Horizontal vs. vertical dose reduction of direct oral anticoagulants in patients with non-valvular atrial fibrillation: definition and implications for practice

2019 ◽  
Vol 62 ◽  
pp. e11-e12 ◽  
Author(s):  
Andrea Rubboli
Keyword(s):  
Atrial Fibrillation ◽  
Dose Reduction ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants

scholarly journals The role of edoxaban in preventing thromboembolic complications in patients with atrial fibrillation

2020 ◽  
pp. 28-43
Author(s):  
O. O. Shakhmatova
Keyword(s):  
Atrial Fibrillation ◽  
Drug Interactions ◽  
Dose Reduction ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Extensive Study ◽  
Thromboembolic Complications ◽  
Nonvalvular Atrial Fibrillation ◽  
Life Threatening

Edoxaban is a selective direct factor Xa inhibitor. Edoxaban in a dose of 60 mg per day is an effective and safe option in the prevention of thromboembolic complications in patients with nonvalvular atrial fibrillation, including in combination therapy in patients after percutaneous coronary interventions. ENGAGE AF-TIMI 48 is currently the most extensive study comparing direct oral anticoagulants and warfarin in patients with atrial fibrillation, both in terms of number of participants and duration of observation. For edoxaban, an adequate approach to dose reduction has been developed in patients with alikely increase in plasma concentration due to renal impairment, low body weight or inter-drug interactions. Such dose reduction does notlead to an increase in the frequency of ischemic complications.Edoxaban is characterized by an optimal safety profile in patients with chronic moderate kidney disease, a small number of drug interactions and a convenient mode of administration. In patients with atrial fibrillation and concomitant ischemic heart disease, the use of Edoxaban is associated with a decrease in the frequency of myocardial infarctions, as well as strokes and episodes of systemic thromboembolism in comparison with warfarin. The drug can be successfully used as anticoagulant support for cardioversion and catheter ablation for atrial fibrillation.Edoxaban intake does not require routinelaboratory control. In case of unexpected situations (life-threatening bleeding, urgent surgical intervention) in patients receiving edoxaban, to assess the degree of anticoagulation should use the determination of anti-Xa activity. Clinical studies of a specific antidote of edoxaban - andexanet alfa are ongoing. Before approval of the specific antidote in severe andlife-threatening bleedings against the background of edoxaban administration, the use of prothrombin complex concentrate should be considered. Data on the effective and safe use of edoxaban in routine clinical practice have been accumulated.

Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
SR Lee ◽  
EK Choi ◽  
SH Park ◽  
JH Jung ◽  
KD Han ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Dose Reduction ◽  
Standard Dose ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Off Label ◽  
Funding Sources ◽  
Asian Patients

Abstract Funding Acknowledgements Type of funding sources: None. Background In Asian patients with atrial fibrillation (AF), off-label underdosed prescriptions of direct oral anticoagulants (DOACs) are common Purpose We aimed to compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with AF. Methods Using the Korean nationwide claims database, we identified patients who prescribed apixaban and did not fulfill the dose reduction criteria of apixaban between January 2015 and December 2017. Multivariable Cox hazard regression model was performed and hazard ratios (HRs) for ischemic stroke, major bleeding (MB), all-cause death, and the composite clinical outcome were analyzed. Results Compared to patients prescribed on-label standard dose apixaban (n = 4,194), patients prescribed off-label underdosed apixaban (n = 2,890) were associated with higher risks of ischemic stroke (adjusted HR [aHR] 1.38, 95% confidence interval [CI] 1.06-1.81), all-cause death (aHR 1.19, 95% CI 1.01-1.39) and the composite clinical outcome (aHR 1.17, 95% CI 1.03-1.34), but with no significant differences in MB between the two groups (Figure). In patients without any dose reduction criteria, off-label underdosed apixaban use was associated with a significantly higher risk of ischemic stroke than on-label standard dose apixaban use (aHR 1.85, 95% 1.25-2.73); however, in patients who had single dose reduction criteria (age ≥80 years, serum creatinine ≥1.5mg/dL, or bodyweight ≤60 kg), off-label underdosed apixaban use did not show a significant overall benefit in the composite clinical outcome compared with on-label standard dose apixaban, but was associated with a higher risk of all-cause death (aHR 1.32, 95% CI 1.07-1.64). Conclusion Off-label underdosed apixaban use was associated with higher risks of ischemic stroke, all-cause death, and composite clinical outcome and comparable risk of MB compared with on-label standard dose apixaban use. Label-adherence of apixaban dosing should be emphasized to achieve the best clinical outcome for Asian patients with non-valvular AF, especially in those without any dose reduction criteria. Abstract Figure.

scholarly journals Systematic errors in the choice of dose level of direct oral anticoagulants: urgency of an issue and approaches to its solution

2021 ◽  
pp. 68-76
Author(s):  
S. R. Gilyarevskiy ◽  
N. G. Bendeliani ◽  
M. V. Golshmid ◽  
I. M. Kuzmina
Keyword(s):  
Atrial Fibrillation ◽  
Dose Reduction ◽  
Observational Studies ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Maximum Efficiency ◽  
Frequency Of Use ◽  
High Prevalence ◽  
The Relationship ◽  
Different Doses

