scholarly journals Reasons for Switching from Warfarin to a Direct Oral Anticoagulant: A Retrospective Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5060-5060
Author(s):  
Siavash Piran ◽  
Marlene Robinson ◽  
Erjona Kruja ◽  
Sam Schulman

Abstract Background: Direct oral anticoagulants (DOACs) are slowly replacing warfarin for the prevention of stroke in atrial fibrillation and treatment and secondary prevention of venous thromboembolism. Patients with poor time in therapeutic range (TTR) are often switched to a DOAC. Poor TTR can be due to drug interactions but if the reason is poor compliance, outcomes could be worse using a DOAC without monitoring. Methods: To understand the compliance patterns we performed a retrospective chart review in patients from the anticoagulation clinic at Hamilton General Hospital that were switched from warfarin to a DOAC from April 2013 to April 2018. Patients who were taking warfarin for ≥ 2 months for any indication, except for mechanical valve prosthesis, and who were switched to a DOAC were included. We excluded patients who had a DOAC-to-DOAC switch, patients who had no reported TTR available, and those who were temporarily on warfarin after cardiac surgery. The documented reasons for a switch from warfarin to a DOAC were compared between patients with TTR ≤ 60% and >60%. Non-adherence to international normalized ratio (INR) monitoring was considered if >20% of tests were not done or delayed for more than 2 days. Results: A total of 643 eligible patients were initially screened and 288 patients were excluded: 179 had no available TTR, 93 were temporarily on warfarin after cardiac surgery, 11 were not actually switched from warfarin to a DOAC, and 5 had a DOAC-to-DOAC switch. The remaining 355 patients were included in the analysis: 223 had a TTR ≤ 60% and 132 patients had a TTR >60%. There were no differences in the median age or gender distribution. The most common indication for anticoagulation was atrial fibrillation in both groups. The median TTR was 43% in the TTR ≤ 60% group and 71% in the TTR >60% group. The median duration on anticoagulation with warfarin was significantly longer for the TTR >60% group compared with the TTR ≤ 60% group (42 months versus 19 months; P <0.001). Apixaban was the most common DOAC of choice for the switch in both groups. The most common documented reasons for a switch in the group with a TTR >60% were: switch by another physician for unknown reason (n=36), bleeding (n=30), and patient preference (n=20). The most common reasons for a switch in those with a TTR ≤ 60% were: unstable INR readings (n=42), drug interactions (n=33), and bleeding (n=30). There was no significant difference in the rate of non-adherence with the scheduled INR monitoring (42% in the group with a TTR >60% versus 49% in those with a TTR ≤ 60%). Conclusion: We found that about half of the patients on chronic anticoagulation with warfarin and switched to a DOAC were non-adherent with the scheduled INR monitoring. This, in combination with low TTR, should alert the physician of possible non-compliance with taking DOACs. Further prospective studies are needed to examine the DOAC adherence rate and clinical outcomes in this specific population. Disclosures Schulman: Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ali Hage ◽  
Daniel Dolan ◽  
Viviane G Nasr ◽  
Luis Castelo-Branco ◽  
Daniel Motta-Calderon ◽  
...  

Introduction: The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation (POAF) is limited and mostly founded on clinical trials that excluded this patient population. Hypothesis: We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with POAF. Methods: We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality, with secondary outcome of hospital readmission. We performed a random-effects meta-analysis. Results: We found 3 clinical trials, 1 prospective and 12 retrospective cohort studies eligible for inclusion with a total of 10,538 patients (3,207 DOAC patients and 7,331 warfarin patients). The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50 to 0.81, I2: 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.64, 95% CI 0.41 to 1.01, I2: 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95% CI 0.74 to 1.10, I2: 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI 0.74 to 1.37, I2: 26.5%) The secondary outcome of hospital readmission had similar risk between groups. Conclusions: Current evidence suggests that DOACs, compared to warfarin, in the management of atrial fibrillation after cardiac surgery is associated with lower risk of stroke and a strong trend for lower risk of systemic embolization, and no evidence of increased risk for hospital readmission, bleeding or mortality.


2019 ◽  
Vol 72 (6) ◽  
Author(s):  
Priscilla Shum ◽  
Gordon Klammer ◽  
Dale Toews ◽  
Arden Barry

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.   


