Personalized approach for direct oral anticoagulant prescription: from theory to practice

2019 ◽  
Vol 91 (7) ◽  
pp. 111-120
Author(s):  
A I Skripka ◽  
V V Kogay ◽  
A I Listratov ◽  
A A Sokolova ◽  
D A Napalkov ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Direct Oral Anticoagulant ◽  
Efficacy And Safety ◽  
Future Perspectives ◽  
Theory To Practice ◽  
Personalized Approach

Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC.

Stroke Prevention by Anticoagulants in Daily Practice Depending on Atrial Fibrillation Pattern and Clinical Risk Factors

Stroke ◽  
2021 ◽  
Author(s):  
Lamiae Grimaldi-Bensouda ◽  
Jean-Yves Le Heuzey ◽  
Jean Ferrières ◽  
Didier Leys ◽  
Jean-Marc Davy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Vitamin K ◽  
Oral Anticoagulant ◽  
Hemorrhagic Stroke ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Clinical Risk Factors ◽  
Direct Oral Anticoagulant

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50–0.98) for dabigatran, 0.68 (95% CI, 0.53–0.86) for rivaroxaban, and 0.73 (95% CI, 0.52–1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14–0.68), 0.64 (95% CI, 0.39–1.06), and 0.70 (95% CI, 0.33–1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.

scholarly journals Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of GFR among Incident and Prevalent Patients with Atrial Fibrillation

2018 ◽  
Vol 13 (8) ◽  
pp. 1144-1152 ◽  
Author(s):  
Jung-Im Shin ◽  
Alex Secora ◽  
G. Caleb Alexander ◽  
Lesley A. Inker ◽  
Josef Coresh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Oral Anticoagulant ◽  
Proportional Hazards ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Direct Oral Anticoagulant ◽  
Bleeding Events ◽  
Risk Of Bleeding

Background and objectivesAll randomized trials of direct oral anticoagulants in atrial fibrillation excluded patients with severe kidney disease. The safety and effectiveness of direct oral anticoagulants across the range of eGFR in real-world settings is unknown. Our objective is to quantify the risk of bleeding and benefit of ischemic stroke prevention for direct oral anticoagulants compared with warfarin in patients with atrial fibrillation with and without CKD.Design, setting, participants, & measurementsWe created a propensity score–matched cohort of 3206 patients with atrial fibrillation and direct oral anticoagulant use and 3206 patients with atrial fibrillation using warfarin from October of 2010 to February of 2017 in an electronic health record (Geisinger Health System). The risks of bleeding and ischemic stroke were compared between direct oral anticoagulant and warfarin users using Cox proportional hazards regression, stratified by eGFR (≥60 and <60 ml/min per 1.73 m2).ResultsThe mean (SD) age of the 6412 participants was 72 (12) years, 47% were women, and average eGFR was 69 (21) ml/min per 1.73 m2. There were 1181 bleeding events and 466 ischemic strokes over 7391 person-years of follow-up. Compared with warfarin use, the hazard ratios (HRs) (95% confidence interval [95% CI]) of bleeding associated with direct oral anticoagulant use were 1.01 (0.88 to 1.17) and 1.23 (1.02 to 1.48) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.10). There was no difference between direct oral anticoagulant and warfarin users in the risk of ischemic stroke: HRs (95% CI) of 0.94 (0.74 to 1.18) and 1.02 (0.76 to 1.37) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m2, respectively (P-interaction=0.70). Similar findings were observed with individual drugs.ConclusionsIn a large health care system, patients with eGFR<60 ml/min per 1.73 m2 who took direct oral anticoagulants for atrial fibrillation had slightly higher risk of bleeding compared with those on warfarin, but similar benefits from prevention of ischemic stroke.

scholarly journals Thrombotic events and rebleeding after hemorrhage in patients taking direct oral anticoagulants for non-valvular atrial fibrillation

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260585
Author(s):  
Daisuke Yanagisawa ◽  
Koichiro Abe ◽  
Hirohito Amano ◽  
Shogo Komatsuda ◽  
Taku Honda ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Clinical Course ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
The Other ◽  
Direct Oral Anticoagulant

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.

