Management of antithrombotic medications in elective endoscopy

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Antithrombotic therapy is increasingly used to either reduce the risk of or treat thromboembolic episodes in patients with various medical conditions such as ischemic and valvular heart disease, atrial fibrillation (AF), cerebrovascular disease, peripheral arterial disease, venous thromboembolism (VTE) and hypercoagulable diseases. Antithrombotics include medications classified as anticoagulants or antiplatelets. Anticoagulants work by interfering with the native clotting cascade and consist of four main classes: vitamin K antagonists (VKA), heparin derivatives, direct factor Xa inhibitors, and direct thrombin inhibitors. Direct oral anticoagulants (DOACs) refer to dabigatran (a direct thrombin inhibitor) and the factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban).

Antiplatelets, on the other hand, work by decreasing platelet aggregation and thus preventing thrombus formation; they include P2Y12 receptor inhibitors, protease-activated receptor-1 inhibitors, glycoprotein IIb/IIIa receptor inhibitors, acetylsalicylic acid (ASA), and nonsteroidal anti-inflammatory drugs. All of these agents may directly cause or increase the risk of gastrointestinal (GI) bleeding from luminal sources such as ulcers or diverticula, as well as after endoscopic interventions such as polypectomy. However, there is also a risk of thromboembolic consequences if some of these agents are withheld. Thus, the management of patients receiving antithrombotic agents and undergoing GI endoscopy represents an important clinical challenge and something that every GI physician has to deal with routinely.

Dr. Wenfei Wang

The goal of this review is to discuss the optimal strategy for managing antithrombotics in patients undergoing elective endoscopy based on current available evidence and published clinical guidelines.1-4 Much of our discussion will review recommendations from the recently published joint American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guidelines on management of anticoagulants and antiplatelets in the periendoscopic period by Abraham et al.4

Factors that guide decision-making

The two most vital factors to consider prior to performing endoscopic procedures in patients receiving antithrombotic therapy are to assess the risk of bleeding associated with the procedure and to assess the risk of thromboembolism associated with the underlying medical condition for which the antithrombotic agents are being used. In addition, it is also important to keep in mind the individual characteristics of the antithrombotic agent(s) used when making these decisions.

Estimating procedure-related bleeding risk

Various endoscopic procedures have different risks of associated bleeding. Although guidelines from GI societies may differ when classifying procedures into low or high risk, it is important to know that most of the original data on postprocedural bleeding risks are from studies conducted in patients who are not on complex antithrombotic regimens and thus may not accurately reflect the bleeding risk of patients using newer antithrombotic therapies.1,4-7

Dr. Neil Sengupta

Traditionally, some of the common low-risk procedures have included diagnostic EGD and colonoscopy with or without biopsy, ERCP without sphincterotomy, biliary stent placement, and push or balloon-assisted enteroscopy. On the other hand, endoscopic procedures associated with interventions are known to have higher bleeding risk, and other procedural factors can influence this risk as well.8 For example, polypectomy, one of the most common interventions during endoscopy, is associated with bleeding risk ranging from 0.3% to 10% depending on multiple factors including polyp size, location, morphology (nonpolypoid, sessile, pedunculated), resection technique (cold or hot forceps, cold or hot snare), and type of cautery used.9 For some procedures, such as routine screening colonoscopy, however, the preprocedure estimate of bleeding risk can be uncertain because it is unclear if a high risk intervention (e.g., polypectomy of large polyp) will be necessary. For example, in the most recent ACG/CAG guidelines, colonoscopy with polypectomy < 1cm is considered a low/moderate risk bleeding procedure, whereas polypectomy > 1cm is considered high risk for bleeding.4 In these situations, the management of antithrombotic medications may depend on the individual patient’s risk of thrombosis and the specific antithrombotic agent. In the example of a patient undergoing colonoscopy while on antithrombotic medications, the bleeding risk associated with polypectomy can potentially be reduced by procedural techniques such as preferential use of cold snare polypectomy. Further high-quality data on the optimal procedural technique to reduce postpolypectomy bleeding in patients on antithrombotic medications is needed to help guide management.
 

 

 

Estimating thromboembolic risk

The risk of thromboembolic events in patients who are withholding their antithrombotic therapy for an endoscopic procedure depends on their underlying condition and individual characteristics. In patients who are on antithrombotic therapy for stroke prevention in non-valvular AF, the risk of cerebral thromboembolism in these patients is predictable using the CHA2DS2Vasc index.10 This scoring index includes heart failure, hypertension, age 75 years or older, diabetes mellitus, prior stroke or transient ischemic attack (TIA), vascular disease, age 65-74 years, and sex categories.

Patients with previous VTE on anticoagulation or those who have mechanical heart valves may have different risk factors for thromboembolic episodes. Among patients with VTE, time from initial VTE, history of recurrent VTE with antithrombotic interruption, and presence of underlying thrombophilia are most predictive of future thromboembolic risk. And for patients with mechanical heart valves, presence of a mitral valve prosthesis, and the presence or absence of associated heart failure and AF determine the annual risk of thromboembolic events. Bioprosthetic valves are generally considered low risk.

In patients with coronary artery disease (CAD), high thrombosis risk scenarios with holding antiplatelets include patients within 3 months of an acute coronary syndrome (ACS) event, within 6 months of a drug-eluting stent (DES) placement, or within 1 month of a bare metal coronary stent (BMS) placement. In addition, patients with ACS that occurred within the past 12 months of DES placement or within 2 months of BMS placement are also considered high risk.11,12 Even beyond these periods, certain patients may still be at high risk of stent occlusion. In particular, patients with a prior history of stent occlusion, ACS or ST elevation myocardial infection, prior multivessel percutaneous coronary intervention, diabetes, renal failure, or diffuse CAD are at higher risk of stent occlusion or ACS events with alteration of antithrombotic therapy.13 Thus, modification of antithrombotic regimens in these patients should be cautiously approached.
 

Management of antithrombotics prior to elective endoscopy

In patients who need elective endoscopic procedures, if the indication for antithrombotic therapy is short-term, the procedure is probably best delayed until after that period.13 For patients on long-term or lifelong antithrombotic treatment, the decision to temporarily hold the treatment for endoscopy should occur after a discussion with the patient and all of the involved providers. In some high-risk patients, these agents cannot be interrupted; therefore, clinicians must carefully weigh the risks and benefits of the procedure before proceeding with endoscopy. For patients who are known to be undergoing an elective endoscopic procedure, antithrombotic medications may or may not need to be held prior to the procedure depending on the type of therapy. For example, according to the recent ACG/CAG guidelines, warfarin should be continued, whereas DOACs should be temporarily stopped for patients who are undergoing elective/planned endoscopic GI procedures.

