Management Of Direct Oral Anticoagulants Research Articles

The role of clinical pharmacy anticoagulation services in direct oral anticoagulant monitoring

The role of dedicated anticoagulation management services (AMS) for patients receiving direct oral anticoagulant (DOAC) therapy is unclear. The objective of our study was to describe DOAC management in patients who were and were not managed by an AMS. We conducted a retrospective cohort study among patients with atrial fibrillation at the University of Utah Health (UUH) who received DOAC therapy between January 2013 and June 2016. Patients in the AMS group were managed by a pharmacist-led AMS whereas those in the non-AMS group were managed by other providers. The number and type of provider encounters and interventions related to DOAC therapy and a composite endpoint of thromboembolism, bleeding, and all-cause mortality were recorded. Overall, 90 and 370 patients were managed in the AMS and non-AMS groups, respectively. AMS group patients had greater chronic disease burden as measured by the Charlson comorbidity index. AMS group patients had more frequent DOAC-related encounters than non-AMS group patients but both groups had similar DOAC therapy intervention rates. Over half of patients in the AMS group received potentially duplicative interventions from their regular clinicians. The composite endpoint occurred in 18.9% and 13.5% of AMS and non-AMS group patients, respectively (p = 0.29). Patients managed by AMS providers were more complex and had more frequent encounters regarding their DOAC therapy than those managed by non-AMS providers. However, there was evidence of duplicative DOAC therapy management efforts. No difference between AMS and non-AMS groups in the composite clinical endpoint was detected.

Dental extractions on direct oral anticoagulants vs. warfarin: The DENTST study

BackgroundConflicting recommendations exist addressing the management of direct oral anticoagulants (DOACs) for invasive dental procedures. ObjectivesTo determine the safety of DOAC continuation compared to warfarin continuation for dental extractions with regards to bleeding outcomes. MethodsA single‐center, prospective, cohort study was performed to compare 7‐day bleeding outcomes between patients who continued their DOAC, and patients on warfarin with an International Normalized Ratio (INR) between 2.0 and 4.0. Blood tests including oral anticoagulant drug levels were measured immediately prior to extraction. The gauze used to apply pressure to the socket was weighed before and after extraction to estimate blood loss. Patients were contacted by phone 2 and 7 days after extraction. ResultsEighty‐six patients on a DOAC had a total of 145 teeth extracted, and 21 patients on warfarin had 50 teeth extracted. There were no major bleeding events. The rate of minor plus clinically relevant nonmajor bleeding was comparable between the DOAC and warfarin cohorts (36% and 43%, respectively; odds ratio, 0.75; 95% confidence interval, 0.29‐1.98). Preextraction apixaban and dabigatran levels were comparable between bleeders and nonbleeders, while rivaroxaban levels were higher in those who bled. The weight change of gauze used to tamponade the socket was similar between the 2 cohorts. ConclusionDental extractions on patients continuing DOACs led to bleeding rates similar to patients on warfarin with an INR between 2.0 and 4.0. There is no need to adjust DOAC dosing prior to dental extractions.

