DOACs- balance between thrombosis and bleeding - A Review

Bleeding is a common side effect of anticoagulant use. However, the majority of bleeding events are not life-threatening and can be managed conservatively. The first step in managing any significant bleeding event is to temporarily stop using the anticoagulant. The aim of this review was to determine the appropriate management strategy for an acutely bleeding patient on DOACs. Direct oral anticoagulants (DOACs) are now widely used in treatment of venous thromboembolism (VTE) and are recommended first-line over vitamin K antagonists (VKAs) in non-cancer associated VTE. Until recently, supportive measures and infusion of clotting factors were the only available options for reversal of DOACs. Within the last 4 years, approval of specific antidotes has led to hopes for improved outcomes in DOAC-related acute bleeding, however limitations remain including cost, availability and "real-world" data. In severe and life-threatening bleeding events, use of non-specific (e.g. PCC) or specific (e.g. idarucizumab, andexanet alpha) reversal agents are recommended. However, further data is needed to compare outcomes between these two management strategies and identify the cost-effectiveness of these various strategies.

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Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

Critical Care Research and Practice ◽

10.1155/2018/4907164 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Alok Dabi ◽

Aristides P. Koutrouvelis

Keyword(s):

Side Effects ◽

Intracranial Hemorrhage ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Coagulation Cascade ◽

Reversal Agents ◽

United States Food ◽

Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

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Use of Direct Oral Anticoagulants in Patients with Sickle Cell Disease and Venous Thromboembolism Is Associated with a Significant Decrease in Incidence of Bleeding Compared to Vitamin K Antagonists and Low-Molecular-Weight Heparins

Blood ◽

10.1182/blood.v130.suppl_1.978.978 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 978-978

Author(s):

Ameet Patel ◽

Hants Williams ◽

Maria R. Baer ◽

Ann Butler Zimrin ◽

Jennie Y Law

Keyword(s):

Molecular Weight ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Event ◽

Low Molecular Weight ◽

Inclusion Criteria ◽

Cell Disease ◽

Bleeding Events ◽

Bleeding Rate

Abstract Background: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD). Several studies confirm that SCD itself is an independent risk factor for development of VTE. However, the optimal pharmacologic anticoagulant remains unknown. Methods: This retrospective single-institution cohort study was exempt by the Institutional Review Board. Data were collected via review of electronic medical records including ambulatory, emergency department, general floor, and intensive care unit encounters. Patients with SCD were identified spanning 1/2009-7/2017 using ICD 9/10 codes. Inclusion criteria were age ≥18 years at time of VTE diagnosis, imaging confirming VTE, and documented compliance based on INR values and/or provider/pharmacy documentation. VTE diagnosis included deep vein thrombosis (DVT) at any location and pulmonary embolism based on documented imaging and ICD 9/10 codes. Anticoagulants included direct oral anticoagulants (DOACs), vitamin K antagonists (VKA), and low-molecular-weight heparin (LMWH). The DOACs used in this study were rivaroxaban, apixaban and dabigatran. Exclusion criteria were known active malignancy, confirmed hypercoagulable risk factors beyond SCD, atrial fibrillation and/or history of major bleeding prior to anticoagulation. Due to low event rates, a log likelihood ratio test of independence was calculated for associations between drug type and two endpoints: bleeding rate and rate of VTE recurrence. Rate of VTE recurrence was defined as a newly diagnosed VTE within 6 months of initiation of anticoagulation. Bleeding rate was defined using International Society on Thrombosis and Hemostasis criteria: bleeding event into a critical site and/or a ≥2 point decrease in baseline hemoglobin. Results: A total of 109 patients with SCD met inclusion criteria. 66 patients (60%) were female. SCD genotypes represented included HbSS in 91 patients (83%), HbSC in 12 (11%) and HbS β+ thalassemia in 4 (4%). There were no patients with HbS-β0 thalassemia. VTEs consisted of 69 DVTs and 43 pulmonary emboli. 31 out of 109 VTEs were provoked, including 30 catheter-related incidents. After initial VTE event, 32 patients received a VKA, 34 received LMWH, and 43 received a DOAC. Within the class of DOACs, 31 patients received rivaroxaban, 5 received apixaban, and 7 received dabigatran. Sixteen of 109 patients (15%) experienced a clinically significant bleeding event, including 8 on VKA, 6 on LMWH, and 2 on a DOAC. Bleeding incidence was least with the DOAC class [0.22 CI (0.04-0.84) p < 0.05], greatest with warfarin [1.55 CI (0.57-4.33) p < 0.05] and slightly less with LMWH [0.64 CI (0.23-1.73) p < 0.05]. There was a significant decrease in incidence of bleeding events in patients receiving a DOAC for anticoagulation, compared to a VKA or LMWH (p = 0.033). At a median follow-up of 11.8 months (range, 3.4 - 60 months), 33 patients had a recurrent VTE, including 10 on VKA, 10 on LMWH and 13 taking a DOAC (p = 0.833). An association between VTE and SCD genotype could not be identified due to small numbers of patients with non-HbSS genotypes. Conclusion: In patients with SCD and VTE, there was a significant decrease in incidence of bleeding events in patients receiving a DOAC for anticoagulation, compared to a VKA or LMWH (p = 0.033). There was no difference between VTE recurrence rate and choice of initial anticoagulation. Figure Figure. Disclosures No relevant conflicts of interest to declare.