Unfractionated heparin (UFH) administered as a continuous intravenous infusion can generally be held 3-4 hours before the procedure, given its short half-life. Low molecular weight heparin (LMWH), including enoxaparin and dalteparin, should be stopped 24 hours prior to the procedure.2,14 Fondaparinux is a synthetic X-a inhibitor that requires discontinuation at least 36 hours preceding a high risk procedure. For patients on warfarin who are undergoing elective endoscopic procedures that are low risk for inducing bleeding, warfarin can be continued, as opposed to temporarily interrupted, although the dose should be omitted the morning of the procedure.4 For those who are undergoing high-risk endoscopic procedures (including colonoscopy with possible polypectomy > 1 cm), 5 days of temporary interruption without periprocedural bridging is appropriate in most patients. This is contrary to previous guidelines, which had recommended bridging for patients with a CHA2DS2Vasc score ≥ 2. Recent impactful randomized trials (BRIDGE and PERIOP-2) have called into question the benefit of periprocedural bridging with LMWH. Avoiding bridging anticoagulation was generally found to be similar to bridging in regard to prevention of thromboembolic complications, but importantly was associated with a decreased risk of major bleeding.15,16 Of note, periprocedural bridging may still be appropriate in a small subset of patients, including those with mechanical valves, AF with CHADS2 score > 5, and previous thromboembolism during temporary interruption of VKAs. The decision to bridge or not should ideally be made in a multidisciplinary fashion.15-20

Data are lacking on the ideal strategy for periendoscopic DOAC management. As mentioned above, for patients on DOACs who are undergoing elective endoscopic GI procedures, temporarily interrupting DOACs rather than continuing them is recommended. Currently, there are no randomized controlled trials addressing the management of DOACs in the periendoscopic period. However, based on five cohort studies, the ideal duration of DOAC interruption before endoscopic procedures may be between 1 and 2 days, excluding the day of the procedure.21-25 This strategy allows for a short preprocedural duration of DOAC interruption and likely provides a balance between bleeding and thromboembolism risk. Importantly, there are no reliable laboratory assays to assess the anticoagulant effect of DOACs, and an individual patient’s degree of renal dysfunction may impact how long the DOAC should be held. In general, the anti-Xa drugs should be held for 1-2 days if the creatinine clearance (CrCl) is ≥ 60 mL/min, for 3 days if the CrCl is between 30 mL/min and 59 mL/min, and for 4 days if the CrCl is less than 30 mL/min.26 For edoxaban, the recommendation is to hold at least 24 hours before high-risk procedures. The recommendation for stopping dabigatran is 2-3 days before a high-risk procedure in patients with CrCl more than 80 mL/min, 3-4 days prior if between 30 and 49 mL/min, and 4-6 days prior if less than 30 mL/min respectively.27

In regard to antiplatelet management, ASA and the P2Y12 receptor inhibitors (e.g. clopidogrel, prasugrel, and ticagrelor) are the most commonly utilized antiplatelets in patients undergoing endoscopic procedures. For patients who are on ASA monotherapy, whether 81 mg or 325 mg daily, for secondary cardiovascular prevention, no interruption of ASA therapy is necessary for elective procedures. The benefit of ASA for secondary cardiovascular prevention and the possible reduction in thrombotic events seen in RCTs of nonendoscopic surgical procedures is well known. However, there may be certain exceptions in which aspirin should be temporarily held. For example, short-term interruption of ASA could be considered in high risk procedures such as biliary or pancreatic sphincterotomy, ampullectomy, and peroral endoscopic myotomy. For patients on single antiplatelet therapy with a P2Y12 receptor inhibitor who are undergoing elective endoscopic GI procedures, the recent CAG/ACG guidelines did not provide a clear recommendation for or against temporary interruption of the P2Y12 receptor inhibitor. Although interruption of a P2Y12 receptor inhibitor should theoretically decrease a patient’s risk of bleeding, the available evidence reported a nonsignificant increased bleeding risk in patients who stop a P2Y12 receptor inhibitor for an elective endoscopic procedure compared with those who continue the medication.28,29 Therefore, until further data are available, for patients on P2Y12 receptor monotherapy, a reasonable strategy would be to temporarily hold therapy prior to high risk endoscopic procedures, assuming the patients are not at high cardiovascular risk. Clopidogrel and prasugrel have to be stopped 5-7 days prior to allow normal platelet aggregation to resume as opposed to ticagrelor, a reversible P2Y12 receptor inhibitor that can be stopped 3-5 days prior.30

Lastly, for patients who are on dual antiplatelet therapy (DAPT) for secondary prevention, continuation of ASA and temporary interruption of the P2Y12 receptor inhibitor is recommended while undergoing elective endoscopy. Studies have shown that those who discontinued both had a much higher incidence of stent thrombosis compared with those who remained on aspirin alone.4,28,31

 

 

Resumption of antithrombotic therapy after endoscopy

In general, antithrombotic therapy should be resumed upon completion of the procedure unless there remains a persistent risk of major bleeding.1,14 This consensus is based on studies available on warfarin and heparin products, with minimal literature available regarding the resumption of DOACs. The benefits of immediate re-initiation of antithrombotic therapy for the prevention of thromboembolic events should be weighed against the risk of hemorrhage associated with the specific agent, the time to onset of the medication, and procedure-specific circumstances. For the small subset of patients on warfarin with a high risk of thromboembolism (e.g., mechanical heart valve), bridging with LMWH should be started at the earliest possible time when there is no risk of major bleeding and continued until the international normalized ratio (INR) reaches a therapeutic level with warfarin. For patients at a lower risk of thromboembolism, warfarin should be restarted within 24 hours of the procedure. In addition, because of the shorter duration of DOACs, if treatment with these agents cannot resume within 24 hours of a high-risk procedure, bridge therapy should be considered with UFH or LMWH in patients with a high risk of thrombosis.18 In patients receiving DOACs for stroke prophylaxis in AF, the DOACS can be safely resumed 1 day after low-risk procedures and 2-3 days after high-risk procedures without the need for bridging.25 All antiplatelet agents should be resumed as soon as hemostasis is achieved.

Conclusion

Antithrombotic therapy is increasingly used given the aging population, widespread burden of cardiovascular comorbidities, and expanding indications for classes of medications such as direct oral anticoagulants. Given the association with antithrombotic medications and gastrointestinal bleeding, it is essential for gastroenterologists to understand the importance, necessity, and timing when holding these medications for endoscopic procedures. Even with the practice guidelines available today to help clinicians navigate certain situations, each patient’s antithrombotic management may be different, and communication with the prescribing physicians and including patients in the decision-making process is essential before planned procedures.

Dr. Wang is a gastroenterology fellow at the University of Chicago. Dr. Sengupta is an associate professor at the University of Chicago. They reported no funding or conflicts of interest.

 

 

References

1. ASGE Standards of Practice Committee, Acosta RD et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83(1):3-16.

2. Veitch AM et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Endoscopy. 2016;48(4):c1. doi: 10.1055/s-0042-122686.

3. Chan FKL et al. Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: Joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines. Gut. 2018;67(3):405-17.

4. Abraham NS 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. 2022;117(4):542-58.

5. Boustière C et al. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2011;43(5):445-61.

6. Fujimoto K et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc. 2014;26(1):1-14.

7. Wilke T et al. Patient preferences for oral anticoagulation therapy in atrial fibrillation: A systematic literature review. Patient 2017;10(1):17-37.

8. Gerson LB et al. Adverse events associated with anticoagulation therapy in the periendoscopic period. Gastrointest Endosc. 2010 Jun;71(7):1211-17.e2.

9. Horiuchi A et al. Removal of small colorectal polyps in anticoagulated patients: A prospective randomized comparison of cold snare and conventional polypectomy. Gastrointest Endosc 2014;79(3):417-23.

10. Lip GYH et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest. 2010;137(2):263-72.

11. 2012 Writing Committee Members, Jneid H et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (Updating the 2007 guideline and replacing the 2011 focused update): A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2012;126(7):875-910.

12. Douketis JD et al. Perioperative management of antithrombotic therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e326S-e350S.

13. Becker RC et al. Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures. J Am Coll Cardiol. 2009;54(24):2261-76.

14. Kwok A and Faigel DO. Management of anticoagulation before and after gastrointestinal endoscopy. Am J Gastroenterol. 2009;104(12):3085-97; quiz 3098.