The Peri-Operative Management of Anticoagulants: Systemic Review of Guidelines

Introduction Venous thromboembolism (VTE) and atrial fibrillation are thrombotic disorders resulting in significant morbidity and mortality, if left untreated. In Canada, 45,000 people, or 1-2 cases per 1000 people, per year will experience an acute VTE, and it is estimated that 200,000 Canadians have atrial fibrillation. The treatment of VTE and atrial fibrillation often includes the use of anticoagulants. Patients on anticoagulation may need interruption of treatment for surgeries and procedures. To evaluate differences in perioperative anticoagulation management strategies we conducted a systematic review of the peri-operative clinical practice guidelines for anticoagulants. Methods A protocol using the Preferred Reporting Items for Systematic review and Meta-analysis Protocols (PRISMA-P) was developed. Relevant primary clinical practice guidelines were identified using MEDLINE, EMBASE, and guideline-specific databases. All guidelines from the preceding 20 years up to January 11, 2019 were screened. Eligible manuscripts were reviewed by two independent reviewers. Data abstraction was independently completed in duplicate for included guidances and categorized according to thrombotic risks and bleeding risks. Guidances on emergency surgeries were not included for the purposes of this review. Information on anticoagulation interruption, bridging regimens, laboratory testing, and reversal strategies were collected. Results Eight guidelines met inclusion criteria and 6 contained sufficient information for peri-operative management of anticoagulants. One guideline focused on patients presenting with bleeding events and restated the same peri-operative guidelines as had been published a year prior by the same group, and was excluded. Another guideline only addressed emergency surgeries and was also excluded from this review. The majority of the guidelines had similar definitions of risk factors for venous and arterial thrombotic events (see table 1). There were no conflicting guidance recommendations identified, but there were differences in the component of peri-operative management addressed by each guideline, ie bridging, reversal agents, laboratory tests. The levels of evidence used to develop recommendations varied between guidelines. All guidelines provided recommendations on warfarin and low molecular weight heparins (LMWH) management and only one guideline provided suggestions for direct oral anticoagulants (DOACs). The findings for perioperative anticoagulation management for patients with atrial fibrillation and VTE are presented in Tables 2 and 3, respectively. For high bleeding risk surgeries, most guidelines cited similar studies resulting in similar recommendations for interruption of warfarin and bridging in high venous and arterial thrombotic risk patients. In high bleeding risk procedures and low thrombotic risk patients, no bridging is recommended. For low bleed risk procedures, regardless of thrombotic risk, guidelines recommended for continuation of anticoagulant therapy. Discussion This systematic review identified 6 guidelines of non-urgent peri-operative management recommendations of primarily warfarin and LMWH in patients with VTE and atrial fibrillation. While no major discrepancies in the guideline suggestions were noted, the scope of data examined (medication management, bridging, blood tests, reversal of agents) differed amongst the various agencies. The guidelines that were most consistent for recommendations of anticoagulant management and bridging tended to be from hematologic societies. The only guideline that addressed perioperative management of DOACs was the 2018 ASH guideline on management of VTE which was against measurement of DOAC levels prior to procedures. The lack of thorough guidance for DOACs is likely due to the year of publication of the guidelines examined and paucity of contributing studies. In terms of reversal agents, all clinical practice guidelines except for the ASH guidelines were prior to specific DOAC reversal agents such as idaracizumab. Future Directions We anticipate that there will be other guidelines developed that address specifically the use of DOACs in the perioperative setting, as well as their reversal agents. Disclosures Shivji: BMS-Pfizer Thrombosis Canada: Other: Fellowship award. Castellucci:BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Sanofi: Honoraria; Aspen: Honoraria; Servier: Honoraria.

Management of Direct Oral Anticoagulants in Patients with Atrial Fibrillation Undergoing Cardioversion.

Atrial fibrillation the most common cardiac arrhythmia. Its incidence rises steadily with each decade, becoming a real “epidemic phenomenon”. Cardioversion is defined as a rhythm control strategy which, if successful, restores normal sinus rhythm. This, whether obtained with synchronized shock or with drugs, involves a periprocedural risk of stroke and systemic embolism which is reduced by adequate anticoagulant therapy in the weeks before or by the exclusion of left atrial thrombi. Direct oral anticoagulants are safe, manageable, and provide rapid onset of oral anticoagulation; they are an important alternative to heparin/warfarin from all points of view, with a considerable reduction in bleedings and increase in the safety and quality of life of patients.

Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant

Patients with atrial fibrillation (AF) who use a direct oral anticoagulant (DOAC) and request elective surgery or procedure present a common clinical situation yet perioperative management is uncertain. To investigate the safety of a standardized perioperative DOAC management strategy. The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) cohort study conducted at 23 clinical centers in Canada, the United States, and Europe enrolled and screened patients from August 1, 2014, through July 31, 2018. Participants (n = 3007) had AF; were 18 years of age or older; were long-term users of apixaban, dabigatran etexilate, or rivaroxaban; were scheduled for an elective surgery or procedure; and could adhere to the DOAC therapy interruption protocol. A simple standardized perioperative DOAC therapy interruption and resumption strategy based on DOAC pharmacokinetic properties, procedure-associated bleeding risk, and creatinine clearance levels. The DOAC regimens were omitted for 1 day before a low-bleeding-risk procedure and 2 days before a high-bleeding-risk procedure. The DOAC regimens were resumed 1 day after a low-bleeding-risk procedure and 2 to 3 days after a high-bleeding-risk procedure. Follow-up of patients occurred for 30 days after the operation. Major bleeding and arterial thromboembolism (ischemic stroke, systemic embolism, and transient ischemic attack) and the proportion of patients with an undetectable or minimal residual anticoagulant level (<50 ng/mL) at the time of the procedure. The 3007 patients with AF (mean [SD] age of 72.5 [9.39] years; 1988 men [66.1%]) comprised 1257 (41.8%) in the apixaban cohort, 668 (22.2%) in the dabigatran cohort, and 1082 (36.0%) in the rivaroxaban cohort; 1007 patients (33.5%) had a high-bleeding-risk procedure. The 30-day postoperative rate of major bleeding was 1.35% (95% CI, 0%-2.00%) in the apixaban cohort, 0.90% (95% CI, 0%-1.73%) in the dabigatran cohort, and 1.85% (95% CI, 0%-2.65%) in the rivaroxaban cohort. The rate of arterial thromboembolism was 0.16% (95% CI, 0%-0.48%) in the apixaban cohort, 0.60% (95% CI, 0%-1.33%) in the dabigatran cohort, and 0.37% (95% CI, 0%-0.82%) in the rivaroxaban cohort. In patients with a high-bleeding-risk procedure, the rates of major bleeding were 2.96% (95% CI, 0%-4.68%) in the apixaban cohort and 2.95% (95% CI, 0%-4.76%) in the rivaroxaban cohort. In this study, patients with AF who had DOAC therapy interruption for elective surgery or procedure, a perioperative management strategy without heparin bridging or coagulation function testing was associated with low rates of major bleeding and arterial thromboembolism.

Appropriateness of Direct Oral Anticoagulant Dosing in Patients With Atrial Fibrillation: Insights From the Veterans Health Administration

Background: Direct oral anticoagulants (DOACs) have strict dosing guidelines, but recent studies indicate that inappropriate dosing is common, particularly in chronic kidney disease (CKD), for which it has been reported to be as high as 43%. Since 2011, the Veterans Health Administration (VA) has implemented anticoagulation management programs for DOACs, generally led by pharmacists, which has previously been shown to improve medication adherence. Objective: We investigated the prevalence of overdosing and underdosing of DOACs in the VA. Methods: Using data from the TREAT-AF cohort study (The Retrospective Evaluation and Assessment of Therapies in AF), we identified VA patients with newly diagnosed atrial fibrillation (AF) and receipt of a DOAC between 2003 and 2015. We classified dosing as correct, overdosed, or underdosed based on the Food and Drug Administration–approved dosing criteria. Results: Of 230 762 patients, 5060 received dabigatran (77.3%) or rivaroxaban (22.7%) within 90 days of AF diagnosis (age 69 [10[ years; CHA2DS2-VASc 1.6 [1.4]), of which 1312 (25.9%) had CKD based on estimated glomerular filtration rate <60. Overall, 93.6% of patients, 83.2% with CKD, received appropriate DOAC dosing. Incorrect dosing increased with worsening renal function. Conclusion: Compared to recent studies of commercial payers and health-care systems, incorrect dosing of DOACs is less common across the VA. Pharmacist-led DOAC management or similar anticoagulation management interventions may reduce the risk of incorrect dosing across health-care systems.

Perioperative management of direct oral anticoagulants in patients undergoing radical prostatectomy: results of a prospective assessment.