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.

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer – A real world experience

2018 ◽  
Vol 25 (4) ◽  
pp. 793-800 ◽  
Author(s):  
Megan K Phelps ◽  
Tracy E Wiczer ◽  
H Paige Erdeljac ◽  
Kelsey R Van Deusen ◽  
Kyle Porter ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Low Molecular Weight Heparin ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Direct Oral Anticoagulant ◽  
Recurrent Cancer ◽  
Cancer Associated Thrombosis

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry “lower risk” features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

scholarly journals Switching to Another Oral Anticoagulant and Drug Discontinuation Among Elderly Patients With Nonvalvular Atrial Fibrillation Treated With Different Direct Oral Anticoagulants

2019 ◽  
Vol 25 ◽  
pp. 107602961987024 ◽  
Author(s):  
Christine L. Baker ◽  
Amol D. Dhamane ◽  
Jigar Rajpura ◽  
Jack Mardekian ◽  
Oluwaseyi Dina ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Oral Anticoagulant ◽  
Cox Regression ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Drug Discontinuation ◽  
Research Database ◽  
Nonvalvular Atrial Fibrillation ◽  
Study Population

We compared the risks of switching to another oral anticoagulant (OAC) and discontinuation of direct oral anticoagulants (DOACs) among elderly patients with nonvalvular atrial fibrillation (NVAF) who were prescribed rivaroxaban or dabigatran versus apixaban. Patients (≥65 years of age) with NVAF prescribed DOACs (January 1, 2013 to September 30, 2017) were identified from the Humana research database and grouped into DOAC cohorts. Cox regression analyses were used to evaluate whether the risk for switching to another OAC or discontinuing index DOACs differed among cohorts. Of the study population (N = 38 250), 55.9% were prescribed apixaban (mean age: 78.6 years; 49.8% female), 37.3% rivaroxaban (mean age: 77.4 years; 46.7% female), and 6.8% dabigatran (mean age: 77.0 years; 44.0% female). Compared to patients prescribed apixaban, patients prescribed rivaroxaban (hazard ratio [HR]: 2.08; 95% confidence interval [CI], 1.92-2.25; P < .001) or dabigatran (HR: 3.74; 95% CI, 3.35-4.18, P < .001) had a significantly higher risk of switching to another OAC during the follow-up; compared to patients prescribed apixaban, the risks of discontinuation were also higher for patients treated with rivaroxaban (HR: 1.10; 95% CI, 1.07-1.13, P < .001) or dabigatran (HR: 1.29; 95% CI, 1.23-1.35, P < .001).

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

2020 ◽  
Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Efficacy And Safety

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.

scholarly journals Anticoagulant Utilization and Direct Oral Anticoagulant Prescribing in Patients with Nonvalvular Atrial Fibrillation

2019 ◽  
Vol 72 (6) ◽  
Author(s):  
Priscilla Shum ◽  
Gordon Klammer ◽  
Dale Toews ◽  
Arden Barry
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Renal Dialysis ◽  
Retrospective Chart Review ◽  
Patient Characteristics ◽  
Nonvalvular Atrial Fibrillation ◽  
Patients Âgés ◽  
Fibrillation Auriculaire