15. Douketis JD et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373(9):823-33.

16. Kovacs MJ et al. Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): Double blind randomised controlled trial. BMJ 2021;373:n1205.

17. Tafur A and Douketis J. Perioperative management of anticoagulant and antiplatelet therapy. Heart 2018;104(17):1461-7.

18. Kato M et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment: 2017 appendix on anticoagulants including direct oral anticoagulants. Dig Endosc. 2018;30(4):433-40.

19. Inoue T et al. Clinical features of postpolypectomy bleeding associated with heparin bridge therapy. Dig Endosc. 2014;26(2):243-9.

20. Takeuchi Y et al. Continuous anticoagulation and cold snare polypectomy versus heparin bridging and hot snare polypectomy in patients on anticoagulants with subcentimeter polyps: A randomized controlled trial. Ann Intern Med. 2019;171(4):229-37.

21. Ara N et al. Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan. Dig Endosc. 2015;27(4):458-64.

22. Yanagisawa N et al. Postpolypectomy bleeding and thromboembolism risks associated with warfarin vs. direct oral anticoagulants. World J Gastroenterol. 2018;24(14):1540-9.

23. Arimoto J et al. Safety of cold snare polypectomy in patients receiving treatment with antithrombotic agents. Dig Dis Sci. 2019;64(11):3247-55.

24. Heublein V et al. Gastrointestinal endoscopy in patients receiving novel direct oral anticoagulants: Results from the prospective Dresden NOAC registry. J Gastroenterol. 2018;53(2):236-46.

25. Douketis JD et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med. 2019;179(11):1469-78.

26. Dubois V et al. Perioperative management of patients on direct oral anticoagulants. Thromb J. 2017;15:14.

27. Weitz JI et al. Periprocedural management and approach to bleeding in patients taking dabigatran. Circulation. 2012 Nov 13;126(20):2428-32.

28. Chan FKL et al. Risk of postpolypectomy bleeding with uninterrupted clopidogrel therapy in an industry-independent, double-blind, randomized trial. Gastroenterology. 2019;156(4):918-25.

29. Watanabe K et al. Effect of antiplatelet agent number, types, and pre-endoscopic management on postpolypectomy bleeding: Validation of endoscopy guidelines. Surg Endosc. 2021;35(1):317-25.

30. Gurbel PA et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: The ONSET/OFFSET study. Circulation. 2009;120(25):2577-85.

31. Eisenberg MJ et al. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation. 2009;119(12):1634-42.
 

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Antithrombotic therapy is increasingly used to either reduce the risk of or treat thromboembolic episodes in patients with various medical conditions such as ischemic and valvular heart disease, atrial fibrillation (AF), cerebrovascular disease, peripheral arterial disease, venous thromboembolism (VTE) and hypercoagulable diseases. Antithrombotics include medications classified as anticoagulants or antiplatelets. Anticoagulants work by interfering with the native clotting cascade and consist of four main classes: vitamin K antagonists (VKA), heparin derivatives, direct factor Xa inhibitors, and direct thrombin inhibitors. Direct oral anticoagulants (DOACs) refer to dabigatran (a direct thrombin inhibitor) and the factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban).

Antiplatelets, on the other hand, work by decreasing platelet aggregation and thus preventing thrombus formation; they include P2Y12 receptor inhibitors, protease-activated receptor-1 inhibitors, glycoprotein IIb/IIIa receptor inhibitors, acetylsalicylic acid (ASA), and nonsteroidal anti-inflammatory drugs. All of these agents may directly cause or increase the risk of gastrointestinal (GI) bleeding from luminal sources such as ulcers or diverticula, as well as after endoscopic interventions such as polypectomy. However, there is also a risk of thromboembolic consequences if some of these agents are withheld. Thus, the management of patients receiving antithrombotic agents and undergoing GI endoscopy represents an important clinical challenge and something that every GI physician has to deal with routinely.

Dr. Wenfei Wang

The goal of this review is to discuss the optimal strategy for managing antithrombotics in patients undergoing elective endoscopy based on current available evidence and published clinical guidelines.1-4 Much of our discussion will review recommendations from the recently published joint American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guidelines on management of anticoagulants and antiplatelets in the periendoscopic period by Abraham et al.4

Factors that guide decision-making

The two most vital factors to consider prior to performing endoscopic procedures in patients receiving antithrombotic therapy are to assess the risk of bleeding associated with the procedure and to assess the risk of thromboembolism associated with the underlying medical condition for which the antithrombotic agents are being used. In addition, it is also important to keep in mind the individual characteristics of the antithrombotic agent(s) used when making these decisions.

Estimating procedure-related bleeding risk

Various endoscopic procedures have different risks of associated bleeding. Although guidelines from GI societies may differ when classifying procedures into low or high risk, it is important to know that most of the original data on postprocedural bleeding risks are from studies conducted in patients who are not on complex antithrombotic regimens and thus may not accurately reflect the bleeding risk of patients using newer antithrombotic therapies.1,4-7

Dr. Neil Sengupta

Traditionally, some of the common low-risk procedures have included diagnostic EGD and colonoscopy with or without biopsy, ERCP without sphincterotomy, biliary stent placement, and push or balloon-assisted enteroscopy. On the other hand, endoscopic procedures associated with interventions are known to have higher bleeding risk, and other procedural factors can influence this risk as well.8 For example, polypectomy, one of the most common interventions during endoscopy, is associated with bleeding risk ranging from 0.3% to 10% depending on multiple factors including polyp size, location, morphology (nonpolypoid, sessile, pedunculated), resection technique (cold or hot forceps, cold or hot snare), and type of cautery used.9 For some procedures, such as routine screening colonoscopy, however, the preprocedure estimate of bleeding risk can be uncertain because it is unclear if a high risk intervention (e.g., polypectomy of large polyp) will be necessary. For example, in the most recent ACG/CAG guidelines, colonoscopy with polypectomy < 1cm is considered a low/moderate risk bleeding procedure, whereas polypectomy > 1cm is considered high risk for bleeding.4 In these situations, the management of antithrombotic medications may depend on the individual patient’s risk of thrombosis and the specific antithrombotic agent. In the example of a patient undergoing colonoscopy while on antithrombotic medications, the bleeding risk associated with polypectomy can potentially be reduced by procedural techniques such as preferential use of cold snare polypectomy. Further high-quality data on the optimal procedural technique to reduce postpolypectomy bleeding in patients on antithrombotic medications is needed to help guide management.
 

 

 

Estimating thromboembolic risk

The risk of thromboembolic events in patients who are withholding their antithrombotic therapy for an endoscopic procedure depends on their underlying condition and individual characteristics. In patients who are on antithrombotic therapy for stroke prevention in non-valvular AF, the risk of cerebral thromboembolism in these patients is predictable using the CHA2DS2Vasc index.10 This scoring index includes heart failure, hypertension, age 75 years or older, diabetes mellitus, prior stroke or transient ischemic attack (TIA), vascular disease, age 65-74 years, and sex categories.

Patients with previous VTE on anticoagulation or those who have mechanical heart valves may have different risk factors for thromboembolic episodes. Among patients with VTE, time from initial VTE, history of recurrent VTE with antithrombotic interruption, and presence of underlying thrombophilia are most predictive of future thromboembolic risk. And for patients with mechanical heart valves, presence of a mitral valve prosthesis, and the presence or absence of associated heart failure and AF determine the annual risk of thromboembolic events. Bioprosthetic valves are generally considered low risk.