In the perioperative setting, temporary interruption of direct oral anticoagulants (DOACs) is recommended. However, the safety of these recommendations is based on non-urological surgical experiences. Our objective was to verify the safety of these recommendations in patients undergoing radical prostatectomy (RP). Patients regularly receiving a DOAC and scheduled for RP at our institution were prospectively assessed. DOAC intake was usually stopped 48h before surgery without any preoperative bridging therapy. Postoperatively, patients received risk-adapted low-molecular weight heparin (LMWH). On the third day after unremarkable RP, DOAC intake was restarted and the administration of LMWH was stopped. We assessed perioperative outcomes and 30-day morbidity. Thirty-two consecutive patients receiving DOAC underwent RP at our institution between 12/2017 and 07/2018. Time of surgery (median, 177min) and intraoperative blood loss (median, 500mL) were unremarkable. DOACs were restarted on the third postoperative day in 30 patients (94%). No patient had a significant hemoglobin level reduction after DOAC restart. Overall, 28% of patients experienced complications within 30days after surgery. Most of which were minor (Clavien ≤ 2), three patients (9%), however, had Clavien ≥ 3 complications. Our report is the first to prospectively assess current guideline recommendations regarding DOAC restarting after major urological surgery. RP can safely be performed, if DOACs are correctly paused before surgery. Moreover, in case of an uneventful postoperative clinical course, DOACs can be safely restarted on the third postoperative day. A 9% Clavien ≥ 3 30-day morbidity warrants attention and should be further explored in future studies.

Management strategies of the interaction between direct oral anticoagulant and drug-metabolizing enzyme inducers.

Little is known regarding the management of direct oral anticoagulants (DOACs) in patients with enzyme-inducing drugs (EID). The use of EID may lead to sub-therapeutic concentrations of DOACs and to treatment failure. Thus, many patients on EIDs cannot benefit from the advantages of DOACs. This was a retrospective study, evaluating the management of hospitalized patients with DOACs. Characteristics of hospitalized patients with a prescription for DOACs, with and without EIDs, were summarized and evaluated, and management strategies addressing the potential interaction were documented, including the use of DOAC concentration monitoring. During the period evaluated, 1596 hospitalized patients with prescriptions for DOACs were identified. Most patients received apixaban (n = 1227, 77%), followed by rivaroxaban (240, 15%), and dabigatran (129, 8%). Twenty-two patients (1.4%) had concomitant EIDs. Demographic and clinical characteristics of hospitalized patients with DOACs were similar in those receiving EID and those not. Management strategies included stopping DOAC or EID (41%), and DOAC dose increase (14%). During management of these interactions, DOAC concentrations were measured for 11 of 22 patients and were below the 5th percentile of expected concentration for six of these patients. The management of patients with DOAC concentration measurement differed significantly from those without (p = 0.005), as they were much less likely to have one of the medications stopped and more often had the DOACs' dose increased. Among hospitalized patients with DOACs, EIDs are not rare. DOAC concentrations are often low in the presence of EIDs. DOAC concentration monitoring may be useful in settings requiring both DOAC and EIDs.

Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study: A Perioperative Management Plan for Patients with Atrial Fibrillation Who Are Receiving a Direct Oral Anticoagulant