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Direct oral anticoagulants (DOAC) – Management of emergency situations

Hämostaseologie ◽

10.5482/hamo-16-11-0043 ◽

2017 ◽

Vol 37 (04) ◽

pp. 257-266 ◽

Cited By ~ 3

Author(s):

Edelgard Lindhoff-Last

Keyword(s):

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Real Life ◽

Bleeding Complications ◽

Severe Bleeding ◽

Emergency Operations ◽

Reversal Agents ◽

Life Threatening

SummaryThe worldwide increase in the aging population and the associated increase in the prevalence of atrial fibrillation and venous thromboembolism as well as the widespread use of direct oral anticoagulants (DOAC) have resulted in an increase of the need for the management of bleeding complications and emergency operations in frail, elderly patients, in clinical practice. When severe bleeding occurs, general assessment should include evaluation of the bleeding site, onset and severity of bleeding, renal function, and concurrent medications with focus on anti-platelet drugs and nonsteroidal anti-inflammatory drugs (NSAID). The last intake of the DOAC and its residual concentration are also relevant. The site of bleeding should be immediately localized, anticoagulation should be interrupted, and local measures to stop bleeding should be taken. In life-threatening bleeding or emergency operations immediate reversal of the antithrombotic effect may be indicated. If relevant residual DOAC-concentrations are expected and surgery cannot be postponed, prothrombin complex concentrate (PCC) and/or a specific antidote should be given. While idarucizumab, the specific antidote for dabigatran, has been recently approved for clinical use, the recombinant factor X protein andexanet alfa, an antidote for the reversal of inhibitors of coagulation factor Xa, and ciraparantag, a universal antidote, are not available. Future cohort studies are necessary to assess the efficacy and safety of specific and unspecific reversal agents in “real-life” conditions. This was the rationale for introducing the RADOA-registry (RADOA: Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists), a prospective non-interventional registry, which will evaluate the effects of specific and unspecific reversal agents in patients with life-threatening bleeding or emergency operations either treated with DOACs or vitamin K antagonists.

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Andexanet alfa for reversal of factor Xa inhibitors: a critical review of the evidence

Future Cardiology ◽

10.2217/fca-2019-0038 ◽

2019 ◽

Vol 15 (6) ◽

pp. 395-404

Author(s):

Jameel Abdulrehman ◽

John W Eikelboom ◽

Deborah M Siegal

Keyword(s):

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Activity Levels ◽

Reversal Agents ◽

Life Threatening ◽

Andexanet Alfa ◽

Anticoagulated Patients

Direct oral anticoagulants are associated with lower rates of bleeding than vitamin K antagonists, but life-threatening bleeding still occurs. Andexanet alfa is a catalytically inactive recombinant modified human factor Xa molecule that reverses the anticoagulant effect of direct and indirect acting factor Xa inhibitors. In the ANNEXA-4 study, treatment with andexanet was associated with a 92% reduction in median anti-Xa activity levels and excellent or good hemostasis in 82% of patients presenting with serious bleeding while receiving apixaban or rivaroxaban. In this review, we discuss the burden of bleeding in anticoagulated patients and the need for reversal agents, review the mechanism of action of andexanet and critically evaluate the evidence for its efficacy and safety.