In patients with coronary artery disease (CAD), high thrombosis risk scenarios with holding antiplatelets include patients within 3 months of an acute coronary syndrome (ACS) event, within 6 months of a drug-eluting stent (DES) placement, or within 1 month of a bare metal coronary stent (BMS) placement. In addition, patients with ACS that occurred within the past 12 months of DES placement or within 2 months of BMS placement are also considered high risk.11,12 Even beyond these periods, certain patients may still be at high risk of stent occlusion. In particular, patients with a prior history of stent occlusion, ACS or ST elevation myocardial infection, prior multivessel percutaneous coronary intervention, diabetes, renal failure, or diffuse CAD are at higher risk of stent occlusion or ACS events with alteration of antithrombotic therapy.13 Thus, modification of antithrombotic regimens in these patients should be cautiously approached.
 

Management of antithrombotics prior to elective endoscopy

In patients who need elective endoscopic procedures, if the indication for antithrombotic therapy is short-term, the procedure is probably best delayed until after that period.13 For patients on long-term or lifelong antithrombotic treatment, the decision to temporarily hold the treatment for endoscopy should occur after a discussion with the patient and all of the involved providers. In some high-risk patients, these agents cannot be interrupted; therefore, clinicians must carefully weigh the risks and benefits of the procedure before proceeding with endoscopy. For patients who are known to be undergoing an elective endoscopic procedure, antithrombotic medications may or may not need to be held prior to the procedure depending on the type of therapy. For example, according to the recent ACG/CAG guidelines, warfarin should be continued, whereas DOACs should be temporarily stopped for patients who are undergoing elective/planned endoscopic GI procedures.

Unfractionated heparin (UFH) administered as a continuous intravenous infusion can generally be held 3-4 hours before the procedure, given its short half-life. Low molecular weight heparin (LMWH), including enoxaparin and dalteparin, should be stopped 24 hours prior to the procedure.2,14 Fondaparinux is a synthetic X-a inhibitor that requires discontinuation at least 36 hours preceding a high risk procedure. For patients on warfarin who are undergoing elective endoscopic procedures that are low risk for inducing bleeding, warfarin can be continued, as opposed to temporarily interrupted, although the dose should be omitted the morning of the procedure.4 For those who are undergoing high-risk endoscopic procedures (including colonoscopy with possible polypectomy > 1 cm), 5 days of temporary interruption without periprocedural bridging is appropriate in most patients. This is contrary to previous guidelines, which had recommended bridging for patients with a CHA2DS2Vasc score ≥ 2. Recent impactful randomized trials (BRIDGE and PERIOP-2) have called into question the benefit of periprocedural bridging with LMWH. Avoiding bridging anticoagulation was generally found to be similar to bridging in regard to prevention of thromboembolic complications, but importantly was associated with a decreased risk of major bleeding.15,16 Of note, periprocedural bridging may still be appropriate in a small subset of patients, including those with mechanical valves, AF with CHADS2 score > 5, and previous thromboembolism during temporary interruption of VKAs. The decision to bridge or not should ideally be made in a multidisciplinary fashion.15-20

Data are lacking on the ideal strategy for periendoscopic DOAC management. As mentioned above, for patients on DOACs who are undergoing elective endoscopic GI procedures, temporarily interrupting DOACs rather than continuing them is recommended. Currently, there are no randomized controlled trials addressing the management of DOACs in the periendoscopic period. However, based on five cohort studies, the ideal duration of DOAC interruption before endoscopic procedures may be between 1 and 2 days, excluding the day of the procedure.21-25 This strategy allows for a short preprocedural duration of DOAC interruption and likely provides a balance between bleeding and thromboembolism risk. Importantly, there are no reliable laboratory assays to assess the anticoagulant effect of DOACs, and an individual patient’s degree of renal dysfunction may impact how long the DOAC should be held. In general, the anti-Xa drugs should be held for 1-2 days if the creatinine clearance (CrCl) is ≥ 60 mL/min, for 3 days if the CrCl is between 30 mL/min and 59 mL/min, and for 4 days if the CrCl is less than 30 mL/min.26 For edoxaban, the recommendation is to hold at least 24 hours before high-risk procedures. The recommendation for stopping dabigatran is 2-3 days before a high-risk procedure in patients with CrCl more than 80 mL/min, 3-4 days prior if between 30 and 49 mL/min, and 4-6 days prior if less than 30 mL/min respectively.27

In regard to antiplatelet management, ASA and the P2Y12 receptor inhibitors (e.g. clopidogrel, prasugrel, and ticagrelor) are the most commonly utilized antiplatelets in patients undergoing endoscopic procedures. For patients who are on ASA monotherapy, whether 81 mg or 325 mg daily, for secondary cardiovascular prevention, no interruption of ASA therapy is necessary for elective procedures. The benefit of ASA for secondary cardiovascular prevention and the possible reduction in thrombotic events seen in RCTs of nonendoscopic surgical procedures is well known. However, there may be certain exceptions in which aspirin should be temporarily held. For example, short-term interruption of ASA could be considered in high risk procedures such as biliary or pancreatic sphincterotomy, ampullectomy, and peroral endoscopic myotomy. For patients on single antiplatelet therapy with a P2Y12 receptor inhibitor who are undergoing elective endoscopic GI procedures, the recent CAG/ACG guidelines did not provide a clear recommendation for or against temporary interruption of the P2Y12 receptor inhibitor. Although interruption of a P2Y12 receptor inhibitor should theoretically decrease a patient’s risk of bleeding, the available evidence reported a nonsignificant increased bleeding risk in patients who stop a P2Y12 receptor inhibitor for an elective endoscopic procedure compared with those who continue the medication.28,29 Therefore, until further data are available, for patients on P2Y12 receptor monotherapy, a reasonable strategy would be to temporarily hold therapy prior to high risk endoscopic procedures, assuming the patients are not at high cardiovascular risk. Clopidogrel and prasugrel have to be stopped 5-7 days prior to allow normal platelet aggregation to resume as opposed to ticagrelor, a reversible P2Y12 receptor inhibitor that can be stopped 3-5 days prior.30

Lastly, for patients who are on dual antiplatelet therapy (DAPT) for secondary prevention, continuation of ASA and temporary interruption of the P2Y12 receptor inhibitor is recommended while undergoing elective endoscopy. Studies have shown that those who discontinued both had a much higher incidence of stent thrombosis compared with those who remained on aspirin alone.4,28,31

 

 

Resumption of antithrombotic therapy after endoscopy

In general, antithrombotic therapy should be resumed upon completion of the procedure unless there remains a persistent risk of major bleeding.1,14 This consensus is based on studies available on warfarin and heparin products, with minimal literature available regarding the resumption of DOACs. The benefits of immediate re-initiation of antithrombotic therapy for the prevention of thromboembolic events should be weighed against the risk of hemorrhage associated with the specific agent, the time to onset of the medication, and procedure-specific circumstances. For the small subset of patients on warfarin with a high risk of thromboembolism (e.g., mechanical heart valve), bridging with LMWH should be started at the earliest possible time when there is no risk of major bleeding and continued until the international normalized ratio (INR) reaches a therapeutic level with warfarin. For patients at a lower risk of thromboembolism, warfarin should be restarted within 24 hours of the procedure. In addition, because of the shorter duration of DOACs, if treatment with these agents cannot resume within 24 hours of a high-risk procedure, bridge therapy should be considered with UFH or LMWH in patients with a high risk of thrombosis.18 In patients receiving DOACs for stroke prophylaxis in AF, the DOACS can be safely resumed 1 day after low-risk procedures and 2-3 days after high-risk procedures without the need for bridging.25 All antiplatelet agents should be resumed as soon as hemostasis is achieved.

