Uninterrupted Direct Oral Anticoagulants Research Articles

Exploring the Perioperative Use of DOACs, off the Beaten Track

A notable increase in direct oral anticoagulant (DOAC) use has been observed in the last decade. This trend has surpassed the prescription of vitamin K antagonists (VKAs) due to the absence of the need for regular laboratory monitoring and the more favorable characteristics in terms of efficacy and safety. However, it is very common that patients on DOACs need an interventional or surgical procedure, requiring a careful evaluation and a challenging approach. Therefore, perioperative anticoagulation management of patients on DOACs represents a growing concern for clinicians. Indeed, while several surgical interventions require temporary discontinuation of DOACs, other procedures that involve a lower risk of bleeding can be conducted, maintaining a minimal or uninterrupted DOAC strategy. Therefore, a comprehensive evaluation of patient characteristics, including age, susceptibility to stroke, previous bleeding complications, concurrent medications, renal and hepatic function, and other factors, in addition to surgical considerations, is mandatory to establish the optimal discontinuation and resumption timing of DOACs. A multidisciplinary approach is required for managing perioperative anticoagulation in order to establish how to face these circumstances. This narrative review aims to provide physicians with a practical guide for DOAC perioperative management, addressing the most controversial issues.

Effect of direct oral anticoagulants on bleeding during and after cataract surgery

PurposeTo assess the risk for intraoperative and postoperative ocular bleeding associated with direct oral anticoagulant treatment in patients undergoing phacoemulsification surgery.MethodsConsecutive patients had phacoemulsification and intraocular lens implantation while taking uninterrupted direct oral anticoagulants (dabigatran, rivaroxaban, or apixaban). Gender and age-matched patients without antithrombotic therapy were used as the control group. Patients were examined one week postoperatively. Intraoperative and postoperative hemorrhagic and non-hemorrhagic complications were assessed.ResultsForty patients (56 eyes) on direct oral anticoagulants and 120 patients (172 eyes) without anticoagulation, at a mean age of 77 years, had phacoemulsification. There was no significant difference between the groups in the rate of intraoperative and postoperative bleeding. One eye (1.8%) in the treatment group and 3 eyes (1.7%) in the control group had hyphema (p = 0.72). No patient had thromboembolic event during or after surgery.ConclusionsCataract surgery was safely performed while continuing direct oral anticoagulation.

Renal function and periprocedural complications in patients undergoing left atrial catheter ablation: A comparison between uninterrupted direct oral anticoagulants and phenprocoumon administration.

Data regarding uninterrupted oral anticoagulation in patients with chronic kidney disease (CKD) during catheter ablation for left atrial arrhythmias is limited. This study aimed to evaluate the safety and efficacy of periprocedural uninterrupted direct oral anticoagulants (DOAC) compared with uninterrupted phenprocoumon in patients with CKD undergoing left atrial catheter ablation. We conducted a retrospective single-center study of patients who underwent left atrial catheter ablation between 2016 and 2019 with underlying chronic kidney disease (glomerular filtration rate (GFR) between 15 and 45ml/min). The primary objective of this study was to investigate whether direct oral anticoagulant (DOAC) therapy or warfarin presents a superior safety profile in patients with chronic kidney disease (CKD) undergoing left atrial catheter ablation. We compared periprocedural complications (arteriovenous fistula, aneurysm, significant hematoma (> 5cm)) and/or bleeding (drop in hemoglobin of >2g/dl, pericardial effusion, retroperitoneal bleeding, other bleeding, stroke) between patients receiving either uninterrupted DOAC or warfarin therapy. Secondary analysis included patient baseline characteristics as well as procedural data. A total of 188 patients (female n = 108 (57%), mean age 75.3 ± 8.1years, mean GFR 36.8 ± 6ml/min) were included in this study. Underlying arrhythmias were atrial fibrillation (n = 104, 55.3%) and atypical atrial flutter (n = 84, 44.7%). Of these, n = 132 patients (70%) were under a DOAC medication, and n = 56 (30%) were under phenprocoumon. Major groin complications including pseudoaneurysm and/or AV fistula occurred in 8.9% of patients in the phenprocoumon group vs. 11.3% of patients in the DOAC group, which was not statistically significant (p = 0.62). Incidence of cardiac tamponade (2.3% vs. 0%; p = 0.55) and stroke (0% vs. 0%) were low in both DOAC and phenprocoumon groups with similar post-procedural drops in hemoglobin levels (1.1±1g/dl vs 1.1±0.9g/dl; p= 0.71). The type of anticoagulation had no significant influence on bleeding or thromboembolic events as well as groin complications in this retrospective study. Despite observing an increased rate of groin complications, the uninterrupted use of DOAC or phenprocoumon during left atrial catheter ablation in patients with CKD appears to be feasible and effective.