Introduction: The perioperative management of patients who are taking a direct oral anticoagulant (DOAC) for atrial fibrillation (AF) and require an elective surgery/procedure is uncertain. No studies have addressed the timing of perioperative DOAC interruption and resumption, and if perioperative heparin bridging and coagulation function testing are needed. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study hypothesized that a simple, standardized perioperative management strategy, based on DOAC-specific interruption and resumption intervals, that foregoes perioperative heparin bridging and coagulation function testing, is safe for patient care, with associated low rates of major bleeding (1%) and arterial thromboembolism (0.5%). We postulated that this management yields a high proportion of patients (>90%) with a minimal to no DOAC level at surgery/procedure. Methods: PAUSE is a prospective study with 3 parallel DOAC cohorts of patients with AF taking apixaban, dabigatran or rivaroxaban and requiring anticoagulant interruption for an elective surgery/procedure. Patients were managed using a standardized protocol based on DOAC pharmacokinetic properties, procedure-associated bleeding risk (Appendix 1) and creatinine clearance (CrCl). DOACs were interrupted for 1 day before and after surgery for a low bleed risk surgery and 2 days before and after a high bleed surgery; longer interruption was done in patients on dabigatran with a CrCl Results: We enrolled 3007 patients from 23 sites in Canada, the U.S. and Europe (Appendix 4). The patient characteristics were (Figure 2): mean age 72.5 years; 66.1% male; 33.5% high bleeding risk surgery/procedure, with 1257 patients in the apixaban cohort, 668 in the dabigatran cohort and 1082 in the rivaroxaban cohort (Table 1). DOAC interruption and resumption intervals are shown in Table 2. The 30-day postoperative rate (95% CI) of major bleeding was 1.35% (0-2.00) in the apixaban cohort, 0.90% (0-1.73) in the dabigatran cohort and 1.85% (0-2.65) in the rivaroxaban cohort; the rate (95% CI) of arterial thromboembolism was 0.16% (0-0.48) in the apixaban cohort, 0.6% (0-1.33) in the dabigatran cohort and 0.37% (0-0.82) in the rivaroxaban cohort (Table 3). There were 2541 (84.5%) patients with preoperative DOAC levels measured: a level Conclusions: In patients with AF who were taking a DOAC (apixaban, dabigatran, rivaroxaban) and required anticoagulant interruption for an elective surgery/procedure, using a standardized DOAC-specific perioperative management strategy was safe for patient care, with associated low rates of perioperative MB ( 90% overall; 98.8% at high bleeding risk) had a minimal or no residual DOAC level at the time of the surgery/procedure. PAUSE is the largest study, to date, that addresses how to manage the common problem of perioperative DOAC management. It is likely to have a practice-changing impact and will inform future practice guidelines in perioperative care. Study Funding: CIHR (313156) and the H&S Foundation of Canada (G-14-0006136). Aniara-Hyphen Biomed (assays). Acknowledgements: We thank Drs. Walter Ageno, David Garcia, Lehana Thabane, Wendt Lim, Lori Linkins, William Ristevski, and Demetrios J. Sahlas. Also, Kayla Lucier, Grace Wang, Tara McDougall, and HRLMP and CRLB. Supported by CanVector and REDCap. Disclosures Douketis:Bayer: Other: Advisory Board; Janssen: Consultancy; BMS: Other: Advisory Board; Biotie: Other: Advisory Board; Daiichi-Sankyo: Other: Advisory Board; Boehringer-Ingelheim: Consultancy, Other: Advisory Board, Research Funding; The Medicines Company: Other: Advisory Board; Sanofi: Consultancy, Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Portola: Other: Advisory Board; Pfizer: Other: Advisory Board. Spyropoulos:Janssen Scientific Affairs, LLC: Consultancy. Carrier:Bayer: Honoraria; Leo Pharma: Research Funding; Pfizer: Honoraria; BMS: Honoraria, Research Funding. Vanassche:Bayer: Consultancy; Boehringer Ingelheim: Consultancy; BMS/Pfizer: Consultancy. Verhamme:Bayer: Honoraria, Research Funding; Medtronic: Honoraria; Portola: Honoraria; Boehringer Ingelheim: Honoraria; Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Shivakumar:Pfizer: Honoraria; Servier: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria. Gross:Pfizer: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Servier: Honoraria. Lee:Pfizer: Consultancy, Research Funding; BMS: Research Funding; Servier: Honoraria; LEO Pharma: Consultancy, Research Funding; Bayer: Consultancy, Honoraria. Le Templier:BMS-pfizer: Honoraria. Wu:Leo Pharma: Honoraria; Pfizer: Honoraria; BMS-Pfizer: Honoraria. Coppens:Bayer: Honoraria, Other: Non-financial support, Research Funding; CSL Behring: Honoraria, Other: non-financial support, Research Funding; Uniqure BV: Research Funding. Arnold:Bristol Myers Squibb: Research Funding; UCB: Consultancy; Amgen: Consultancy, Research Funding; UCB: Consultancy; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Research Funding. Caprini:Alexion Pharmaceuticals: Membership on an entity9s Board of Directors or advisory committees; Recovery Force: Consultancy; BMS: Membership on an entity9s Board of Directors or advisory committees; Pfizor: Membership on an entity9s Board of Directors or advisory committees; Janssen RD Bayer: Honoraria; Sanofi: Honoraria; Boehringer-Ingelheim: Honoraria, Research Funding.