ABSTRACTBackground: Direct oral anticoagulants (DOACs) are indicated for prevention of stroke and embolism in patients with nonvalvular atrial fibrillation (NVAF). These agents have been shown to be non-inferior to warfarin in terms of efficacy and safety. However, their uptake in practice has been variable, and prescribed dosages may be inconsistent with manufacturer recommendations.Objectives: To evaluate patterns of oral anticoagulant use in patients with NVAF, including determination of patient characteristics associated with the prescribing of warfarin or DOACs and whether prescribed dosages of DOACs were concordant with manufacturer recommendations.Methods: This retrospective chart review was conducted from April to September 2017 at Abbotsford Regional Hospital, Abbotsford, British Columbia. Patients at least 18 years of age with NVAF and CHADS-65 score of 1 or higher were included. Patients with contraindications to oral anticoagulants, those with reversible atrial fibrillation, and those undergoing renal dialysis were excluded. The dosage of DOACs was categorized as too low, too high, or correct in relation to manufacturer recommendations for the Canadian product. Results: A total of 120 patients were included. At discharge, 83 (69%) of the patients had a prescription for DOAC, 25 (21%) had a prescription for warfarin, and 12 (10%) had no prescription for an oral anticoagulant. There were no statistically significant differences between the warfarin and DOAC groups with respect to patient characteristics. Among the 56 patients for whom a full DOAC dose was indicated, 7 (13%) received a dose that was too low. Among the 23 patients for whom a full DOAC dose was not indicated, 4 (17%) received a dose that was too high. Conclusions: At the study hospital, most patients with NVAF and CHADS-65 score of at least 1 had a discharge prescription for DOAC. Patient characteristics appeared to be similar between the warfarin and DOAC groups. For a notable proportion of patients who received a DOAC, the dosage was incorrect. Appropriate prescribing of oral anticoagulants could be further improved by education for prescribers and involvement of hospital pharmacists.RÉSUMÉContexte : Les anticoagulants oraux directs (AOD) sont indiqués pour prévenir les AVC et les embolies parmi les patients atteints de fibrillation auriculaire non valvulaire (FANV). Il a été démontré que l’efficacité et l’innocuité de ces agents n’étaient pas inférieures à la warfarine. Cependant, leur adoption dans la pratique est inégale, et les doses prescrites peuvent être contraires aux recommandations des fabricants.Objectifs : Évaluation des habitudes d’utilisation des anticoagulants oraux pour les patients atteints de FANV, y compris la définition des caractéristiques des patients associées à la prescription de la warfarine ou des AOD, ainsi que de la conformité des doses prescrites de ces derniers aux recommandations des fabricants.Méthodes : Cet examen rétrospectif des dossiers a été mené d’avril à septembre 2017 à l’Hôpital régional d’Abbotsford à Abbotsford, en Colombie-Britannique. Des patients âgés d’au moins 18 ans, atteints de FANV et ayant un score CHADS-65 d’au moins 1, ont été inclus dans l’étude. Les patients présentant une contre-indication aux anticoagulants oraux, ceux atteints de fibrillation auriculaire réversible et ceux soumis à une dialyse rénale en ont été exclus. La dose d’AOD destinés au marché canadien a été catégorisée comme trop faible, trop élevée ou correcte par rapport aux recommandations du fabricant.Résultats : Cent-vingt patients au total ont participé à l’étude. Au moment du congé, 83 (69 %) d’entre eux avaient une prescription d’AOD, 25 (21 %) avaient une prescription de warfarine et 12 (10 %) n’avaient pas de prescription d’anticoagulant oral. En ce qui concerne les caractéristiques des patients, il n’y avait aucune différence statistique notable entre les groupes ayant reçu une prescription de warfarine et ceux ayant reçu une prescription d’AOD. Des 56 patients qui avaient reçu une indication de dose complète d’AOD, sept (13 %) ont reçu une dose trop faible. Des 23 patients qui n’avaient pas reçu d’indication de dose complète d’AOD, quatre (17 %) ont reçu une dose trop élevée.Conclusions : À l’hôpital où s’est déroulée l’étude, la plupart des patients atteints de FANV et ceux ayant un score CHADS-65 d’au moins 1 recevaient une prescription d’AOD au moment du congé. Les caractéris-tiques des patients semblaient similaires entre les groupes ayant reçu une prescription de warfarine et ceux ayant reçu une prescription d’AOD. La dose d’AOD reçue par une proportion notable de patients était incorrecte. La prescription appropriée d’anticoagulants oraux pourrait encore être améliorée si on sensibilisait les prescripteurs avec la collaboration des pharmaciens d’hôpitaux.   

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