Published online: 2019-09-16 Review Article Risk of Gastrointestinal Bleed and Endoscopic Procedures on Antiplatelet and Antithrombotic Agents Partha Pal, Manu Tandan, Duvvuru Nageshwar Reddy Department of Medical The use of antiplatelet and antithrombotic agents has increased hand in hand with Gastroenterology, Asian the number and complexity of endoscopic procedures. Hence, the endoscopists Institute of Gastroenterology, Hyderabad, Telangana, India are often faced with considering endoscopy in patients on these agents. In this setting, to make informed decision, four key aspects are need to be considered. Abstract The type of antithrombotic or antiplatelet agent used and its characteristics, risk of thromboembolic events (which can lead to ischemic stroke or acute coronary syndrome, both of which carry high morbidity) due to withholding the drug, risk of bleeding (increases with invasiveness of procedure), and timing of procedure (elective or urgent) are the key factors to consider. We aim to discuss the risk of gastrointestinal bleed and endoscopic procedures on antiplatelet and antithrombotic agents focusing on Indian context based on recent Asia‑pacific guidelines along with other existing guidelines. Keywords: Antiplatelets, antithrombotic agents, endoscopy, gastrointestinal bleeding Introduction is taking. The knowledge of mechanism of action, astrointestinal (GI) bleed is one of the most onset and offset of action, pharmacokinetics, drug common medical emergencies in day‑to‑day interactions, and risk of bleeding with each agent is G essential for periendoscopic management of patients practice. With increase in age and comorbidities, on antiplatelet or antithrombotic agents. The timing of the use of antithrombotic agents (antiplatelet and discontinuation before endoscopy and resumption after anticoagulant agents) is widely prevalent, and this endoscopic hemostasis is discussed in detail later in the has added an additional dimension in the management manuscript. Summary of properties of oral antiplatelets of patients with GI bleed or those requiring a and anticoagulant agents is given in Table 2.[1,2] therapeutic endoscopic procedure. A balance between the risk of procedural hemorrhage and Host’s Risk of Thrombosis the risk of thromboembolism on discontinuation of Risk of thrombosis on stopping antithrombotic agents antithrombotic agents is essential. Knowledge of drug depends on underlying cardiovascular/cerebrovascular/ pharmacokinetics and urgency of the procedure are the peripheral vascular status or presence of prothrombotic other facts to consider [Table 1]. A close cooperation states. This determines the risk of thrombosis and is essential between physician, cardiologist, and the timing of resumption of antiplatelets or antithrombotic endoscopist for the proper management of such patients agents. who require GI endoscopy. Types of Antiplatelet or Antithrombotic Address for correspondence: Dr. Partha Pal, Department of Medical Gastroenterology, Asian Institute Drug of Gastroenterology, 6‑3‑661, Somajiguda, Hyderabad, Telangana, India. The endoscopist should inquire about the drugs E‑mail: [email protected] (antiplatelet and antithrombotic agents) that the patient This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows Access this article online others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical Quick Response Code: terms. Website: www.jdeonline.in For reprints contact: [email protected] How to cite this article: Pal P, Tandan M, Reddy DN. Risk of gastrointestinal DOI: 10.4103/jde.JDE_10_19 bleed and endoscopic procedures on antiplatelet and antithrombotic agents. J Dig Endosc 2019;10:XX‑XX. © 2019 Nigerian Journal of© Experimental 2019 Journal and of Digestive Clinical Biosciences Endoscopy | Published by Wolters Kluwer - Medknow 11 Pal, et al.: Endoscopy and antithrombotics Table 1: Key factors to consider for periprocedural MACEs was stable after 6 months in both DES and [4] management of patients on antiplatelets and BMS. anticoagulants undergoing endoscopy On the other hand, the British Society of Drug factors Host’s risk of Host’s risk Timing of Gastroenterology/European Society of GI Endoscopy thrombosis of bleeding procedure (BSG‑ESGE) and the American Society of Mechanism Cardiovascular status Ultrahigh‑risk Urgent of action (acute coronary procedure Gastroenterology (ASGE) guidelines are based on syndrome or stable the 2014 American College of Cardiology/American CAD) Heart Association guidelines that stated that the risk of Dose and Cerebrovascular status noncardiac surgery is high in patients with BMS placed efficacy within 1 month or DES placed within 12 months.