Direct oral anticoagulants: a review of common medication errors.

Stroke and venous thromboembolism continues to be a major cause of morbidity and mortality worldwide. The use of anticoagulation therapy has proven effective in the prevention of stroke and management of thromboembolism; however, initiating treatment may bear clinical burden given the capacity of these agents to cause bleeding. Originally, warfarin has been primarily used, but with the approval of direct oral anticoagulants, therapeutic recommendations have shifted to direct oral anticoagulants for first line therapy for venous thromboembolism for patients without cancer. As compared to warfarin, direct oral anticoagulants are associated with predictable pharmacokinetic profiles, lower bleeding risks, and minimal drug interactions. Complexities in the medication use process can however heighten the risks of causing adverse events. The purpose of this article is to describe common medication errors associated with direct oral anticoagulants, provide practical guidance on the management of direct oral anticoagulants, and suggest strategies to reduce errors. Efforts to minimize medication errors involve the participation of an interdisciplinary team that has standardized policies, risk reduction strategies, and guiding principles to achieve optimal therapeutic outcomes. Current primary literature is not robust in assessment of clinical impact of medication errors associated with DOACs but reports of adverse drug events have been noted. Future studies should be guided to assess clinical outcomes associated with medication errors and identify potential clinical interventions to optimize therapy.

International consensus statement on the peri-operative management of direct oral anticoagulants in cardiac surgery.

Despite current recommendations on the management of severe peri-operative bleeding, there is no pragmatic guidance for the peri-operative monitoring and management of cardiac surgical patients taking direct oral anticoagulants. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology, of their own volition, performed an independent systematic review of peer-reviewed original research, review articles and case reports and developed the following consensus statement. This has been endorsed by the European Association of Cardiothoracic Anaesthesiology. In our opinion, most patients on direct oral anticoagulant therapy presenting for elective cardiac surgery can be safely managed in the peri-operative period if the following conditions are fulfilled: direct oral anticoagulants have been discontinued two days before cardiac surgery, corresponding to five elimination half-live periods; in patients with renal or hepatic impairment or a high risk of bleeding, a pre-operative plasma level of direct oral anticoagulants has been determined and found to be below 30 ng.ml-1 (currently only valid for dabigatran, rivaroxaban and apixaban). In cases where plasma level monitoring is not possible (e.g. assay was not available), discontinuation for 10 elimination half-live periods (four days) is required. For FXa inhibitors, a standard heparin-calibrated anti-Xa level of < 0.1 IU.ml-1 should be measured, indicating sufficient reduction in the anticoagulant effect. Finally, short-term bridging with heparin is not required in the pre-operative period.

Periendoscopic management of direct oral anticoagulants: a prospective cohort study

ObjectiveTo assess the frequency of adverse events associated with periendoscopic management of direct oral anticoagulants (DOACs) in patients undergoing elective GI endoscopy and the efficacy and safety of the British...

Direct oral anticoagulants: When to consider laboratory testing?

Direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic stroke, as well as for prevention and treatment of venous thromboembolism. Dose adjustment based on laboratory testing is not required; however, there are several potential situations that deserve insight into a DOAC plasma activity level. Based on a series of real-life case descriptions, we discuss indications for dedicated DOAC testing, as well as the interpretation and consequences. Testing of DOACs in selected patients may help to better interpret acute situations such as bleeding or thrombosis while on anticoagulation, but also suspected drug failure, drug accumulation, or lack of adherence. The 24/7 availability of target-specific tests with adequate calibration is recommended to support the clinician in the interpretation and where needed adjustment of the management of patients on DOACs. The relevance of laboratory-guided DOAC management, particularly in the elderly, merits further study.