Study of Modifications Induced by Continued Direct Oral Anticoagulant Therapy during Atrial Fibrillation Ablation Procedures on Standard Hemostasis Parameters

Unfractionated heparin (UFH) is used as an anticoagulant during the atrial fibrillation (AF) ablation procedure to prevent the occurrence of thromboembolic events. Guidelines recommend an activated clotting time (ACT) greater than 300 s (s) based on studies of patients treated with vitamin K antagonist (VKA) for their AF. However, direct oral anticoagulants (DOACs) have supplanted VKAs in AF and are now used as first-line therapy. It is recommended not to interrupt them during the procedure, which could interfere with the ACT measures. To assess the real-life relationship between ACT, DOAC concentrations, and UFH anti-Xa activity in patients treated by uninterrupted DOAC therapy. We conducted a single-center retrospective study. We analyzed consecutive patients with AF who underwent catheter ablation under DOAC therapy. In total, 40 patients were included, including 15 (37.5%), 20 (50.0%), and 5 (12.5%) on rivaroxaban, apixaban, and dabigatran, respectively. Baseline ACT was significantly lower in the apixaban group. ACT was linearly correlated with the residual concentration of apixaban and dabigatran but not with rivaroxaban. After UFH injection, ACT was linearly correlated with the anti-Xa activity, regardless of DOAC. Patients in the apixaban group received a higher total dose of UFH during the procedure to achieve a target ACT > 300 s, which resulted in significantly higher anti-Xa activity during the procedure. Our results raise the question of optimal management of intra-procedural heparin therapy and highlight the limitations of the ACT test, particularly in patients on apixaban.

Uninterrupted DOACs Approach for Catheter Ablation of Atrial Fibrillation: Do DOACs Levels Matter?

Most patients present for catheter ablation of atrial fibrillation (CAAF) with residual or full effect of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). In daily practice, it has been observed that the activated clotting time (ACT) was actually poorly sensitive to the effect of DOACs and that patients on DOACs required more unfractionated heparin (UFH) to achieve the ACT target of 300 s during the procedure, leading some authors to worry about potential overdosing. Conversely, we hypothesize that these higher doses of UFH are necessary to achieve adequate hemostasis during CAAF regardless of the residual effect of DOACs. During CAAF, thrombosis is promoted mainly by the presence of thrombogenic sheaths and catheters in the bloodstream. Preclinical data suggest that only high doses of DOACs are able to mitigate catheter-induced thrombin generation, whereas low dose UFH already do so. In addition, the effect of UFH seems to be lower in patients on DOACs, compared to patients on VKAs, explaining part of the differences observed in heparin requirements. Clinical studies could not identify increased bleeding risk in patients on DOACs compared to those on VKAs despite similar efficacy during CAAF procedures. Moreover, targeting a lower ACT was associated with an increased periprocedural thrombotic risk for both DOAC and VKA patients. Therefore, the low sensitivity of the ACT to the residual effect of DOACs should not be a major concern in its use in the interventional cardiology laboratory.

Optimal Anticoagulant Strategy for Periprocedural Management of Atrial Fibrillation Ablation: A Systematic Review and Network Meta-Analysis.