Conclusion

Antithrombotic therapy is increasingly used given the aging population, widespread burden of cardiovascular comorbidities, and expanding indications for classes of medications such as direct oral anticoagulants. Given the association with antithrombotic medications and gastrointestinal bleeding, it is essential for gastroenterologists to understand the importance, necessity, and timing when holding these medications for endoscopic procedures. Even with the practice guidelines available today to help clinicians navigate certain situations, each patient’s antithrombotic management may be different, and communication with the prescribing physicians and including patients in the decision-making process is essential before planned procedures.

Dr. Wang is a gastroenterology fellow at the University of Chicago. Dr. Sengupta is an associate professor at the University of Chicago. They reported no funding or conflicts of interest.

 

 

References

1. ASGE Standards of Practice Committee, Acosta RD et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83(1):3-16.

2. Veitch AM et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Endoscopy. 2016;48(4):c1. doi: 10.1055/s-0042-122686.

3. Chan FKL et al. Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: Joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines. Gut. 2018;67(3):405-17.

4. Abraham NS 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. 2022;117(4):542-58.

5. Boustière C et al. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2011;43(5):445-61.

6. Fujimoto K et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc. 2014;26(1):1-14.

7. Wilke T et al. Patient preferences for oral anticoagulation therapy in atrial fibrillation: A systematic literature review. Patient 2017;10(1):17-37.

8. Gerson LB et al. Adverse events associated with anticoagulation therapy in the periendoscopic period. Gastrointest Endosc. 2010 Jun;71(7):1211-17.e2.

9. Horiuchi A et al. Removal of small colorectal polyps in anticoagulated patients: A prospective randomized comparison of cold snare and conventional polypectomy. Gastrointest Endosc 2014;79(3):417-23.

10. Lip GYH et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest. 2010;137(2):263-72.

11. 2012 Writing Committee Members, Jneid H et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (Updating the 2007 guideline and replacing the 2011 focused update): A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2012;126(7):875-910.

12. Douketis JD et al. Perioperative management of antithrombotic therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e326S-e350S.

13. Becker RC et al. Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures. J Am Coll Cardiol. 2009;54(24):2261-76.

14. Kwok A and Faigel DO. Management of anticoagulation before and after gastrointestinal endoscopy. Am J Gastroenterol. 2009;104(12):3085-97; quiz 3098.

15. Douketis JD et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373(9):823-33.

16. Kovacs MJ et al. Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): Double blind randomised controlled trial. BMJ 2021;373:n1205.

17. Tafur A and Douketis J. Perioperative management of anticoagulant and antiplatelet therapy. Heart 2018;104(17):1461-7.

18. Kato M et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment: 2017 appendix on anticoagulants including direct oral anticoagulants. Dig Endosc. 2018;30(4):433-40.

19. Inoue T et al. Clinical features of postpolypectomy bleeding associated with heparin bridge therapy. Dig Endosc. 2014;26(2):243-9.

20. Takeuchi Y et al. Continuous anticoagulation and cold snare polypectomy versus heparin bridging and hot snare polypectomy in patients on anticoagulants with subcentimeter polyps: A randomized controlled trial. Ann Intern Med. 2019;171(4):229-37.

21. Ara N et al. Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan. Dig Endosc. 2015;27(4):458-64.

22. Yanagisawa N et al. Postpolypectomy bleeding and thromboembolism risks associated with warfarin vs. direct oral anticoagulants. World J Gastroenterol. 2018;24(14):1540-9.

23. Arimoto J et al. Safety of cold snare polypectomy in patients receiving treatment with antithrombotic agents. Dig Dis Sci. 2019;64(11):3247-55.

24. Heublein V et al. Gastrointestinal endoscopy in patients receiving novel direct oral anticoagulants: Results from the prospective Dresden NOAC registry. J Gastroenterol. 2018;53(2):236-46.

25. Douketis JD et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med. 2019;179(11):1469-78.

26. Dubois V et al. Perioperative management of patients on direct oral anticoagulants. Thromb J. 2017;15:14.

27. Weitz JI et al. Periprocedural management and approach to bleeding in patients taking dabigatran. Circulation. 2012 Nov 13;126(20):2428-32.

28. Chan FKL et al. Risk of postpolypectomy bleeding with uninterrupted clopidogrel therapy in an industry-independent, double-blind, randomized trial. Gastroenterology. 2019;156(4):918-25.

29. Watanabe K et al. Effect of antiplatelet agent number, types, and pre-endoscopic management on postpolypectomy bleeding: Validation of endoscopy guidelines. Surg Endosc. 2021;35(1):317-25.

30. Gurbel PA et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: The ONSET/OFFSET study. Circulation. 2009;120(25):2577-85.

31. Eisenberg MJ et al. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation. 2009;119(12):1634-42.
 

Antithrombotic therapy is increasingly used to either reduce the risk of or treat thromboembolic episodes in patients with various medical conditions such as ischemic and valvular heart disease, atrial fibrillation (AF), cerebrovascular disease, peripheral arterial disease, venous thromboembolism (VTE) and hypercoagulable diseases. Antithrombotics include medications classified as anticoagulants or antiplatelets. Anticoagulants work by interfering with the native clotting cascade and consist of four main classes: vitamin K antagonists (VKA), heparin derivatives, direct factor Xa inhibitors, and direct thrombin inhibitors. Direct oral anticoagulants (DOACs) refer to dabigatran (a direct thrombin inhibitor) and the factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban).

Antiplatelets, on the other hand, work by decreasing platelet aggregation and thus preventing thrombus formation; they include P2Y12 receptor inhibitors, protease-activated receptor-1 inhibitors, glycoprotein IIb/IIIa receptor inhibitors, acetylsalicylic acid (ASA), and nonsteroidal anti-inflammatory drugs. All of these agents may directly cause or increase the risk of gastrointestinal (GI) bleeding from luminal sources such as ulcers or diverticula, as well as after endoscopic interventions such as polypectomy. However, there is also a risk of thromboembolic consequences if some of these agents are withheld. Thus, the management of patients receiving antithrombotic agents and undergoing GI endoscopy represents an important clinical challenge and something that every GI physician has to deal with routinely.

Dr. Wenfei Wang

The goal of this review is to discuss the optimal strategy for managing antithrombotics in patients undergoing elective endoscopy based on current available evidence and published clinical guidelines.1-4 Much of our discussion will review recommendations from the recently published joint American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guidelines on management of anticoagulants and antiplatelets in the periendoscopic period by Abraham et al.4

Factors that guide decision-making

The two most vital factors to consider prior to performing endoscopic procedures in patients receiving antithrombotic therapy are to assess the risk of bleeding associated with the procedure and to assess the risk of thromboembolism associated with the underlying medical condition for which the antithrombotic agents are being used. In addition, it is also important to keep in mind the individual characteristics of the antithrombotic agent(s) used when making these decisions.

