The American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) released clinical guidelines for the periendoscopic management of antithrombotic drugs during acute gastrointestinal (GI) bleeding and in the elective endoscopic setting. The recommendations were published in the American Journal of Gastroenterology.
In 2021, ACG and CAG convened in a working group to create guidelines in response to a series of predefined clinical questions about antithrombotic drugs in the endoscopic setting. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used: A systematic review of the literature was performed, following which proposed guidelines were voted on by participating experts in gastroenterology, cardiology, and thrombosis. Guidelines were put forth for both the emergent and elective settings.
Management of antithrombotic agents in the setting of acute GI bleed
Acute GI bleeding was defined as patients hospitalized or under observation with “acute…bleeding manifesting as melena, hematochezia, or hematemesis.” Recommendations were developed for the reversal and/or management of antithrombotic agents of interest.
- Reversal of vitamin K antagonists (i.e., warfarin) – In patients on warfarin who are hospitalized or under observation with acute GI bleeding, investigators recommended against the use of fresh frozen plasma. While fresh frozen plasma is a plausible means of VKA effect reversal, evidence suggesting this option reduces the risk of GI bleeding is sparse and of low quality. Regarding prothrombin complex concentrate (PCC) administration for VKA effect reversal, evidence was lacking to support or oppose its use. However, in patients with a life-threatening bleed, patients with a supratherapeutic international normalized ratio (INR), or patients for whom massive blood transfusion is contraindicated, PCC administration is recommended over fresh frozen plasma. Finally, investigators suggested against the administration of vitamin K to patients on warfarin, as no clinical evidence was available to suggest that vitamin K reduces or prevents further GI bleeding.
- Reversal of thrombin inhibitors – For patients on dabigatran who are hospitalized or under observation with acute GI bleeding, investigators recommended against the administration of idarucizumab. Study data were limited regarding the benefits of idarucizumab for dabigatran reversal. However, idarucizumab may be an option for patients with severe GI bleeding who have taken dabigatran in the past 24 hours.
- Reversal of rivaroxaban or apixaban with andexanet alfa – Investigators recommended against andexanet alfa administration for patients taking rivaroxaban or apixaban. Just 1 published study examined the effects of andexanet alfa administration on the reversal of these agents. The study had serious methodological limitations and lacked a control group. Further, andexanet alfa is an expensive medication, with a high-dose regimen costing up to $49,500. As such, the panel recommended against its regular use in patients with GI bleeds, though in severe cases it may be considered.
- Reversal of direct oral anticoagulants (DOACs) with PCC – Investigators recommended against the administration of PCC to reverse DOACs. The literature search identified only 2 cohort studies assessing PCC use in patients taking DOACs. Both studies had substantial methodological limitations, and PCC efficacy was unclear. Given the uncertainty of available evidence, authors recommend against routine use of PCC to reverse DOACs. However, in patients with a life-threatening GI bleed, PCC may be considered.
- Reversal of antiplatelets with platelet transfusion – Investigators recommended against platelet transfusions for patients taking antiplatelet agents. In published studies, platelet transfusions were associated with an increased risk for mortality, further bleeding, and thrombotic events.
- Holding vs continuing acetylsalicylic acid (ASA) – For patients on cardiac ASA for secondary cardiovascular prevention, investigators recommended against cessation of ASA during a GI bleed. In patients whose ASA was interrupted, investigators suggested that ASA be resumed on the day hemostasis is endoscopically confirmed.
Management of antithrombotic agents in the setting of elective endoscopy
Recommendations in the elective endoscopy setting focused on the cessation and/or resumption of antithrombotic agents in patients undergoing scheduled, elective endoscopic procedures. These recommendations excluded patients at high risk for thromboembolic events.
- Anticoagulants – Investigators recommended that patients on warfarin continue taking the drug as opposed to a 1- to 7-day interruption in the periprocedural period. Among patients whose warfarin was interrupted, no consensus could be reached regarding the resumption of warfarin on the same day vs 1 to 7 days after procedure. Similarly, in patients whose DOAC regimen was interrupted, no consensus was reached regarding resumption timeline. As with warfarin, DOAC resumption on the same day vs within 1 to 7 days had comparable outcomes.
- Antiplatelets – For patients on dual antiplatelet therapy for secondary prevention, investigators recommended the temporary interruption of the P2Y12 receptor inhibitor and continuation of ASA. For patients on single antiplatelet therapy, however, authors could not reach a recommendation for or against the interruption of the P2Y12 inhibitor. For patients on ASA monotherapy, authors suggested against its interruption prior to the procedure. Regarding the resumption of P2Y12 inhibitor therapy, no consensus could be reached regarding the benefits of same-day resumption vs resumption within 1 to 7 days of procedure.
While thorough, these recommendations were often conditional and based on low certainty evidence. Consensus could not be reached on certain clinical questions due to absence of high-quality data. Future studies are necessary to better inform antithrombotic agent management in the case of GI bleeds or elective endoscopy.
Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Abraham NS, Barkun AN, Sauer BG, et al. American College of Gastroenterology-Canadian Association of Gastroenterology clinical practice guideline: management of anticoagulants and antiplatelets during acute gastrointestinal bleeding and the periendoscopic period. Am J Gastroenterol. Published online March 17, 2022. doi: 10.14309/ajg.0000000000001627