This network meta-analysis was performed to rank the safety and efficacy of periprocedural anticoagulant strategies in patients undergoing atrial fibrillation ablation. MEDLINE, EMBASE, CENTRAL, and Web of Science were searched to identify randomized controlled trials comparing anticoagulant regimens in patients undergoing atrial fibrillation ablation up to July 1, 2021. The primary efficacy and safety outcomes were thromboembolic and major bleeding events, respectively, and the net clinical benefit was investigated as the primary-outcome composite. Seventeen studies were included (n = 6950). The mean age ranged from 59 to 70 years; 74% of patients were men and 55% had paroxysmal atrial fibrillation. Compared with the uninterrupted vitamin-K antagonist strategy, the odds ratios for the composite of primary safety and efficacy outcomes were 0.61 (95%CI: 0.31–1.17) with uninterrupted direct oral anticoagulants, 0.63 (95%CI: 0.26–1.54) with interrupted direct oral anticoagulants, and 8.02 (95%CI: 2.35–27.45) with interrupted vitamin-K antagonists. Uninterrupted dabigatran significantly reduced the risk of the composite of primary safety and efficacy outcomes (odds ratio, 0.21; 95%CI, 0.08–0.55). Uninterrupted direct oral anticoagulants are preferred alternatives to uninterrupted vitamin-K antagonists. Interrupted direct oral anticoagulants may be feasible as alternatives. Our results support the use of uninterrupted direct oral anticoagulants as the optimal periprocedural anticoagulant strategy for patients undergoing atrial fibrillation ablation.

Effects of uninterrupted dabigatran on the intensity of anticoagulation during atrial fibrillation ablation.

BackgroundUninterrupted dabigatran during atrial fibrillation (AF) ablation is now established as the standard therapy. However, there are few reports on the effects of uninterrupted dabigatran on the intensity of anticoagulation during AF ablation.MethodsWe retrospectively analyzed 247 consecutive patients who underwent AF ablation in our hospital from January 2017 to December 2018. Patients who took warfarin or uninterrupted direct oral anticoagulants (DOACs) except for dabigatran were excluded. 89 patients underwent ablation with uninterrupted dabigatran (uninterrupted group, male 71, mean age 59.6 ± 14.0) and 124 with interrupted DOACs (interrupted group, male 105, mean age 56.9 ± 12.9) during AF ablation. The initial ACT level, proportion of ACT levels of more than 300 s, and total amount of heparin were compared. Furthermore, the incidence of procedure complications was also evaluated.ResultsThe initial ACT levels were significantly higher in the uninterrupted group, and the total number of ACTs of more than 300 s was significantly higher in the uninterrupted group (uninterrupted vs. interrupted; initial ACT level, 315.6 ± 59.8 vs. 264.5 ± 48.6, p < .001; total number of ACTs ≧300, n [%], 304/ 484 [62.8 %] vs. 372/745 [49.9%], p < .001). The total amount of heparin during procedure was significantly lower in the uninterrupted group (uninterrupted group vs. interrupted group; 12966 ± 4773 vs. 16371 ± 5212, p < .001). There was no significant difference in the incidence of complications between the two groups.ConclusionsIn the catheter ablation of AF, uninterrupted dabigatran would be useful to obtain a stable anticoagulation status during the entire procedure.

Uninterrupted Direct Oral Anticoagulants Without a Change in Regimen for Catheter Ablation for Atrial Fibrillation Is an Acceptable Protocol.

Background: In patients undergoing catheter ablation (CA) for atrial fibrillation (AF), the use of uninterrupted direct oral anticoagulants (DOACs) is the current protocol. This study evaluated bleeding complications following the uninterrupted use of 4 DOACs in patients undergoing CA for AF without any change in the dosing regimen. Moreover, we assessed differences between once- and twice-daily DOAC dosing in patients undergoing CA for AF who continued on DOACs without any change in the dosing regimen.Methods and Results: This study was a retrospective single-center cohort study of consecutive patients. All patients continued DOACs without interruption or changes to the dosing schedule, even in the case of morning procedures. The primary endpoint was the incidence of major bleeding events within the first 30 days after CA. In all, 710 consecutive patients were included in the study. Bleeding complications were less frequent in the uninterrupted twice- than once-daily DOACs group. However, the incidence of cardiac tamponade across all DOACs was low (0.98%; 7/710), suggesting that uninterrupted DOACs without changes to the dosing regimen may be an acceptable strategy. The rate of total bleeding events, including minor bleeding (12/710; 1.6%), was also satisfactory.Conclusions: Uninterrupted DOACs without any change in dosing regimen for patients undergoing CA for AF is acceptable. Bleeding complications may be less frequent in patients receiving DOACs twice rather than once daily.