[5] The Duration of Peripheral vascular High‑risk American College of Chest Physicians recommends action status procedure delaying noncardiac surgery for 6 weeks for BMS and Renal/hepatic Prothrombotic states Elective [6] clearance 6 months in case of DES. Drug Prosthetic valve Risk of thrombosis in prothrombotic states interactions Different societies have stratified patients according to Onset of Atrial fibrillation Low‑risk their risk of thromboembolism during discontinuation action procedure of warfarin. The criteria for bridging therapy differ in Risk of Structural cardiac bleeding valve disease different guidelines. In ESGE guidelines, nonvalvular History of venous atrial fibrillation (AF) was considered low risk thumbs‑embolism irrespective of their CHA2DS2VASc score (congestive CAD=Coronary artery disease heart failure – 1 point, hypertension – 1 point, age ≥75 years – 2 points, diabetes mellitus –1 point, Risk of thrombosis post coronary stent/coronary stroke – 2 points, vascular disease – 1 point, age artery disease/cerebrovascular or peripheral 65–74 years – 1 point, female sex – 1 point, and total arterial disease points – 9) as there is a significantly higher risk of The risk of stent thrombosis due to discontinuation bleeding with bridging therapy compared to no bridging of antithrombotic agents can be very high, high, and therapy in RE‑LY trial.[7] However, the data could not moderate/low based on timing of discontinuation be extrapolated to patients with mitral stenosis or after acute coronary syndrome/percutaneous coronary CHA2DS2VASc score >5 due to small number of such intervention (ACS/PCI): <6 weeks, 6 weeks–6 months, patients. The role of bridge therapy in AF with mitral and >6 months, respectively, according to APAGE/ [3] stenosis is also controversial, and the result of BRIDGE APSDE guidelines. Stable coronary artery disease, trial which showed foregoing bridging therapy is cerebrovascular disease, and peripheral arterial noninferior to periprocedural heparin bridging to disease also fall under low‑risk category. For very prevent arterial thromboembolism with lower risk high‑risk category, the procedure should be deferred, of bleeding.[8] In ESGE guidelines, AF with mitral and for high‑risk cases, defer procedure if possible stenosis is regarded as high risk of thromboembolism, to >6 months. For low‑risk cases, the procedure should but in APAGE/APSDE guidelines, it is regarded as low not be deferred. The difference between high and low risk with no need for bridging therapy. As patients of risk is that for discontinuing antithrombotic agents, nonvalvular AF with CHA2DS2VASc score >5 have high‑risk patients need heparin‑bridging therapy. These a high risk of thromboembolism, bridging therapy has have been detailed in Table 3. been recommended by APAGE/APSDE guidelines. In This recommendation is based on a recent retrospective contrast, the cutoff of the same score is >2 in ASGE [3,9,10] cohort study based on data of 42,000 patients guidelines. undergoing surgery within 24 months of placement of Although there are differences in the various guidelines, coronary stent. The incidence of major adverse cardiac the basic concept is either there is a high or low risk events (MACEs) after surgery within 6 weeks, 6 weeks of thromboembolism in the absence of anticoagulant, to 6 months, 6–12 months, and >12–24 months was and the high‑risk patients need bridging therapy by 11.6%, 6.4%, 4.2%, and 3.5%, respectively. MACE unfractionated heparin (UFH) (ASGE and APAGE/ incidence was not different between drug‑eluting APSDE) or low‑molecular‑weight heparin (LMWH) stent (DES) and bare metal stent (BMS), and risk of (BSG/ESGE). The most recent guidelines are by 12 Journal of Digestive Endoscopy ¦ Volume 10 ¦ Issue 1 ¦ January-March 2019 Pal, et al.: Endoscopy and antithrombotics Table 2: Summary of properties of commonly used oral antiplatelets and anticoagulant agents Mechanism of Dose Efficacy Onset of Duration of Renal/hepatic Drug Risk of action action action clearance interaction bleeding Aspirin Irreversible 75‑300 mg/day, 25% reduction 5‑30 min Antiplatelet Liver 90%, renal Acetazolamide 1%‑3% per inhibition 160 mg/day in the risk of effect 10% and alcohol year of platelet for complete cardiovascular persists for increases the cyclooxygenase inhibition of death, MI, or 7‑10 days toxic effects (COX)‑1 platelet COX‑1 stroke of salicylates Clopidogrel Inhibit Clopidogrel‑75 Compared Onset of Antiplatelet Renal and CYP2C19 Combining and ADP‑ induced mg/day, loading with aspirin, action effect hepatic inhibitor. clopidogrel Prasugrel platelet dose ‑ 300 mg; clopidogrel 4‑6 h, persists up to clearance 50% Concomitant