What Are the Optimal Anticoagulation Strategies Before, During, and After Catheter Ablation of Atrial Fibrillation?
論文ID: CJ-22-0516
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論文ID: CJ-22-0516
Catheter ablation (CA) is a widely accepted therapy for atrial fibrillation (AF). One of the clinical interests in this field is the management of periprocedural and post-CA oral anticoagulant (OAC) therapy. Studies have reported that uninterrupted therapy with direct OACs (DOACs) reduces thromboembolic risks,1,2 but OAC therapy may also increase the risk of procedural bleeding complications. According to the current guidelines and consensus statements, continuation of OACs without interruption is Class I/IIa, and withholding 1–2 DOAC doses before CA is also Class IIa.3–5 It remains unclear whether interrupted or minimally interrupted OAC therapy is ideal for periprocedural OAC management. Also, it is still controversial when and in whom OAC therapy can be discontinued after CA because the risk and benefit balance of OAC therapy needs to be considered.
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In this issue of the Journal, Nogami et al6 highlight these unresolved issues of anticoagulation management for periprocedural and remote period outcomes after CA of AF using data from a prospective large-scale multicenter Japanese observational study. Of their total study patients (n=3,072), most (92.6%) received DOACs, 5.1% had warfarin and 2.3% had no OACs. In the DOAC group, 82.3% received minimally interrupted DOAC therapy and only 10.2% had uninterrupted DOACs.6 In a 2018 German study, ≈90% of registered centers used some type of interrupted DOAC therapy.7 Despite the guidelines recommending uninterrupted DOAC therapy, these reports indicated that the incidence of interrupted DOAC therapy is very high before CA in real-world settings. It is possibly because the operators fear the potential for major bleeding events and/or the small time period between the publication of the abovementioned guidelines and when the patients were entered into those studies. Therefore, the occurrence of interrupted DOAC therapy might gradually decrease in the near future, as the enlightenment campaign spreads. One important finding in their study was that during the periprocedural period, the number of thromboembolic events was extremely low, regardless of DOAC or warfarin therapy (0.2% and 0.6%, respectively), but major bleeding events occurred in 4.5% with DOACs and 3.8% with warfarin. Female sex, long-standing persistent AF, creatinine clearance <67 mL/min, hepatic disorder, no antiarrhythmic drug use, and total intraprocedural heparin dose ≥12,000 IU were independently associated with periprocedural major bleeding, but intervals of <12 h, 12 to <24 h, and ≥24 h between the last DOAC administration and the first puncture for CA (D‒A interval) were not. Importantly, the former 4 variables are well-known patient factors for a bleeding risk, whereas the last one (i.e., total intraprocedural heparin dose) is a modifiable risk. The intraprocedural heparin requirement was significantly higher in the DOAC subgroup with a D‒A interval ≥12 h than in the DOAC subgroup with a D‒A interval <12 h (P<0.0001). Therefore, despite having a longer period of interrupted DOAC therapy to avoid bleeding events, the resulting heparin dose may have increased, thus increasing bleeding events. This suggests that higher intraprocedural heparin doses due to a D‒A interval ≥12 h and/or a long procedure should be avoided, especially in patients with a high risk of bleeding as stated above.
Regarding OAC management during the remote period after CA in their study, 1 year after CA the OAC therapy had continued in over half of the patients regardless of DOAC or warfarin administration. Even in patients with a low risk of thromboembolisms, the DOAC continuation rate was not low (37.5% for CHADS2=0 and 53.5% for CHADS2=1). Under that OAC status, the incidence of thromboembolic events was very low (0.3%), and 0% in the warfarin group. They emphasize that a clinical issue of OAC management in the remote period after CA was major bleeding, the incidence of which was significantly higher in the warfarin group (3.99%) than in the DOAC group (1.14%; P=0.0021). These data reflect the focus of physicians on thromboembolic risks rather than bleeding risks in the real-world setting, possibly because many studies and guidelines have stated that careful decision-making for the cessation of OAC therapy in the remote period after CA should be done while considering the patients’ risk and post-AF recurrence including asymptomatic AF recurrence undetected by standard ECG monitoring devices.3,5,8,9 Nogami et al6 identified age ≥73 years, dementia, and AF recurrence as independent factors for major bleeding events. Univariate analysis revealed that continuation of warfarin therapy and off-label overdoses of DOACs were risk factors for major bleeding during the remote period. Therefore, off-label DOAC overdosing should at least be avoided. Taking these results together with those of prior studies,10,11 they state that the serious bleeding risk associated with OACs appears to outweigh the benefits of thromboembolism reduction and conclude that for patients with a low risk of a stroke, discontinuation of OAC therapy is recommended.6 Nonetheless, their statement should be carefully interpreted because there is a potential to increase stroke events if OACs are discontinued even in patients with a low risk of stroke. In addition, when understanding the balance between the risks and benefits of OAC therapy, the outcomes of strokes and major bleeding, such as disability or death, should be considered. This study had no information regarding fatal bleeding and stroke-related deaths, but it remains unclear whether bleeding events really outweigh thromboembolic events when considering a 0.3% of thromboembolic event rate and 1.14% of major bleeding events in the DOAC group.6 Nevertheless, warfarin-related major bleeding events were higher, reaching up to 3.99%, so if patients are to be given warfarin after CA, DOACs may be a preferable option. Despite considerable limitations specific to real-world data, they report few adverse events during the periprocedural DOAC therapy and acceptable 1-year clinical outcomes under a relatively high rate of DOAC continuation during the remote period after CA in a Japanese real-world setting. Their findings provide clinical insight into the management of periprocedural OAC therapy and OAC cessation during the remote period after CA.
Y.O. received research funding from Daiichi-Sankyo and Johnson&Johnson, accepted remuneration from Bayer Healthcare, Daiichi-Sankyo and Bristol-Meyers Squibb, and belongs to endowed departments of Boston Scientific Japan, Abbott Medical Japan, Japan Lifeline, Medtronic Japan, and Nihon Kohden.