Is percutaneous coronary intervention safe during uninterrupted direct oral anticoagulant therapy in patients with atrial fibrillation and acute coronary syndromes?

ObjectivesNo data on optimal management of patients with acute coronary syndromes (ACS) on long-term direct oral anticoagulants (DOACs) undergoing percutaneous coronary intervention (PCI) are available. Using the data of the...

Safety of catheter ablation of AF without pre- or periprocedural imaging for the detection of LA thrombus

Abstract Funding Acknowledgements Type of funding sources: None. Background The need for pre- or peri-procedural imaging to rule out the presence of left atrial thrombus in patients undergoing catheter ablation of atrial fibrillation (AF) is unclear in the era of uninterrupted direct oral anticoagulant (DOAC) regimen. We sought to examine the safety of catheter ablation in appropriately selected patients with paroxysmal AF without performing screening for left atrial thrombus. Methods Consecutive patients planned for radiofrequency AF catheter ablation between January 2016 and June 2020 were enrolled, and prospectively studied. All subjects were receiving uninterrupted anticoagulation with DOACs for at least 4 weeks before the procedure. All subjects were in sinus rhythm the day of the procedure. The primary outcome of the study was ischemic stroke or transient ischemic attack (TIA) during at 30 days. Results A total of 451 patients (age 59.7 ± 10.2 years, 289 males) with paroxysmal AF were included in the study. The mean CHA2DS2-VASc score was 1.4 ± 1.2. The mean left ventricular ejection fraction and left atrial diameter were 60 ± 5% and 39.3 ± 4 mm, respectively. Regarding the anticoagulation regimen, apixaban was used in 197 (43.6%) patients, rivaroxaban in 148 (32.8%) patients, and dabigatran in 106 (23.5%) patients. None of the patients developed clinical ischemic stroke or TIA during the 30-day post-discharged period. Conclusions Catheter ablation can be safely performed in low-risk patients with paroxysmal AF without imaging for the detection of left atrial thrombus in the era of uninterrupted DOAC anticoagulation.

Safety of catheter ablation of atrial fibrillation without pre- or peri-procedural imaging for the detection of left atrial thrombus in the era of uninterrupted anticoagulation.

BackgroundThe need for pre‐ or peri‐procedural imaging to rule out the presence of left atrial thrombus in patients undergoing catheter ablation of atrial fibrillation (AF) is unclear in the era of uninterrupted direct oral anticoagulant (DOAC) regimen. We sought to examine the safety of catheter ablation in appropriately selected patients with paroxysmal AF without performing screening for left atrial thrombus.Patients and MethodsConsecutive patients planned for radiofrequency AF catheter ablation between January 2016 and June 2020 were enrolled, and prospectively studied. All subjects were receiving uninterrupted anticoagulation with DOACs for at least 4 weeks before the procedure. All subjects were in sinus rhythm the day of the procedure. The primary outcome of the study was ischemic stroke or transient ischemic attack (TIA) during at 30 days.ResultsA total of 451 patients (age 59.7 ± 10.2 years, 289 males) with paroxysmal AF were included in the study. The mean CHA2DS2‐VASc score was 1.4 ± 1.2. The mean left ventricular ejection fraction and left atrial diameter were 60 ± 5% and 39.3 ± 4 mm, respectively. Regarding the anticoagulation regimen, apixaban was used in 197 (43.6%) patients, rivaroxaban in 148 (32.8%) patients, and dabigatran in 106 (23.5%) patients. None of the patients developed clinical ischemic stroke or TIA during the 30‐day post‐discharged period.ConclusionsCatheter ablation can be safely performed in low‐risk patients with paroxysmal AF without imaging for the detection of left atrial thrombus in the era of uninterrupted DOAC anticoagulation.