Periprocedural Management of Direct Oral Anticoagulants Surrounding Cardioversion and Invasive Electrophysiological Procedures.

As direct oral anticoagulants (DOACs) have demonstrated favorable efficacy and safety outcomes compared with vitamin K antagonists for the treatment and prevention of venous thromboembolism and the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, their role in the management of anticoagulation during electrophysiological procedures continues to evolve. At present, guidelines are limited regarding specific recommendations for the use of DOACs in these clinical settings. Here, we review available data regarding the risks and benefits associated with various periprocedural anticoagulation management approaches when patients receiving DOACs undergo electrophysiologic procedures including cardioversion, ablation, and device implantation. This discussion is intended to provide clinicians with an overview of available evidence and best practices to minimize the risk of both thromboembolic and bleeding events in the periprocedural setting.

Expanding anticoagulation management services to include direct oral anticoagulants.

Despite the ease of use of direct oral anticoagulants (DOACs), these agents remain high risk medications and their clinical efficacy can be impacted by factors such as patient adherence, drug procurement barriers, bleeding leading to discontinuation, and prescribing that deviates from approved dosing regimens. Clinical monitoring of patients on DOACs should be performed by clinicians who specialize in anticoagulation and are familiar with the nuances of DOAC dosing, monitoring, and other components of anticoagulation management including peri-procedural management and care transitions. Although data for centralized warfarin management have consistently demonstrated improved clinical outcomes compared to traditional management by individual community providers, there are no published data addressing the impact of centralized management of DOACs on clinical outcomes or anticoagulation control. In addition, there is currently no consensus on how to incorporate patients on DOACs into this centralized model, despite recommendations for systematic follow-up by both the Anticoagulation Forum and the Institute for Safe Medication Practices. Based on the national recommendations and an identified institutional need, the Brigham and Women's Hospital Anticoagulation Management Service implemented a pilot program to expand services to include patients newly initiated on, or transitioned to, a DOAC. We describe our model for expansion of the AMS to include patients on DOACs.

Decision Algorithms for Direct Oral Anticoagulant Use in Patients With Nonvalvular Atrial Fibrillation: A Practical Guide for Neurologists.

Direct oral anticoagulants (DOACs) are valid alternative options to vitamin K antagonists due to their limited interactions with drugs or food and the fact that they do not require regular coagulation monitoring. To this regard, recent practice guidelines recommend that DOACs should be considered as first-line anticoagulant therapy for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). This review (1) outlines current international guidelines for the management of DOACs to prevent stroke in patients with NVAF, (2) outlines indications for elderly patients as well as specific settings including acute coronary syndromes and intracranial hemorrhage, and (3) offers a practical guide for the use of DOACs in neurological settings.

Incorporating Comprehensive Management of Direct Oral Anticoagulants into Anticoagulation Clinics.

Anticoagulation clinics emerged as a means to optimize warfarin effectiveness and minimize bleeding risks. Anticoagulation clinics have traditionally been warfarin-based models due to the need for frequent blood-level monitoring, drug interactions, dietary considerations, and periprocedural management with warfarin. These models have demonstrated improved anticoagulation control and reduced bleeding complications for patients taking warfarin. Direct oral anticoagulants (DOACs) emerged with the perception of improved convenience due to the lack of blood-level monitoring and lack of dietary considerations. Despite the advantages of DOAC therapy, new challenges exist with their management, warranting ongoing monitoring. Such challenges include prescribing and dosing issues, drug adherence, drug interactions, and high drug cost. Comprehensive anticoagulation centers are needed to manage and monitor all oral anticoagulants including DOACs. The objectives of this review are to describe the challenges and opportunities that exist in the management of DOACs and to describe a practice model that integrates a DOAC management service into the traditional anticoagulation clinic.