The article presents updated information on the frequency of use of non-recommended low dosing of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban). It gives substantiation of the urgency of the issue of providing the maximum efficiency of the use of anticoagulants in clinical practice, taking into account the high prevalence of atrial fibrillation and the pharmacological characteristics of the most commonly used drugs. The effects of such an unreasonable reduction in anticoagulant doses in elderly and senile patients are discussed. The results of recent observational studies that assessed the relationship between the use of direct oral anticoagulants and the risk of adverse clinical outcomes are presented. The data on the relationship between the use of unreasonably low dosing of anticoagulants in patients with atrial fibrillation, which were recently obtained during the implementation of the GARFIELD-AF registry, are discussed. The data on a rather high variability of concentrations of direct oral anticoagulants are presented. The frequency of using apixaban in an unreasonably reduced dose, as well as the effects of using non-recommended doses of apixaban hold a specific place in the article. The unreasonableness of attempts to further reduce the risk of bleeding due to unreasonable reduction of apixaban dosing is emphasized, taking into account the stable data on the high safety of recommended dosing of apixaban, as well as the possible decrease in the effect if the dose reduction is not recommended. The data on the criteria for dose reduction, which are adopted in different countries, are presented. The proposed terms to designate different doses of direct oral anticoagulants, depending on their study in the course of large, randomized trials are discussed.

scholarly journals A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

2021 ◽  
Vol 10 (13) ◽  
pp. 2924
Author(s):  
Domenico Acanfora ◽  
Marco Matteo Ciccone ◽  
Valentina Carlomagno ◽  
Pietro Scicchitano ◽  
Chiara Acanfora ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Risk Index ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Efficacy Rate ◽  
Cochrane Central Register ◽  
Efficacy And Safety

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

scholarly journals Delayed lumbar plexus palsy due to giant psoas hematoma associated with vertebral compression fracture and direct oral anticoagulants: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chikako Ishii ◽  
Miki Komatsu ◽  
Kota Suda ◽  
Masahiko Takahata ◽  
Satoko Matsumoto Harmon ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Atrial Fibrillation ◽  
Cerebral Infarction ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Lumbar Plexus ◽  
Vertebral Compression Fractures ◽  
Minimal Risk ◽  
Motor Weakness ◽  
Segmental Artery

Abstract Background Osteoporotic vertebral compression fractures (VCFs) are commonly observed in elderly people and can be treated by conservatively with minimal risk of complications in most cases. However, utilization of direct oral anticoagulants (DOACs) increases the risks of secondary hematoma even after insignificant trauma. The use of DOACs increased over the past decade because of their approval and recommendation for both stroke prevention in non-valvular atrial fibrillation and treatment of venous thromboembolism. It is well known that DOACs are safer anticoagulants than warfarin in terms of major and nonmajor bleeding; however, we noted an increase in the number of bleeding events associated with DOACs that required medical intervention. This report describes the first case of delayed lumbar plexus palsy due to DOAC-associated psoas hematoma after VCF to draw attention to potential risk of severe complication associated with this type of common and stable trauma. Case presentation An 83-year-old man presented with his left inguinal pain and inability to ambulate after falling from standing position and was prescribed DOACs for chronic atrial fibrillation. Computed tomography angiography revealed a giant psoas hematoma arising from the ruptured segmental artery running around fractured L4 vertebra. Because of motor weakness of his lower limbs and expansion of psoas hematoma revealed by contrast computed tomography on day 8 of his hospital stay, angiography aimed for transcatheter arterial embolization was tried, but could not demonstrate any major active extravasation; therefore spontaneous hemostasis was expected with heparin replacement. On day 23 of his stay, hematoma turned to decrease, but dysarthria and motor weakness due to left side cerebral infarction occurred. His pain improved and bone healing was achieved about 2 months later from his admission, however the paralysis of the left lower limb and aftereffects of cerebral infarction remained after 1 year. Conclusion In patients using DOACs with multiple risk factors, close attention must be taken in vertebral injury even if the fracture itself is a stable-type such as VCF, because segmental artery injury may cause massive psoas hematoma followed by lumbar plexus palsy and other complications.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Obese Patients with Atrial Fibrillation

2021 ◽  
Author(s):  
Alexandros Briasoulis ◽  
Amgad Mentias ◽  
Alexander Mazur ◽  
Paulino Alvarez ◽  
Enrique C. Leira ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Comparative Effectiveness ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Obese Patients

scholarly journals Prescribing Errors With Direct Oral Anticoagulants and Their Impact on the Risk of Bleeding in Patients With Atrial Fibrillation

2021 ◽  
pp. 107424842110196
Author(s):  
Bruria Hirsh Raccah, PharmD, PhD ◽  
Yevgeni Erlichman ◽  
Arthur Pollak ◽  
Ilan Matok ◽  
Mordechai Muszkat
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Negative Impact ◽  
Conditional Logistic Regression ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Drug Dose ◽  
Prescribing Errors ◽  
Duration Of Treatment ◽  
Inappropriate Treatment

Introduction: Anticoagulants are associated with significant harm when used in error, but there are limited data on potential harm of inappropriate treatment with direct oral anticoagulants (DOACs). We conducted a matched case-control study among atrial fibrillation (AF) patients admitting the hospital with a chronic treatment with DOACs, in order to assess factors associated with the risk of major bleeding. Methods: Patient data were documented using hospital’s computerized provider order entry system. Patients identified with major bleeding were defined as cases and were matched with controls based on the duration of treatment with DOACs and number of chronic medications. Appropriateness of prescribing was assessed based on the relevant clinical guidelines. Conditional logistic regression was used to evaluate the potential impact of safety-relevant prescribing errors with DOACs on major bleeding. Results: A total number of 509 eligible admissions were detected during the study period, including 64 cases of major bleeding and 445 controls. The prevalence of prescribing errors with DOACs was 33%. Most prevalent prescribing errors with DOACs were “drug dose too low” (16%) and “non-recommended combination of drugs” (11%). Safety-relevant prescribing errors with DOACs were associated with major bleeding [adjusted odds ratio (aOR) 2.17, 95% confidence interval (CI) 1.14-4.12]. Conclusion: Prescribers should be aware of the potential negative impact of prescribing errors with DOACs and understand the importance of proper prescribing and regular follow-up.

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