Abstract 13721: Is Single Dose Interruption of Direct Oral Anticoagulants Necessary Before Atrial Fibrillation Ablation? A Systematic Review and Meta-analysis

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.

Uninterrupted direct oral anticoagulants and vitamin K antagonists during ablation for atrial fibrillation: an updated meta-analysis

Abstract Background Uninterrupted anticoagulation during catheter ablation of atrial fibrillation (CAAF) became standard of care after positive results of trials investigating vitamin K antagonists (VKA). Previous studies and meta-analyses of uninterrupted direct oral anticoagulants (DOAC) vs. VKA have given controversial results. We thus aimed to elucidate the risks and benefits of uninterrupted DOAC vs. VKA during CAAF in an updated meta-analysis of randomized controlled trials (RCTs). Methods Online databases were searched for RCTs comparing uninterrupted DOAC to VKA in patients undergoing CAAF until September 2019. Data from retrieved studies were analysed in a comprehensive meta-analysis. Primary safety outcome was major bleeding; primary efficacy outcome was stroke or transient ischemic attack (TIA). Secondary outcomes included a composite of major bleeding and stroke or TIA, minor bleeding, acute cerebral lesions on magnetic resonance imaging (ACL) and mortality. Results Six eligible RCTs comprising 2,369 patients were included. Pooled meta-analysis showed no significant differences in DOAC vs. VKA concerning the rates of major bleeding (2.2% vs. 3.8%; odds ratio (OR) 0.69, 95% confidence interval (CI) 0.30–1.56; p=0.37) and stroke or TIA (0.2% vs. 0.2%; OR 0.97, CI 0.20–4.72; p=0.97). There were no significant differences found in secondary outcomes (OR 0.73, p=0.49 for composite of major bleeding and stroke or TIA; OR 1.08, p=0.52 for minor bleeding; OR 1.12, p=0.59 for ACL; and OR=0.60, p=0.64 for all-cause mortality). Conclusion Our meta-analysis suggests that uninterrupted periprocedural anticoagulation with DOAC or VKA is characterized by a similar risk/benefit ratio in patients undergoing CAAF with comparable rates of major bleeding and stroke. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical faculty of the Heinrich-Heine-University Düsseldorf, Germany

Uninterrupted twice-daily direct oral anticoagulants are safer than once-daily ones for atrial fibrillation catheter ablation

Abstract Background In patients undergoing AF catheter ablation (CA), uninterpreted DOACs reduced bleeding events without increasing ischemic events compared with vitamin K antagonist, and the continuation of anticoagulants is recommended for AF ablation. However, in the past studies, patients received once-daily DOACs in the evening, not in the morning of the procedure day. Moreover, there has been no study comparing uninterrupted 4 DOACs; therefore, the safety and effect of uninterpreted DOACs taken just in the morning of AF ablation is unknown. Objective The purpose of this study was to compare bleeding complications and thromboembolism events between 4 DOACs in patients undergoing AF ablation. Method This study was the retrospective single-center cohort study of consecutive patients who underwent AF ablation between April 2014 to July 2019. All patients continued DOAC uninterruptedly including just in the morning of the procedure. The primary endpoint included major bleeding events within the first 30 days after CA. The secondary endpoints included the composite events of ischemic stroke, systemic embolism, myocardial infarction, and vascular death. Result A total of 713 patients (mean age 64±12 years, 72% male) were included in this analysis; enrolled patients were 88, 238, 218, and 169 respectively in dabigatran, rivaroxaban, apixaban and edoxaban group. At the baseline, the ratio of age ≥75 years and CHADS2 score was higher in apixaban group, though all other baseline variables were similar between them. The primary endpoint was observed 0%, 2.1%, 0.45%, and 4.7% respectively in dabigatran, rivaroxaban, apixaban, and edoxaban group (P=0.013) without significant difference about secondary endpoint between them (P=0.3). Comparing twice-daily vs once-daily DOACs, the primary endpoint was observed significantly lower in the twice-daily group than in once-daily group (0.32% and 3.2% respectively, P=0.0054), without any significant difference about secondary endpoint (0% and 0.73% respectively, P=0.26). Conclusion Taking DOACs also in the morning of AF ablation, uninterrupted twice-daily DOACs are safer than once-daily DOACs without increasing ischemic event, although twice-daily DOACs, especially apixaban, were used in higher aged patients. Figure 1 Funding Acknowledgement Type of funding source: None