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A Review on the Use of Reversal Agents of Direct Oral Anticogulant Drugs in Case of Gastrointestinal Bleeding

Reviews on Recent Clinical Trials ◽

10.2174/1574887115666200624193938 ◽

2020 ◽

Vol 15 ◽

Author(s):

Veronica Ojetti ◽

Angela Saviano ◽

Mattia Brigida ◽

Luisa Saviano ◽

Alessio Migneco ◽

...

Keyword(s):

Gastrointestinal Bleeding ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Medical Emergency ◽

Management Approach ◽

Emergency Setting ◽

Reversal Agents ◽

Life Threatening ◽

Andexanet Alfa

Background : Major bleeding is a life-threatening condition and a medical emergency with high mortality risk. It is often the complication of anticoagulant’s intake. Anticoagulants are commonly used for the prevention and the treatment of thrombotic events. The standard therapy with vitamin K antagonist (warfarin) has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban, edoxaban, dabigatran, betrixaban) showed a better efficacy and safety compared to standard warfarin treatment and they are recommended for the reduction of ischemic stroke. Literature data reported a high risk of gastrointestinal bleeding with DOACs, in particular with dabigatran and rivaroxaban. In case of life-threatening gastrointestinal bleeding, these patients could benefit from the use of reversal agents. Methods: We performed an electronic search on PUBMED of the literature concerning reversal agents for DOACs and gastrointestinal bleeding in the Emergency Department from 2004 to 2020. AIM: This review summarizes the current evidences about three reversal agents idarucizumab, andexanet alfa and ciraparantag, and the use of the first two in the emergency setting in patients with an active major bleeding or who need urgent surgery to offer physicians indications for a better management approach in order to increase patient’s safety. Conclusion: Although these agents have been marketed for five years (idarucizumab) and two years (andexanet alfa) respectively, and despite guidelines considering antidotes as first-line agents in treating life-threatening hemorrhage when available, these antidotes seem to gain access very slowly in the clinical practice. Cost, logistical aspects and need for plasma level determination of DOAC for an accurate therapeutic use probably have an impact on this phenomenon.. An expert multidisciplinary bleeding team should be established so as to implement international guidelines based on local resources and organization.

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In-Hospital Mortality and Morbidity Among Patients Presenting with Intracranial Hemorrhage: A Single Center's Experience with Vitamin K Antagonists and the Direct Oral Anticoagulants

Blood ◽

10.1182/blood-2019-131769 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3668-3668

Author(s):

Christopher Cipkar ◽

Sujitha Srinathan ◽

Philip Chiang ◽

Lana A Castellucci

Keyword(s):

