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 ◽  
...  

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.

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.


2021 ◽  
Vol 10 (35) ◽  
pp. 3047-3052
Author(s):  
Pavithra M ◽  
Arvind Muthukrishnan

The incidence of thromboembolic diseases is high. It is one of the leading causes of death and disability. Anticoagulants are used for preventing or reducing blood clot formation and treatment of other related thrombotic disorders. Vitamin K antagonists (VKA) were developed more than 60 years ago. Warfarin is the most commonly used VKA. The drawbacks of vitamin K antagonists were that it requires frequent monitoring and dose adjustments, food and drug interactions, narrow therapeutic range, diet restrictions. For the past 15 years, various new drugs have been introduced to overcome the disadvantages of vitamin K antagonists. In 2008, a new group of anticoagulants were introduced. They are known as novel anticoagulants (NOAC) or direct oral anticoagulants. They include dabigatran, apixaban, rivaroxaban and edoxaban. The major issue with NOAC is difficulty in monitoring the dose. A literature search was done on this topic. It is very important for the dentists to know the bleeding complications in patients under anticoagulant therapy. The dental treatment of patients who tend to have an increased risk of bleeding due to the use of anticoagulants and / or antiplatelet drugs raises a challenge in the daily practice of dental professionals. According to current evidence, there is no significant difference in postoperative bleeding between novel anticoagulants and vitamin K antagonists. The risk of thromboembolic events on stopping the anticoagulants should be assessed. Local haemostatic measures are shown to suffice to control possible bleeding secondary to dental treatments. KEY WORDS Anticoagulants; Apixaban; Dabigatran; Dentistry; Edoxaban; Rivaroxaban.


Author(s):  
Martin Müller ◽  
Ioannis Chanias ◽  
Michael Nagler ◽  
Aristomenis K. Exadaktylos ◽  
Thomas C. Sauter

Abstract Background Falls from standing are common in the elderly and are associated with a significant risk of bleeding. We have compared the proportional incidence of bleeding complications in patients on either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA). Methods Our retrospective cohort study compared elderly patients (≥65 years) on DOAC or VKA oral anticoagulation who presented at the study site – a Swiss university emergency department (ED) – between 01.06.2012 and 01.07.2017 after a fall. The outcomes were the proportional incidence of any bleeding complication and its components (e.g. intracranial haemorrhage), as well as procedural and clinical parameters (length of hospital stay, admission to intensive care unit, in-hospital-mortality). Uni- and multivariable analyses were used to compare the studied outcomes. Results In total, 1447 anticoagulated patients were included – on either VKA (n = 1021) or DOAC (n = 426). There were relatively more bleeding complications in the VKA group (n = 237, 23.2%) than in the DOAC group (n = 69, 16.2%, p = 0.003). The difference persisted in multivariable analysis with 0.7-fold (95% CI: 0.5–0.9, p = 0.014) lower odds for patients under DOAC than under VKA for presenting with any bleeding complications, and 0.6-fold (95% 0.4–0.9, p = 0.013) lower odds for presenting with intracranial haemorrhage. There were no significant differences in the other studied outcomes. Conclusions Among elderly, anticoagulated patients who had fallen from standing, those under DOACs had a lower proportional incidence of bleeding complications in general and an even lower incidence of intracranial haemorrhage than in patients under VKAs.


2015 ◽  
Vol 4 (1) ◽  
pp. 44 ◽  
Author(s):  
Philipp Bushoven ◽  
Sven Linzbach ◽  
Mate Vamos ◽  
Stefan H Hohnloser ◽  
◽  
...  

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.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Emma Kirstine Laugesen ◽  
Laila Staerk ◽  
Nicholas Carlson ◽  
Anne-Lise Kamper ◽  
Jonas Bjerring Olesen ◽  
...  

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.


Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  

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.


2020 ◽  
Vol 145 (14) ◽  
pp. 978-986
Author(s):  
Harald Darius

AbstractThe number of patients with atrial fibrillation (AF) is increasing due to the aging of the population. In addition, the number of patients with AF and an indication for oral anticoagulation (OAC) for the prevention of strokes increases, who are in need for a dual antiplatelet therapy (DAPT) with acetyl salicylic acid (ASA) plus a P2Y12-Inhibitor because of an acute coronary syndrome and/or coronary stent implantation. These patients did receive a triple therapy (TT) for 3–12 months in the past. Triple therapy never has been studied for efficacy or safety, however, the rate of bleeding complications in comparison to OAC or DAPT is significantly higher.Registries and smaller trials showed that dual therapy with an OAC plus a single platelet inhibitor may be sufficient to prevent strokes and stent thromboses/myocardial infarctions. Four prospective randomized trials involving all four NOACs (Non-Vitamin K oral anticoagulants) approved for stroke prevention in AF have been undertaken. The NOACs plus one antiplatelet agent were tested versus vitamin K-antagonists plus DAPT. In the meantime, the trials involving rivaroxaban (PIONEER AF-PCI), dabigatran (RE-DUAL PCI), apixaban (AUGUSTUS), and edoxaban (ENTRUST-AF-PCI) have been published. The current status is that a NOAC plus a single antiplatelet agent, mostly clopidogrel, is superior to TT with respect to the bleeding complications, without any obvious and statistically significant disadvantage for stroke rates or cardiac ischemic events. The international guidelines already recommend to treat with a NOAC and one antiplatelet agent instead of TT in case the patients bleeding risk is prevailing. Thus, TT seems not to be indicated anymore for most patients with AF and ACS or PCI.


2016 ◽  
Vol 115 (03) ◽  
pp. 562-569 ◽  
Author(s):  
Joerg Kreuzer ◽  
Martina Brueckmann ◽  
Friedrich Schulze ◽  
Karl-Heinz Liesenfeld ◽  
Andreas Clemens

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.


2015 ◽  
Vol 114 (11) ◽  
pp. 1076-1084 ◽  
Author(s):  
Franziska Michalski ◽  
Luise Tittl ◽  
Sebastian Werth ◽  
Ulrike Hänsel ◽  
Sven Pannach ◽  
...  

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.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Binding ◽  
J.B Olesen ◽  
C Lee ◽  
C Sindet-Petersen ◽  
C.T Pedersen ◽  
...  

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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