Periprocedural anticoagulation in AF cryoballoon ablation in a nationwide registry: no difference in complication rates between strategies

Abstract Background Standard treatment for patients with atrial fibrillation is pulmonary vein isolation (PVI). There are two widely adopted methods for PVI - cryoballon ablation (CBA) and radiofrequency (RF) ablation. There are several randomized studies evaluating different periprocedural anticoagulation strategies in patients undergoing PVI, and those mainly related to RF ablation procedures. However, there is a lack of data on safety of different anticoagulation strategies in CBA. Purpose To analyze the current anticoagulation approaches in patients undergoing cryoballoon ablation, the incidence and types of hemorrhagic and thromboembolic periprocedural events. The analysis was performed on data from the National cryoballoon AF ablation registry (NCT03040037). Methods Nineteen centers prospectively entered data into a web-based platform. The full data on AC therapy was available in 719 subjects. The specialists evaluated ischemic events clinically, and those included stroke, transient ischemic attack, pulmonary embolism or extracranial systemic embolism. Major bleedings were registered and classified according to the ISTH criteria. Results The mean CHA2DS2-VASc score was 2.0±1.4; mean BMI 29.5±4.8; mean GFR 92±28.9 ml/min. Periprocedurally, 574 (79.8%) subjects received direct oral anticoagulants (DOACs), 113 (15.7%) anti-vitamin K drugs (mainly warfarin); 16 (2%) patients received antiplathelet therapy. Uninterrupted DOAC therapy was used in 251 (34.9%) cases. Uninterrupted warfarin therapy was used in 36 (2%) patients. Bridging therapy was used in 325 (45.2%) patients. The total number of major adverse events was 25 (3.5%): 24 of them hemorrhagic and 1 transient ischemic attack (1 female patient on rivaroxaban with bridging). Five (0.7%) patients had hemopericardium: 3 - on uninterrupted rivaroxaban, 1 – rivaroxaban with bridging, 1 – interrupted apixaban. Seventeen (2.5%) patients had groin vascular complications and 1 -hemoptysis. Three patients died within 30 days following CBA from non-cardiovascular causes. There were no statistically significant differences in complications between patients receiving different periprocedural anticoagulation. Conclusions About 45% of patients referred for CBA receive bridging anticoagulation therapy in the periprocedural period. Although this is not in line with the current guidelines, we found no meaningful difference in complication rates between different anticoagulation approaches. CBA might be associated with different from RF ablation safety profile and requires randomized trials on periprocedural anticoagulation. Funding Acknowledgement Type of funding source: Other. Main funding source(s): RF President's council grant

Uninterrupted direct oral anticoagulant treatment during acute illness: Impact on clinical outcomes

BackgroundUninterrupted drug therapy during acute illness is often associated with pharmacokinetic and pharmacodynamic variations. Among warfarin treated patients, these changes are reflected in the INR. However, in the case of direct oral anticoagulants (DOACs), given that routine laboratory monitoring is not recommended, these changes may result in unforeseen thromboembolic or bleeding events. ObjectivesTo determine the rate of thromboembolic (TEE) and bleeding events associated with uninterrupted DOAC compared to warfarin treatment during acute illness. MethodsA retrospective cohort study of patients treated with DOACs or warfarin, both at steady state, who were hospitalized for acute illness. Primary outcome was any TEE or major bleeding requiring re-hospitalization within one month from discharge. Secondary outcome was a composite of major bleeding and clinically relevant non-major bleeding (CRNMB) events. ResultsA total of 410 patients continued oral anticoagulant treatment during their hospitalization, of whom 191 (46.6%) were on DOACs and 219 (53.4%) on warfarin, with a total of 18 (4.4%) events. Rates of TEE and major bleeding events did not differ between DOACs and warfarin treated patients (0.9% vs. 0.5% and 0.5% vs. 1%, respectively). Similarly, rate of secondary outcome was comparable between DOACs (4.7%) and warfarin (2.7%, p = 0.29). Sub-analyses demonstrated significantly higher rates among rivaroxaban (10.4%) treated patients compared to warfarin (p = 0.03). ConclusionUninterrupted treatment with DOACs during acute illness is not associated with increased risk for re-hospitalizations due to bleeding or thromboembolic events compared to warfarin. Our results suggest a higher bleeding rate among rivaroxaban treated patients at high bleeding risk.