Estimating procedure-related bleeding risk

Various endoscopic procedures have different risks of associated bleeding. Although guidelines from GI societies may differ when classifying procedures into low or high risk, it is important to know that most of the original data on postprocedural bleeding risks are from studies conducted in patients who are not on complex antithrombotic regimens and thus may not accurately reflect the bleeding risk of patients using newer antithrombotic therapies.1,4-7

Dr. Neil Sengupta

Traditionally, some of the common low-risk procedures have included diagnostic EGD and colonoscopy with or without biopsy, ERCP without sphincterotomy, biliary stent placement, and push or balloon-assisted enteroscopy. On the other hand, endoscopic procedures associated with interventions are known to have higher bleeding risk, and other procedural factors can influence this risk as well.8 For example, polypectomy, one of the most common interventions during endoscopy, is associated with bleeding risk ranging from 0.3% to 10% depending on multiple factors including polyp size, location, morphology (nonpolypoid, sessile, pedunculated), resection technique (cold or hot forceps, cold or hot snare), and type of cautery used.9 For some procedures, such as routine screening colonoscopy, however, the preprocedure estimate of bleeding risk can be uncertain because it is unclear if a high risk intervention (e.g., polypectomy of large polyp) will be necessary. For example, in the most recent ACG/CAG guidelines, colonoscopy with polypectomy < 1cm is considered a low/moderate risk bleeding procedure, whereas polypectomy > 1cm is considered high risk for bleeding.4 In these situations, the management of antithrombotic medications may depend on the individual patient’s risk of thrombosis and the specific antithrombotic agent. In the example of a patient undergoing colonoscopy while on antithrombotic medications, the bleeding risk associated with polypectomy can potentially be reduced by procedural techniques such as preferential use of cold snare polypectomy. Further high-quality data on the optimal procedural technique to reduce postpolypectomy bleeding in patients on antithrombotic medications is needed to help guide management.
 

 

 

Estimating thromboembolic risk

The risk of thromboembolic events in patients who are withholding their antithrombotic therapy for an endoscopic procedure depends on their underlying condition and individual characteristics. In patients who are on antithrombotic therapy for stroke prevention in non-valvular AF, the risk of cerebral thromboembolism in these patients is predictable using the CHA2DS2Vasc index.10 This scoring index includes heart failure, hypertension, age 75 years or older, diabetes mellitus, prior stroke or transient ischemic attack (TIA), vascular disease, age 65-74 years, and sex categories.

Patients with previous VTE on anticoagulation or those who have mechanical heart valves may have different risk factors for thromboembolic episodes. Among patients with VTE, time from initial VTE, history of recurrent VTE with antithrombotic interruption, and presence of underlying thrombophilia are most predictive of future thromboembolic risk. And for patients with mechanical heart valves, presence of a mitral valve prosthesis, and the presence or absence of associated heart failure and AF determine the annual risk of thromboembolic events. Bioprosthetic valves are generally considered low risk.

In patients with coronary artery disease (CAD), high thrombosis risk scenarios with holding antiplatelets include patients within 3 months of an acute coronary syndrome (ACS) event, within 6 months of a drug-eluting stent (DES) placement, or within 1 month of a bare metal coronary stent (BMS) placement. In addition, patients with ACS that occurred within the past 12 months of DES placement or within 2 months of BMS placement are also considered high risk.11,12 Even beyond these periods, certain patients may still be at high risk of stent occlusion. In particular, patients with a prior history of stent occlusion, ACS or ST elevation myocardial infection, prior multivessel percutaneous coronary intervention, diabetes, renal failure, or diffuse CAD are at higher risk of stent occlusion or ACS events with alteration of antithrombotic therapy.13 Thus, modification of antithrombotic regimens in these patients should be cautiously approached.
 

Management of antithrombotics prior to elective endoscopy

In patients who need elective endoscopic procedures, if the indication for antithrombotic therapy is short-term, the procedure is probably best delayed until after that period.13 For patients on long-term or lifelong antithrombotic treatment, the decision to temporarily hold the treatment for endoscopy should occur after a discussion with the patient and all of the involved providers. In some high-risk patients, these agents cannot be interrupted; therefore, clinicians must carefully weigh the risks and benefits of the procedure before proceeding with endoscopy. For patients who are known to be undergoing an elective endoscopic procedure, antithrombotic medications may or may not need to be held prior to the procedure depending on the type of therapy. For example, according to the recent ACG/CAG guidelines, warfarin should be continued, whereas DOACs should be temporarily stopped for patients who are undergoing elective/planned endoscopic GI procedures.

Unfractionated heparin (UFH) administered as a continuous intravenous infusion can generally be held 3-4 hours before the procedure, given its short half-life. Low molecular weight heparin (LMWH), including enoxaparin and dalteparin, should be stopped 24 hours prior to the procedure.2,14 Fondaparinux is a synthetic X-a inhibitor that requires discontinuation at least 36 hours preceding a high risk procedure. For patients on warfarin who are undergoing elective endoscopic procedures that are low risk for inducing bleeding, warfarin can be continued, as opposed to temporarily interrupted, although the dose should be omitted the morning of the procedure.4 For those who are undergoing high-risk endoscopic procedures (including colonoscopy with possible polypectomy > 1 cm), 5 days of temporary interruption without periprocedural bridging is appropriate in most patients. This is contrary to previous guidelines, which had recommended bridging for patients with a CHA2DS2Vasc score ≥ 2. Recent impactful randomized trials (BRIDGE and PERIOP-2) have called into question the benefit of periprocedural bridging with LMWH. Avoiding bridging anticoagulation was generally found to be similar to bridging in regard to prevention of thromboembolic complications, but importantly was associated with a decreased risk of major bleeding.15,16 Of note, periprocedural bridging may still be appropriate in a small subset of patients, including those with mechanical valves, AF with CHADS2 score > 5, and previous thromboembolism during temporary interruption of VKAs. The decision to bridge or not should ideally be made in a multidisciplinary fashion.15-20

Data are lacking on the ideal strategy for periendoscopic DOAC management. As mentioned above, for patients on DOACs who are undergoing elective endoscopic GI procedures, temporarily interrupting DOACs rather than continuing them is recommended. Currently, there are no randomized controlled trials addressing the management of DOACs in the periendoscopic period. However, based on five cohort studies, the ideal duration of DOAC interruption before endoscopic procedures may be between 1 and 2 days, excluding the day of the procedure.21-25 This strategy allows for a short preprocedural duration of DOAC interruption and likely provides a balance between bleeding and thromboembolism risk. Importantly, there are no reliable laboratory assays to assess the anticoagulant effect of DOACs, and an individual patient’s degree of renal dysfunction may impact how long the DOAC should be held. In general, the anti-Xa drugs should be held for 1-2 days if the creatinine clearance (CrCl) is ≥ 60 mL/min, for 3 days if the CrCl is between 30 mL/min and 59 mL/min, and for 4 days if the CrCl is less than 30 mL/min.26 For edoxaban, the recommendation is to hold at least 24 hours before high-risk procedures. The recommendation for stopping dabigatran is 2-3 days before a high-risk procedure in patients with CrCl more than 80 mL/min, 3-4 days prior if between 30 and 49 mL/min, and 4-6 days prior if less than 30 mL/min respectively.27

