identified.Conclusions. In patients with AF and CKD, there was no significant effect of one or another anticoagulant on the kidney function, which is probably related to the concomitant nephroprotective therapy obtained in a large percentage of cases (ACE inhibitors / ARA, calcium antagonists, statins). Therapy with DOACs and warfarin in patients with AF and CKD for an average of 10 months of followup was effective and safe. In case of AF and CKD combination, the use of dabigatran or apixaban seems to be more preferable in relation to minor bleedings, the use of which less often leads to the development of hemorrhagic events. 


2019 ◽  
Vol 5 (6) ◽  
pp. 10-22
Author(s):  
O. I. Efimova ◽  
T. V. Pavlova

 This review article deals with the comparison of different modes of anticoagulant therapy, taking into account the risk profile and the individual characteristics of patients with atrial fibrillation. This paper analyzes the efficacy and safety of direct oral anticoagulants in different clinical situations. Modifiable and unmodifiable bleeding risk factors are evaluated based on the hemorrhagic complication risk assessment scales for patients taking anticoagulants. The evidence base for anticoagulant therapy in the presence of a single episode of atrial fibrillation is represented. Regimens and terms of initiation of anticoagulant therapy after a cardioembolic stroke or transient ischemic attack are considered. In addition, great attention is paid to the problem of early prescription of anticoagulants after intracranial hemorrhage. For patients at high risk of gastrointestinal bleeding or impaired renal function, an optimal strategy for reducing thromboembolic complications is evaluated. Anticoagulant therapy is also evaluated in patients with stable coronary heart disease, including after coronary stenting.


ESC CardioMed ◽  
2018 ◽  
pp. 2195-2198
Author(s):  
Margaret C. Fang

Bleeding is the primary complication associated with chronic anticoagulant treatment of atrial fibrillation and can range from minor, clinically insignificant bleeds to life-threatening events. Anticoagulants increase an individual’s bleeding risk by approximately 2–2.5-fold. The absolute rates of bleeding vary depending on the presence or absence of specific clinical risk factors, as well as the type of anticoagulant and the quality of anticoagulation management. There are many clinical risk factors for bleeding including older age, hypertension, prior bleeding, anaemia, and kidney impairment. Concomitant use of other medications, in particular other antithrombotic/antiplatelet drugs, also significantly raises bleeding risk. Intracranial haemorrhage, a relatively uncommon but widely feared complication of anticoagulants, results in a 30-day mortality of about 40%. Risk factors for intracranial haemorrhage include advanced age, elevated blood pressure, a history of cerebrovascular disease, and cerebral amyloid angiopathy. A number of risk stratification schemes have been developed in order to better estimate the risk of anticoagulant-related bleeding. Most of the risk schemes were developed and validated in patients taking vitamin K antagonists, but have increasingly been applied to populations taking the newer direct oral anticoagulants. Although bleeding risk tools can be useful to assist in counselling patients about their bleeding risk, in general, these risk schemes are only moderately predictive and are probably best applied to patients who are considered reasonable candidates for anticoagulation and who are on the lower end of ischaemic stroke risk.


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