Activated clotting time monitoring during atrial fibrillation catheter ablation: Does the anticoagulant matter?

Atrial fibrillation (AF) catheter ablation is performed in patients receiving direct oral anticoagulants (DOACs). Guidelines recommend to perform the procedure with uninterrupted anticoagulation and intra-procedural unfractionated heparin (UFH) administration to achieve activated clotting time (ACT) at 300 seconds, as recommended for vitamin K antagonist (VKA). To determine whether ACT monitoring might be transposed from VKA to DOAC-treated patients. From 124 patients receiving either uninterrupted DOAC (dabigatran, rivaroxaban, apixaban) or VKA or being untreated, blood sampling was performed for anticoagulation testing. DOAC concentrations, and INR for VKA were measured. ACT was determined at baseline, and after spiking with UFH doses equivalent to 1000, 2500, 5000 and 10000 IU in vivo. At baseline, the extent to which oral anticoagulants prolonged ACT differed: despite similar concentrations, ACT was longer with dabigatran and shorter with apixaban (both P < 0.001). The relationship between ACT and the intensity of anticoagulation also differed: ACT strongly correlated with INR ( r = 0.73, P < 0.001) and dabigatran concentration ( r = 0.87, P < 0.0001), but poorly correlated with apixaban or rivaroxaban concentrations. Moreover, the effects of UFH on ACT prolongation depended on the anticoagulant onboard: dose-response curves in samples from VKA and dabigatran-treated patients were parallel whereas ACT prolongation in response to UFH was significantly lower in the presence of FXa-inhibitors, especially apixaban. UFH administration to achieve ACT at 300 seconds may be transposed from VKA to uninterrupted dabigatran-treated patients but not to patients receiving FXa inhibitors, especially apixaban: targeting 300 seconds might expose to UFH overdosing, and bleeding complications. These findings question the indiscriminate use of ACT in AF ablation.

Uninterrupted or Minimally Interrupted Direct Oral Anticoagulant Therapy is a Safe Alternative to Vitamin K Antagonists in Patients Undergoing Catheter Ablation for Atrial Fibrillation: An Updated Meta-Analysis.

Adequate anticoagulation during catheter ablation (CA) for atrial fibrillation (AF) is crucial for the prevention of both thromboembolic events and life-threatening bleeding. The purpose of this updated meta-analysis is to compare the safety and efficacy of uninterrupted and minimally interrupted periprocedural direct oral anticoagulant (DOAC) protocols and uninterrupted vitamin K antagonist (VKA) therapy in patients undergoing CA for AF based on the latest evidence. Randomized controlled trials, prospective observational studies, and retrospective registries comparing DOACs to VKAs were identified in multiple databases (Embase, MEDLINE via PubMed, CENTRAL, and Scopus). The primary outcomes were stroke or transient ischemic attack (TIA), major bleeding, and net clinical benefit. Forty-two studies with a total of 22,715 patients were included in the final analysis. The occurrence of major bleeding was significantly lower in patients assigned to uninterrupted DOAC treatment compared to VKAs (pooled odds ratio (POR): 0.71, confidence interval (CI): 0.51–0.99). The pooled analysis of both uninterrupted and minimally interrupted DOAC groups also showed significant reduction in major bleeding events (POR: 0.70, CI: 0.53–0.93). The incidence of thromboembolic events was low, with no significant difference between groups. This updated meta-analysis showed that DOAC therapy is as effective as VKA in preventing stroke and TIA. Minimally interrupted DOAC therapy is a non-inferior periprocedural anticoagulation strategy; however, uninterrupted DOAC therapy showed superiority compared to VKA with regard to major, life-threatening bleeding. Based on our in-depth analysis, we conclude that both DOAC strategies are equally safe and preferable alternatives to VKAs in patients undergoing CA for AF.