In regard to antiplatelet management, ASA and the P2Y12 receptor inhibitors (e.g. clopidogrel, prasugrel, and ticagrelor) are the most commonly utilized antiplatelets in patients undergoing endoscopic procedures. For patients who are on ASA monotherapy, whether 81 mg or 325 mg daily, for secondary cardiovascular prevention, no interruption of ASA therapy is necessary for elective procedures. The benefit of ASA for secondary cardiovascular prevention and the possible reduction in thrombotic events seen in RCTs of nonendoscopic surgical procedures is well known. However, there may be certain exceptions in which aspirin should be temporarily held. For example, short-term interruption of ASA could be considered in high risk procedures such as biliary or pancreatic sphincterotomy, ampullectomy, and peroral endoscopic myotomy. For patients on single antiplatelet therapy with a P2Y12 receptor inhibitor who are undergoing elective endoscopic GI procedures, the recent CAG/ACG guidelines did not provide a clear recommendation for or against temporary interruption of the P2Y12 receptor inhibitor. Although interruption of a P2Y12 receptor inhibitor should theoretically decrease a patient’s risk of bleeding, the available evidence reported a nonsignificant increased bleeding risk in patients who stop a P2Y12 receptor inhibitor for an elective endoscopic procedure compared with those who continue the medication.28,29 Therefore, until further data are available, for patients on P2Y12 receptor monotherapy, a reasonable strategy would be to temporarily hold therapy prior to high risk endoscopic procedures, assuming the patients are not at high cardiovascular risk. Clopidogrel and prasugrel have to be stopped 5-7 days prior to allow normal platelet aggregation to resume as opposed to ticagrelor, a reversible P2Y12 receptor inhibitor that can be stopped 3-5 days prior.30

Lastly, for patients who are on dual antiplatelet therapy (DAPT) for secondary prevention, continuation of ASA and temporary interruption of the P2Y12 receptor inhibitor is recommended while undergoing elective endoscopy. Studies have shown that those who discontinued both had a much higher incidence of stent thrombosis compared with those who remained on aspirin alone.4,28,31

 

 

Resumption of antithrombotic therapy after endoscopy

In general, antithrombotic therapy should be resumed upon completion of the procedure unless there remains a persistent risk of major bleeding.1,14 This consensus is based on studies available on warfarin and heparin products, with minimal literature available regarding the resumption of DOACs. The benefits of immediate re-initiation of antithrombotic therapy for the prevention of thromboembolic events should be weighed against the risk of hemorrhage associated with the specific agent, the time to onset of the medication, and procedure-specific circumstances. For the small subset of patients on warfarin with a high risk of thromboembolism (e.g., mechanical heart valve), bridging with LMWH should be started at the earliest possible time when there is no risk of major bleeding and continued until the international normalized ratio (INR) reaches a therapeutic level with warfarin. For patients at a lower risk of thromboembolism, warfarin should be restarted within 24 hours of the procedure. In addition, because of the shorter duration of DOACs, if treatment with these agents cannot resume within 24 hours of a high-risk procedure, bridge therapy should be considered with UFH or LMWH in patients with a high risk of thrombosis.18 In patients receiving DOACs for stroke prophylaxis in AF, the DOACS can be safely resumed 1 day after low-risk procedures and 2-3 days after high-risk procedures without the need for bridging.25 All antiplatelet agents should be resumed as soon as hemostasis is achieved.

Conclusion

Antithrombotic therapy is increasingly used given the aging population, widespread burden of cardiovascular comorbidities, and expanding indications for classes of medications such as direct oral anticoagulants. Given the association with antithrombotic medications and gastrointestinal bleeding, it is essential for gastroenterologists to understand the importance, necessity, and timing when holding these medications for endoscopic procedures. Even with the practice guidelines available today to help clinicians navigate certain situations, each patient’s antithrombotic management may be different, and communication with the prescribing physicians and including patients in the decision-making process is essential before planned procedures.

Dr. Wang is a gastroenterology fellow at the University of Chicago. Dr. Sengupta is an associate professor at the University of Chicago. They reported no funding or conflicts of interest.

 

 

References

1. ASGE Standards of Practice Committee, Acosta RD et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83(1):3-16.

2. Veitch AM et al. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Endoscopy. 2016;48(4):c1. doi: 10.1055/s-0042-122686.

3. Chan FKL et al. Management of patients on antithrombotic agents undergoing emergency and elective endoscopy: Joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines. Gut. 2018;67(3):405-17.

4. Abraham NS 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. 2022;117(4):542-58.

5. Boustière C et al. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2011;43(5):445-61.

6. Fujimoto K et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc. 2014;26(1):1-14.

7. Wilke T et al. Patient preferences for oral anticoagulation therapy in atrial fibrillation: A systematic literature review. Patient 2017;10(1):17-37.

8. Gerson LB et al. Adverse events associated with anticoagulation therapy in the periendoscopic period. Gastrointest Endosc. 2010 Jun;71(7):1211-17.e2.

9. Horiuchi A et al. Removal of small colorectal polyps in anticoagulated patients: A prospective randomized comparison of cold snare and conventional polypectomy. Gastrointest Endosc 2014;79(3):417-23.

10. Lip GYH et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The euro heart survey on atrial fibrillation. Chest. 2010;137(2):263-72.

11. 2012 Writing Committee Members, Jneid H et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (Updating the 2007 guideline and replacing the 2011 focused update): A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2012;126(7):875-910.

12. Douketis JD et al. Perioperative management of antithrombotic therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e326S-e350S.

13. Becker RC et al. Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures. J Am Coll Cardiol. 2009;54(24):2261-76.

14. Kwok A and Faigel DO. Management of anticoagulation before and after gastrointestinal endoscopy. Am J Gastroenterol. 2009;104(12):3085-97; quiz 3098.

15. Douketis JD et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373(9):823-33.

16. Kovacs MJ et al. Postoperative low molecular weight heparin bridging treatment for patients at high risk of arterial thromboembolism (PERIOP2): Double blind randomised controlled trial. BMJ 2021;373:n1205.

17. Tafur A and Douketis J. Perioperative management of anticoagulant and antiplatelet therapy. Heart 2018;104(17):1461-7.

18. Kato M et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment: 2017 appendix on anticoagulants including direct oral anticoagulants. Dig Endosc. 2018;30(4):433-40.

19. Inoue T et al. Clinical features of postpolypectomy bleeding associated with heparin bridge therapy. Dig Endosc. 2014;26(2):243-9.

20. Takeuchi Y et al. Continuous anticoagulation and cold snare polypectomy versus heparin bridging and hot snare polypectomy in patients on anticoagulants with subcentimeter polyps: A randomized controlled trial. Ann Intern Med. 2019;171(4):229-37.

21. Ara N et al. Prospective analysis of risk for bleeding after endoscopic biopsy without cessation of antithrombotics in Japan. Dig Endosc. 2015;27(4):458-64.

22. Yanagisawa N et al. Postpolypectomy bleeding and thromboembolism risks associated with warfarin vs. direct oral anticoagulants. World J Gastroenterol. 2018;24(14):1540-9.

23. Arimoto J et al. Safety of cold snare polypectomy in patients receiving treatment with antithrombotic agents. Dig Dis Sci. 2019;64(11):3247-55.

24. Heublein V et al. Gastrointestinal endoscopy in patients receiving novel direct oral anticoagulants: Results from the prospective Dresden NOAC registry. J Gastroenterol. 2018;53(2):236-46.

25. Douketis JD et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Intern Med. 2019;179(11):1469-78.

26. Dubois V et al. Perioperative management of patients on direct oral anticoagulants. Thromb J. 2017;15:14.

27. Weitz JI et al. Periprocedural management and approach to bleeding in patients taking dabigatran. Circulation. 2012 Nov 13;126(20):2428-32.

28. Chan FKL et al. Risk of postpolypectomy bleeding with uninterrupted clopidogrel therapy in an industry-independent, double-blind, randomized trial. Gastroenterology. 2019;156(4):918-25.