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Poci ◽  
D Gjermeni ◽  
V Kuehlkamp

Abstract Background Catheter ablation of atrial fibrillation is known for the combining risks of thromboembolism (TE) and major bleedings. This urges a better understanding and optimization of the intraprocedural anticoagulation management. Differences in unfractionated heparin (UFH) requirements and anticoagulation time (ACT) levels between patients on different uninterrupted oral anticoagulation (OAC) agents have been studied. However, the clinical relevance, in terms of periprocedural TE and bleeding events, of UFH administration according to ACT monitoring among patients on different OAC agents, needs to be addressed. Objective To evaluate how the ACT monitoring and differences in intraprocedural UFH requirements among different anticoagulant agents, may translate to clinical outcome, in terms of periprocedural incidence of thromboembolic and bleeding events. Methods We retrospectively studied 1571 cases who underwent catheter ablation for atrial fibrillation between January 2011 and May 2017. Cases were on an uninterrupted oral OAC therapy of Vitamin K Antagonists (VKA)(713), Rivaroxaban (RG)(385), Dabigatran (DG)(260), Apixaban (AG)(192) and Edoxaban (EG)(21). First ACT measurements after the initial bolus of UFH (1ehz748.0610U), mean ACT measurements, total UFH doses/kg (Body Weight)/min (duration of procedure) and incidence of major periprocedural events were compared among the above OAC groups. Results The mean ACT (sec) was significantly lower in the AG and greater in the VKA (313,7±47 vs 340,5±49, p<0,001). Significantly lower UFH doses (U/kg/min) were required to reach the target ACT in VKA compared to RG, DG, AG and EG (0,69±0,4 vs 1,41±0,76; 1,42±0,7; 1,63±0,8; 1,37±0,4 respectively, p<0,001) The proportion of patients who achieved a target ACT value within 30 minutes after the fixed first UFH Bolus of 10 000 U was significantly lower in DG and AG compared to VKA, EG and RG group (51,5% and 49% vs 53%, 71,4%, and 61,8% respectively p=0,005). The incidence of periprocedural TE events and bleedings showed no significant difference among OAC groups. However, the 22 patients with a periprocedural TE event had significantly lower UFH doses (U)/ Duration of catheter ablation (min) compared to the ones without periprocedural TE (62,71±44,5 vs 94,4±66,4, p=0,026), despite equivalent mean ACT values between these two groups. Patients with a periprocedural TE had also a significantly older Age (69,6±10 vs 64±10 p=0,01, higher CHADSVASC Score (3,64±1,76 vs 2,63±1,7 p=0,006), longer duration of procedure (188,9±79,1 vs 144,9±57 p=0,0001) and higher pre-Ablation INR values (2,2±0,6 vs 1,7±0,6 p=0,002). Conclusions The average UFH doses required to reach the target ACT were lower in VKA than in NOAC- groups. The incidence of periprocedural TE events and bleedings was equivalent among OAC groups. Patients with TE showed a lower UFH requirement compared to no-TE group, with both groups having mean ACT ≥300 sec.


2020 ◽  
pp. 28-43
Author(s):  
O. O. Shakhmatova

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.


2020 ◽  
Vol 75 (11) ◽  
pp. 370
Author(s):  
Victor Nauffal ◽  
Ludovic Trinquart ◽  
Asishana Osho ◽  
Thoralf M. Sundt ◽  
Steven Lubitz ◽  
...  

2018 ◽  
Vol 33 (2) ◽  
pp. 136-141 ◽  
Author(s):  
Yoonsun Mo ◽  
Ayse Karakas-Torgut ◽  
Antony Q. Pham

Objective: The aim of this study is to assess patterns of potential drug–drug interactions (DDIs) with direct oral anticoagulants (DOACs) in an inpatient hospital setting. Methods: A retrospective chart review was conducted at the Brookdale University Hospital and Medical Center (BUHMC) from January 2014 to November 2016. All adult patients admitted to the BUHMC who were treated with a DOAC for at least 3 days were screened. Among them, those who received selected interacting drugs at any time during the course of DOAC therapy were included in this study. Results: This study included 165 patients with an average of 73 years (standard deviation [SD] = 12.3) and 233 cases. The most commonly used concomitant drug with a DOAC was aspirin (58%), followed by amiodarone (16%) and P2Y12 inhibitors (11%). The combined use of dual antiplatelet therapy and a DOAC was identified in 18 (6%) cases. Approximately one-third of the cases encountered were classified as the “avoidance” category. Conclusions: Despite computerized DDI alerts, potentially significant DDIs with DOACs still occur. While the present study provides insight into the current patterns of DDIs, further studies are needed to evaluate clinical outcomes of the potential DDIs with DOACs in practice.


2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 194S-201S ◽  
Author(s):  
Elias Kyriakou ◽  
Konstantinos Katogiannis ◽  
Ignatios Ikonomidis ◽  
George Giallouros ◽  
Georgios K. Nikolopoulos ◽  
...  