Periprocedural and long-term safety and feasibility of direct oral anticoagulants in patients with biological valve undergoing radiofrequency catheter ablation for atrial fibrillation: a prospective multicenter study.

Direct oral anticoagulants (DOACs) are contraindicated in patients with atrial fibrillation (AF) and mechanical cardiac valves. However, safety and efficacy are controversial in patients with biological cardiac valves. We report the safety and feasibility of periprocedural and long-term treatment with DOACs in patients with biological valves undergoing ablation for AF. A total of 127 patients with AF and biological cardiac valve undergoing CA on uninterrupted DOAC were matched by gender and age with 127 patients with AF and biological cardiac valves undergoing CA on uninterrupted warfarin. All patients were anticoagulated for at least 3-4weeks prior to ablation with either rivaroxaban (70%) or apixaban (30%), which were continued for at least 3months and subsequently based on CHA2DS2-VASc score. Mean age of the study population was 63.0 ± 10.9 with 66% being male. The majority of patients on NOACs had aortic valve replacement (59%), while mitral valve was replaced in 41% of patients, which did not differ from the matched cohort on coumadin (aortic valve 57% and mitral valve 43%, (p = 0.8) (p = 0.8), respectively). The CHADS2 score was ≥ 2 in 90 patients (71.0%) on DOAC and 86 patients in (68%) the control (p = 0.6) group. Patients underwent ablation predominantly with uninterrupted rivaroxaban [89 (70%)], while the remaining 38 patients (30%) underwent ablation while on apixaban. Two groin hematomas were observed periprocedurally in both groups. No stroke/transient ischemic attack (TIA) was observed both periprocedurally and at long-term follow-up in either group. Periprocedural and long-term administration of DOACs in patients with biological cardiac valves undergoing AF ablation appears as safe as warfarin therapy.

Is transesophageal echocardiography necessary in patients undergoing ablation of atrial fibrillation on an uninterrupted direct oral anticoagulant regimen? Results from a prospective multicenter registry

Thromboembolic stroke is a rare but devastating consequence of atrial fibrillation (AF) ablation. Transesophageal echocardiography (TEE) is recommended to rule out left atrial appendage thrombus; however, its use is variable. The purpose of this study was to assess whether TEE is mandatory in patients undergoing AF ablation on uninterrupted direct oral anticoagulants (DOACs). Data from our prospective multicenter registry of patients with AF undergoing radiofrequency catheter ablation on uninterrupted DOACs were analyzed. All the included patients were on anticoagulation for at least 4 weeks before ablation. All AF ablation procedures were performed under intracardiac echocardiography guidance. Before transseptal puncture, heparin bolus was administered, followed by continuous infusion, with a target activated clotting time of >300 seconds. A total of 6186 patients (3180 on apixaban [51.4%], 2528 on rivaroxaban [40.9%], 404 on dabigatran [6.5%], and 74 on edoxaban [1.2%]) were analyzed. The mean age of the study population was 69.4 ± 10.3 years; 4194 patients (67.8%) were male, and 5120 patients (82.8%) had persistent and long-standing persistent AF. The mean CHA2DS2-VASc score was 2.86±1.58; the mean CHADS2 score was 1.65 ± 1.14. Intracardiac echocardiography ruled out left atrial appendage and left atrial thrombi in all patients and revealed "smoke" in 1672 patients (27.03%). Transient ischemic attack was noted in 1 patient with long-standing persistent AF in the setting of a missed dose of rivaroxaban before ablation. Our study showed that performing AF ablation in patients on uninterrupted DOACs without TEE is safe and feasible in high stroke risk patients. Elimination of routine preablation TEE would have significant economic and clinical implications.