Sa1032 Appropriate and Safe Management of Direct Oral Anticoagulants in Endoscopic Resection of Colorectal Polyps

Sa1032 Appropriate and Safe Management of Direct Oral Anticoagulants in Endoscopic Resection of Colorectal Polyps

Managing the perioperative patient on direct oral anticoagulants.

Patients are increasingly treated with direct oral anticoagulants (DOACs) for the prevention of stroke due to non-valvular atrial fibrillation and for the treatment of venous thromboembolism. When these patients present for urgent or emergent surgical procedures, they present a challenge to the anesthesiologist who must manage perioperative risk due to anticoagulation. The purpose of this module is to review the literature surrounding the perioperative management of DOACs. Timing, laboratory monitoring, and availability of reversal agents are important considerations to optimize patients being treated with DOACs who require emergent surgery. Laboratory tests are not recommended for routine monitoring of DOACs since they do not correlate well with anticoagulant activity. Most widely available laboratory tests lack the sensitivity to detect anticoagulant effects at low plasma concentrations. However, a normal thrombin time for dabigatran excludes clinically significant drug levels. If the risk of bleeding is judged to be high because of a recent dose of DOAC, various options are available to mitigate bleeding. When possible, surgery should be delayed for at least 12 hr after the last dose of DOAC. Activated charcoal may mitigate the anticoagulant effect caused by DOACs if administered less than two hours after the drug was ingested. Four-factor prothrombin complex concentrates (PCCs) may be useful to reduce life-threatening bleeding associated with factor Xa inhibitors. Activated PCCs have been shown to reverse abnormal coagulation tests associated with all DOACs, but there is a lack of reported evidence of clinical benefit. Idarucizumab is a specific antidote that is effective for reversal of anticoagulation due to dabigatran. An antidote for rivaroxaban and apixaban (andexanet alfa) as well as a universal antidote for all DOACs and heparin (PER977) are in clinical development. Perioperative management of anticoagulation due to DOACs is a growing concern as the number of patients prescribed these medications increases each year. These patients can be safely optimized for urgent or emergent surgery by giving appropriate consideration to timing, monitoring, and reversal agents.

Utilization and prescribing patterns of direct oral anticoagulants

BackgroundScant literature exists evaluating utilization patterns for direct oral anticoagulants (DOACs).ObjectivesThe primary objective was to assess DOAC prescribing in patients with venous thromboembolism (VTE) and nonvalvular atrial fibrillation (NVAF) in outpatient clinics. Secondary objectives were to compare utilization between family medicine (FM) and internal medicine (IM) clinics, characterize potentially inappropriate use, and identify factors associated with adverse events (AEs).MethodsThis was a retrospective cohort study of adults with NVAF or VTE who received a DOAC at FM or IM clinics between 10/19/2010 and 10/23/2014. Descriptive statistics were utilized for the primary aim. Fisher’s exact test was used to evaluate differences in prescribing using an adapted medication appropriateness index. Logistic regression evaluated factors associated with inappropriate use and AEs.ResultsOne-hundred twenty patients were evaluated. At least 1 inappropriate criterion was met in 72 patients (60.0%). The most frequent inappropriate criteria were dosage (33.0%), duration of therapy (18.4%), and correct administration (18.0%). Apixaban was dosed inappropriately most frequently. There was no difference in dosing appropriateness between FM and IM clinics. The odds of inappropriate choice were lower with apixaban compared to other DOACs (odds ratio [OR]=0.088; 95% confidence interval [CI] 0.008–0.964; p=0.047). Twenty-seven patients (22.5%) experienced an AE while on a DOAC, and the odds of bleeding doubled with each inappropriate criterion met (OR=1.949; 95% CI 1.190–3.190; p=0.008).ConclusionPotentially inappropriate prescribing of DOACs is frequent with the most common errors being dosing, administration, and duration of therapy. These results underscore the importance of prescriber education regarding the appropriate use and management of DOACs.