Hospital Mortality ◽

Chart Review ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Event ◽

Mortality Rates ◽

Clinical Impact ◽

Mortality And Morbidity ◽

Ottawa Hospital

Background Oral anticoagulants are the preferred therapy for the treatment of venous thromboembolism and for stroke prevention among patients with atrial fibrillation. Given their widespread use, clinicians must balance efficacy of anticoagulation with their associated bleeding risks. Specifically, intracranial hemorrhage (ICH) is the most feared complication as this form of bleeding has the highest mortality and morbidity. To date, clinical trials suggest a lower incidence of ICH and better safety profile among patients prescribed the direct oral anticoagulants (DOACs) compared with traditional vitamin k antagonists (VKAs). Although promising, further understanding is needed to appreciate the clinical impact once a DOAC-related bleeding event does occur. The aim of this study was to evaluate anticoagulation use, in-hospital mortality rates and functional outcome among patients presenting with ICH to a large tertiary care center in Canada. Methods In this study, we present data from a retrospective chart review of patients who presented to The Ottawa Hospital with ICH between January 2016 and December 2017. Patients were identified using ICD-10 codes from the Ottawa Hospital Data Warehouse. Patient demographics, type of anticoagulant/antiplatelet agent and indication for therapy were collected. The primary outcome was in-hospital mortality rates among patients prescribed oral anticoagulants compared with those not anticoagulated or on antiplatelet therapy. A secondary outcome was functional assessment of survivors at hospital discharge using the modified Rankin Scale (mRS), a validated tool used widely in contemporary stroke research to measure the degree of disability after a neurological event. Results 481 patients were identified in the Data Warehouse and manual chart review confirmed 429 patients diagnosed with ICH. Patients not taking any anticoagulant or antiplatelet therapy tended to be younger and had lengthier admissions with longer stays in the ICU. The most common indication for anticoagulation in those presenting with ICH was atrial fibrillation. Intraparenchymal bleeding was most common among patients on DOACs, while patients on warfarin tended to have more subdural hematomas (Table 1). In-hospital mortality was 45.8% in DOAC-related ICH, 29.4% in warfarin-related ICH and 15.5% in patients not on an anticoagulant or antiplatelet. Average modified Rankin Scale at the time of discharge was 4.52 in DOAC-related ICH, 4.23 in warfarin-related ICH and 3.2 in patients not on an anticoagulant or antiplatelet (Table 2). Conclusions In this cohort of patients presenting with ICH to a large academic hospital, the in-hospital mortality rate was higher in patients receiving oral anticoagulation compared to those not on anticoagulants. DOAC-related ICH tended to have worse outcomes with higher in-hospital mortality and worse functional outcomes among survivors on discharge. Although the DOACs are reported in the literature to have an overall lower incidence of ICH, further information is still needed to understand the clinical impact when a bleeding event does occur. Disclosures Castellucci: BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Sanofi: Honoraria; Aspen: Honoraria; Servier: Honoraria.

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Safety and timing of resuming dabigatran after major gastrointestinal bleeding reversed by idarucizumab

SAGE Open Medical Case Reports ◽

10.1177/2050313x17753336 ◽

2018 ◽

Vol 6 ◽

pp. 2050313X1775333 ◽

Cited By ~ 1

Author(s):

Gian Galeazzo Riario Sforza ◽

Francesco Gentile ◽

Fabio Stock ◽

Francesco Caggiano ◽

Enrica Chiocca ◽

...

Keyword(s):

Atrial Fibrillation ◽

Case Report ◽

Major Bleeding ◽

Acute Treatment ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Oral Vitamin ◽

Bleeding Events ◽

Massive Rectal Bleeding

The recent introduction of direct oral anticoagulants, including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism and in atrial fibrillation has been shown to provide greater clinical benefit than oral vitamin K antagonists. However, direct oral anticoagulants are associated with adverse events, the most common being major bleeding; such events require the reversal of the anticoagulant effects by specific agents. In this case report, we describe an 87-year-old female with atrial fibrillation treated with dabigatran who had massive rectal bleeding. Idarucizumab 5 g (2 × 2.5 g/50 mL) was successfully used to reverse dabigatran effect; subsequent to this, treatment with dabigatran was resumed, and there were no further bleeding events. This suggests that dabigatran can be safely restarted after major bleeding, but this outcome needs to be confirmed in studies involving larger groups of patients.

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Abstract MP38: Intracerebral Hemorrhage Across the United States: Incidence and Mortality Trends From 1990 to 2017

Stroke ◽

10.1161/str.52.suppl_1.mp38 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Augustin DeLago ◽

Harpreet Singh ◽

Arashdeep Rupal ◽

Chinmay Jani ◽

Arshi Parvez ◽

...