Our aim is to determine the most appropriate laboratory tests, besides anti-factor Xa (anti-FXa) chromogenic assays, to estimate the degree of anticoagulation with apixaban and compare it with that of rivaroxaban in real-world patients. Twenty patients with nonvalvular atrial fibrillation treated with apixaban 5 mg twice daily and 20 patients on rivaroxaban 20 mg once daily were studied. Conventional coagulation tests, thrombin generation assay (TGA), and thromboelastometry (nonactivated TEM [NATEM] assay) were performed in the 40 patients and 20 controls. The anti-FXa chromogenic assays were used to measure apixaban and rivaroxaban plasma levels. The NATEM measurements showed no significant difference between the 2 groups of patients. Concerning TGA, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban ( P < .003). A statistically significant, strong inverse correlation between apixaban plasma concentrations and ETP ( P < .001) was observed. Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban. Thrombin generation assay might provide additional information on apixaban exposure, which is required in order to individualize treatment especially for patients with a high bleeding risk. Our findings have to be further investigated in studies with larger sample sizes, in the entire range of apixaban exposure, with other direct oral anticoagulants, and in relation to clinical outcomes.


Author(s):  
Jaejin An ◽  
Zoe Bider ◽  
Tiffany Q. Luong ◽  
T. Craig Cheetham ◽  
Daniel T. Lang ◽  
...  

Background Direct oral anticoagulants (DOACs) are widely used in patients with nonvalvular atrial fibrillation for stroke prevention. However, long‐term adherence to DOACs and clinical outcomes in real‐world clinical practice is not well understood. This study evaluated long‐term medication adherence patterns to DOAC therapy and clinical outcomes in a large US integrated health care system. Methods and Results We included adult patients with nonvalvular atrial fibrillation who newly initiated DOACs between 2012 and 2018 in Kaiser Permanente Southern California. Long‐term (3.5 years) adherence trajectories to DOAC were investigated using monthly proportion of days covered and group‐based trajectory models. Factors associated with long‐term adherence trajectories were investigated. Multivariable Poisson regression analyses were used to investigate thromboembolism and major bleeding events associated with long‐term adherence trajectories. Of 18 920 patients newly initiating DOACs, we identified 3 DOAC adherence trajectories: consistently adherent (85.2%), early discontinuation within 6 months (10.6%), and gradually declining adherence (4.2%). Predictors such as lower CHA 2 DS 2 ‐VASc (0–1 versus ≥5) and previous injurious falls were associated with both early discontinuation and gradually declining adherence trajectories. Early discontinuation of DOAC therapy was associated with a higher risk of thromboembolism (rate ratio, 1.40; 95% CI, 1.05–1.86) especially after 12 months from DOAC initiation but a lower risk of major bleed compared with consistent adherence (rate ratio, 0.48; 95% CI, 0.30–0.75), specifically during the first 12 months following DOAC initiation. A gradual decline in adherence to DOACs was not statistically significantly associated with thromboembolism outcomes compared with consistent adherence. Conclusions Although a large proportion of patients with nonvalvular atrial fibrillation were adherent to DOAC therapy over 3.5 years, early discontinuation of DOAC was associated a higher risk of thromboembolic events. Future tailored interventions for early discontinuers may improve clinical outcomes.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ali H Jafry ◽  
Khawaja H Akhtar ◽  
Amna M Chaudhary ◽  
Safi U Khan ◽  
Mohammad S Khan ◽  
...  

Background: In patients with atrial fibrillation taking direct oral anticoagulants (DOACS) and undergoing catheter ablation, it is unclear if interruption of a single dose of DOAC before the procedure is necessary. We assessed the peri-procedural adverse events between uninterrupted vs single-dose interrupted DOACS. Methods: A systematic review of Medline and EMBASE was conducted and all randomized controlled trials (RCTs) and observational studies that compared uninterrupted versus interrupted DOACS were included. Random effects model was used and risk ratios (RR) with 95% confidence intervals (CI) were reported using Mantel Haenszel method. All studies defined dose interruption as holding a single dose of DOAC before ablation. Separate analyses were conducted for RCTs and observational studies. Results: Eight RCTs with 2656 patients and 4 observational studies with 834 patients were included. In RCT restricted analysis, no significant difference was seen in major bleeding [RR 0.65 (CI 0.30-1.42)], minor bleeding [RR 0.98 (0.68-1.40)], stroke/transient ischemic attack/thromboembolism [RR 0.90 (CI 0.27-2.98)] and silent cerebral infarction [RR 0.51 (CI 0.14-1.89)]. In observational study restricted analysis, no significant difference was seen in major bleeding [RR 3.04 (CI 0.13-74.07)], minor bleeding [RR 0.88 (0.46-1.69)], stroke/transient ischemic attack/thromboembolism [RR 0.98 (CI 0.12-7.91)] and a statistically significant lower silent cerebral infarction [RR 0.45 (CI 0.31-0.67)]. Conclusion: Uninterrupted DOACS are safe for patients undergoing AF ablation and logistically easier for patients. Figure 1: Forest plot showing outcomes with uninterrupted vs interrupted direct oral anticoagulants in patients undergoing ablation for atrial fibrillation in randomized controlled trials.


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