Continuation or discontinuation of antithrombotics in clinical daily practice of gastrointestinal endoscopy: Has a paradigm shift occurred in Japan?

Field: Medicine (Health Sciences)

As the number of patients receiving antithrombotics has been rapidly increasing, management of antithrombotics during the periendoscopic period has become a matter of vital concern for endoscopists. Antithrombotics act like a double-edged sword in clinical daily practice because they can decrease thromboembolism risk and increase bleeding risk at the same time. These two aspects of antithrombotics cause great dilemma, especially during the periendoscopic period, because endoscopy is sometimes associated with severe bleeding events even in patients not receiving antithrombotics. However, careless cessation of antithrombotics can cause severe thromboembolism; therefore, endoscopists must make a difficult decision before endoscopy as to whether or not to continue them. The previous Japan Gastroenterological Endoscopy Society (JGES) guidelines placed more emphasis on the prevention of bleeding rather than on thromboembolism, although the following validations of the guidelines revealed lethal events during the cessation period. Before 2005, common management of antithrombotics was setting a cessation period long enough to completely flush out their medical effects before endoscopy. However, there was no solid evidence to support this. Additionally, a not negligible number of severe thromboembolic events had occurred during the long cessation period before endoscopy.1 For these reasons, the JGES guidelines were revised in 2005. These revised guidelines were revolutionary in that shorter cessation periods of aspirin and ticlopidine were recommended, although the adherence rate was low for various reasons.2 At approximately the same time, Western guidelines had already permitted endoscopic procedures including those with a high risk of bleeding without discontinuation of aspirin. Discrepancy between these guidelines was because of potential racial differences concerning the risks of thromboembolism and bleeding, although there was not enough evidence to support this. Consequently, considering the significant number of lethal thromboembolic complications during the discontinuation period, the JGES guidelines were revised again in 2012, based upon existing guidelines in Western countries. These guidelines are characterized by a partial permission of endoscopic procedures without discontinuation of antithrombotics. It means a significant redirection of clinical daily practice of gastrointestinal endoscopy in Japan. In this issue of Digestive Endoscopy, Fujita et al. reports changes of clinical daily practice concerning the management of antithrombotics during the periendoscopic period after revision of the JGES guidelines.3 Their retrospective study demonstrates that endoscopic biopsy, the most common endoscopic procedure, is feasible without discontinuation of antithrombotics as long as the international normalized ratio (INR) is ascertained to be within the therapeutic range for patients taking anticoagulants. In their manuscript, approximately one-eighth of patients underwent endoscopy without discontinuation, and one-fifth of them underwent biopsy. Because their study period was immediately 1 year after revision of the JGES guidelines, their results demonstrating the safety of biopsy without discontinuation of antithrombotics will promote the further spread of it. However, as a limitation of their study design, the authors could not sufficiently evaluate the rate of subclinical asymptomatic bleeding after endoscopic biopsy. Therefore, considering its retrospective design and small number of participants, that study does not necessarily provide an assurance of the safety of endoscopic biopsies without discontinuation of all types of antithrombotics in patients with various comorbidities. Moreover, their study revealed that not a small number of patients were taking multiple antithrombotic agents. Evaluation of subclinical asymptomatic bleeding in such patients will be mandatory in the future because they are reported to be at a higher risk of gastrointestinal bleeding compared to those taking single antithrombotics. The present guidelines contain two principles. The first principle is to discontinue antithrombotics with low priority before endoscopy to reduce unnecessary risk of bleeding. The second principle is to postpone endoscopic procedures as far as possible until antithrombotics can be discontinued safely. After that, we must carry out endoscopic procedures carefully, making an effort to minimize invasiveness. In that regard, we necessarily have to stand by the principle that endoscopists must manage each patient taking antithrombotics considering the pros and cons carefully. The present JGES guidelines still have some problems to be resolved. The present JGES guidelines permit high-bleeding-risk procedures without discontinuation of a few types of antithrombotics. However, this is also based upon guidelines used in Western countries, although there is not enough evidence to support this. It is also controversial as to whether one should give a heparin bridge for patients taking anticoagulants, as recommended in the present JGES guidelines. Additionally, the article by Fujita et al. shows that an increasing number of patients are taking new oral anticoagulants (NOAC). One of the major problems of the previous JGES guidelines was lack of a description of emerging antithrombotics. It did not show the recommended management of clopidogrel as today's most widely accepted thienopyridine derivative. The manuscript of Fujita et al. shows that 4.8% patients were receiving dabigatran, whereas no patient was receiving it in our previous investigation in 2009.4 NOAC such as rivaroxaban and apixaban have become available in clinical daily practice but are not mentioned in the present JGES guidelines. Therefore, there is an urgent need to accumulate evidence concerning the management of these NOAC during the periendoscopic period. Undoubtedly, the final goal of the guidelines for the management of antithrombotics is to carry out all endoscopic procedures safely for all patients taking antithrombotics. As mentioned above, the present JGES guidelines require further validation. In contrast, the present JGES guidelines provide for circumstances where various clinical trials can be carried out by providing a higher degree of freedom in clinical daily practice compared to the previous JGES guidelines. In particular, endoscopic submucosal dissection (ESD), which was developed in Japan, has few reports to validate its safety without discontinuation of antithrombotics. Recently, Sanomura et al. reported the feasibility of gastric ESD without discontinuation of aspirin for patients taking antiplatelet agents from a single institute.5 Under these guidelines, further accumulation of evidence concerning this problem is expected. Also, further accumulation of evidence is the duty of endoscopists in Japan, because Japan is where endoscopy has originated and developed. Authors declare no conflict of interests concerning this article.