Keyword(s):

United States ◽

Intracerebral Hemorrhage ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

The United States ◽

Mortality Trends ◽

Reversal Agents ◽

Incidence And Mortality ◽

The Us

Background: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variation remain unknown; especially after a dramatic increase in the use of direct oral anticoagulants (DOACs) since 2010. Our study reports updated incidence, mortality and mortality to incidence ratio (MIR) data related to ICH across the US. Methods: This observational study utilized the Global Burden of Disease database to determine age-standardized incidence (ASIR), death (ASDR) and MIR rates for ICH overall and for each state in the US from 1990-2017. All analyses were stratified by sex. Trends were analyzed using Joinpoint regression analysis, with presentation of estimated annual percentage changes (EAPCs) in ASIRs, ASDRs and MIRs over the observation period. Results: We observed an overall decrease in ASIRs, ASDRs and MIRs in both genders from 1990-2017, apart from female ASIRs and ASDRs in West Virginia and Kentucky. In 2017, the mean ASIR per 100,000 population for men was 25.67 and 19.17 for women. The 2017 mean ASDRs per 100,000 population for men and women were 13.96 and 11.35, respectively. The District of Columbia had the greatest decreases in ASIR EAPCs for males at -41.25% and females at -40.58%, and the greatest decreases in ASDR EAPCs for both males and females at -55.38% and -48.51%, respectively. The overall MIR during the study period decreased in males by -12.12% and females by -7.43%. However, MIR increased in males from 2014-2017 (EAPC +2.2% [95% CI +0.9%-+3.5%]) and in females from 2011-2017 (EAPC +1.0% [CI +0.7%-+1.4%]). Conclusion: This report reveals overall decreasing trends in incidence, mortality and MIR from 1990-2017. Notably, no significant change in mortality was found in the last 6 years of the study period, and MIR worsened in males from 2014-2017 and in females from 2011-2017, suggesting decreased ICH related survival lately. The substitution of vitamin K antagonists with DOACs is one possible explanation for a downtrend in incidence despite an aging population and increased use of anticoagulants. Limited access to reversal agents for DOACs is a potential reason for increase in MIR, however concrete deductions cannot be made owing to the observational nature of the study.

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P690Incidence of events between vitamin K antagonists and direct oral anticoagulants in patients with cancer

European Heart Journal ◽

10.1093/eurheartj/ehz747.0295 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Pardo Sanz ◽

L M Rincon ◽

G De Lara ◽

A Tamayo ◽

L C Belarte ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Systemic Embolism ◽

Bleeding Events ◽

Patients With Cancer

Abstract Background Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We aimed to evaluate the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with breast cancer. We also compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. Methods It is an ambispective observational multicentric study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain in the period 2011–2018. A total of 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. The incidence of thromboembolic and major bleeding events according to the antithrombotic strategy with VKAs or DOACs was evaluated in the cohort of 637 patients with cancer. Analysis were conducted using SPSS software V.22.0 and R V.3.5.1, with a two-tailed significance value of 0.05. Results Mean follow-up was 3.1 years. Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. There was no evidence that the incidence of ischemic stroke/systemic embolism differed between patients with cancer treated with AVK and DOAC after CHA2DS2-VASc adjustment: HR 0.91 (95% CI, 0.42–1.99). In addition, no significant differences in the incidence of major bleeding events were found between DOACs and VKA after adjustment for HAS-BLED score: HR 1.53 (95% CI, 0.93–2.53) (Figure 3). Gastrointestinal bleeding was the main source of haemorrhages in both groups (45% of bleedings among patients treated with DOACs and, 37% in VKAs group). Metastatic disease or active chemotherapy were studied as potential covariates but none of them posed any relevant change in the result. Kaplan-Meier analysis Conclusions Cancer patients treated with DOACs did not differ versus those treated with VKAs with regards to stroke or systemic embolism in a model adjusted for CHA2DS2-VASc. Neither significant differences were found for bleeding events in a model adjusted for baseline HASBLED.

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P1860Unfractionated heparin dose and complication rate in catheter ablation of atrial fibrillation, a comparison between uninterrupted therapy with phenprocoumon and direct oral anticoagulants

European Heart Journal ◽

10.1093/eurheartj/ehz748.0610 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

N Poci ◽

D Gjermeni ◽

V Kuehlkamp

Keyword(s):

Atrial Fibrillation ◽

Catheter Ablation ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Events ◽

Anticoagulation Management ◽

Significant Difference ◽

The Mean ◽

Initial Bolus

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.

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