29. Watanabe K et al. Effect of antiplatelet agent number, types, and pre-endoscopic management on postpolypectomy bleeding: Validation of endoscopy guidelines. Surg Endosc. 2021;35(1):317-25.

30. Gurbel PA et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: The ONSET/OFFSET study. Circulation. 2009;120(25):2577-85.

31. Eisenberg MJ et al. Safety of short-term discontinuation of antiplatelet therapy in patients with drug-eluting stents. Circulation. 2009;119(12):1634-42.
 

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Adopting new evidence into practice – a guide for the new gastroenterologist

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Thu, 03/28/2019 - 14:38

The transition from gastroenterology fellowship to independent practice can be daunting. There may be concerns about procedural competency and increased levels of responsibility. Recent trainees have to manage their newly busy clinical schedules while trying to integrate evidence from a rapidly evolving landscape of medical literature into daily practice. Many recent graduates also are expected to participate in financial decisions or contribute to assessments about resource allocation regarding new technologies. These are challenges faced by those in both community and academic positions but may be more keenly felt in the first years of practice regardless of setting.

Dr. David A. Leiman

Without the benefit of experience, incorporating pertinent evidence from both within and outside of the field of gastroenterology as well as identifying disruptive technologies can be particularly difficult. There is scant guidance in this area, either during fellowship or from the existing literature1. Yet these are skills that, when properly developed, can be lifelong assets and, as a result, an evaluation of this process is warranted. Herein, we identify recent developments relevant to gastroenterologists to illustrate a conceptual framework for judging novel information.

A practical concern for the new gastroenterologist is learning to efficiently evaluate the merits of the latest research and then implement this knowledge in the clinic. Maintaining active society membership often includes access to scholarly journals. For example, AGA members receive Gastroenterology, Clinical Gastroenterology and Hepatology, and Cellular and Molecular Gastroenterology and Hepatology as part of their member benefits and have the opportunity to receive alerts when new content is published. Social media outlets such as Twitter and Facebook also simplify the process for readers to identify high-impact studies2 (see social media urls at the end of the story). In addition to reading, however, a critical review of these studies can prevent premature enthusiasm for modifying practice. The evolving evidence base for understanding proton pump inhibitor (PPI) risks is illustrative. Several studies attracted widespread media attention describing serious associated side effects, ranging from MI3 to dementia4 and stroke5. These studies were provocative but a decision to withhold PPIs from patients based on these concerns alone could lead to unintended consequences with poor outcomes. Ultimately, subsequent studies published only months later challenged these associations.6-8 Instead, thoughtful disclosure to patients of known risks and appropriate indications for PPI therapy based on resources such as the AGA Best Practice Advice9 is prudent. Reading more may be necessary but is insufficient; finding a forum to discuss novel research topics, such as in a monthly journal club10 or group practice meeting, can lead to stimulating discussion about how to apply pertinent research to change practice. The AGA Community is an excellent venue for this kind of interaction.

In many situations, keeping informed of updates about the risks and safety of medications prescribed by nongastroenterologists, particularly as they relate to GI conditions, can be even more difficult. A prime example of this is the rapidly expanding literature on indications and risks of direct oral anticoagulants. Rotating on the inpatient consultation service, with the chance to interact with multiple non-GI providers, affords an excellent opportunity to stay up to date. With the increased prevalence of atrial fibrillation as well as the potential expanded indications for direct oral anticoagulants based on recent randomized, controlled trials11,12, practicing gastroenterologists will be comanaging increasing numbers of patients hospitalized with gastrointestinal bleeding (GIB). Our understanding of the availability and indication for targeted reversal agents, such as idarucizumab, as well as nonspecific reversal agents, such as prothrombin complex concentrates, for those with life-threatening GIB is critical to optimal management of these patients. Multidisciplinary collaborations, such as with cardiogastroenterology clinics13, can be leveraged for optimal management of direct oral anticoagulants in the periendoscopy period.

Traditional outpatient consultative approaches are sometimes necessary but frequent reference to consensus societal guidelines on endoscopy in patients on antithrombotics14 should be made, particularly if they are printed and readily available in the ambulatory clinic and endoscopy suites. When information may be too new or sparse to utilize a national guideline, employing local data or experience to create a hospital-specific algorithm can ensure the delivery of high-quality, collaborative patient care.

Dr. Neil Sengupta

Much like reviewing the literature, evaluating new technologies poses its own challenges. Changes in clinical practice may be slow, as in the adoption of noninvasive methods for Barrett’s esophagus screening.15 But in an age when news of advances and updates in management spreads at tremendous speed through the use of social media, the ability to pivot or assimilate new discoveries and techniques will become increasingly relevant and important. A professional society’s endorsement can provide a framework for a decision, but other principles at play include sensible, critical analyses of the outcomes and costs as well as a balance of organizational and societal perspectives.16 The use of impedance planimetry is one such example. This is a relatively new technology, but it has received increasing interest recently.17 The first questions when considering adopting this type of device likely will be about its supporting evidence and the risk for causing harm. The pace of publications regarding its use for measuring esophageal distensibility has accelerated18. But good data does not necessarily translate into extensive uptake. Other important factors also are practical, e.g., whether a technology committee’s approval is needed and what is the learning curve, available technical support, need for capital purchases, reimbursement, etc. Functional luminal imaging probe (FLIP®) technology was developed to assess compliance in primary esophageal disorders and now has been applied to several other areas including anorectal disease, bariatric surgery, and therapeutic endoscopy19,20. Although seemingly a niche market, there is potential widespread application and an opportunity for collaborations that might not have been evident at first blush. Ultimately, any evaluation of new technology is to a certain extent speculation. Is the technology mature or novel? If it is the latter, this may provide a marketing advantage and facilitate a relationship that could lead to academic partnerships.

Embracing new devices and modifications to existing practice paradigms happens on a spectrum21. We are reminded of the maxim, “never be the first or last to adopt change.” One must be on the lookout for revolutionary or game-changing advances but be cautious to avoid irresponsible enthusiasm. Whether it is incorporating evidence from a recent study into everyday practice or judging the potential of new equipment, a balance must be achieved between detailed evaluation of the literature and understanding the practical consequences and feasibility of implementing change. Although these may be competing interests, achieving this is a pivotal step in success for the new gastroenterologist.

 

 

AGA journals' social media accounts



http://twitter.com/aga_gastro

http://twitter.com/aga_cgh

http://twitter.com/aga_cmgh

https://www.facebook.com/gastrojournal/

https://www.facebook.com/cghjournal/

https://www.facebook.com/cmghjournal/

 

References

1. Arora V et al. Closing the gap between internal medicine training and practice: Recommendations from recent graduates. Am J Med. 2005 Jun;118(6):685-7.

2. Gray DM et al. Making social media work for your practice. Clin Gastroenterol Hepatol. 2017 Nov;15:1651-4.

3. Shah NH et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One. 2015 Jun 10;10:e0124653.

4. Gomm W et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016 Apr;73(4):410-6.

5. Wang YF et al. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: A nationwide population-based study. Am J Gastroenterol. 2017 Jul;112:1084-93.

6. Nguyen LH et al. No significant association between proton pump inhibitor use and risk of stroke after adjustment for lifestyle factors and indication. Gastroenterology. 2018 Apr; 154(5):1290-7.

7. Lochhead P et al. Association between proton pump inhibitor use and cognitive function in women. Gastroenterology. 2017 Oct;153(4):971-9.

8. Landi SN et al. No increase in risk of acute myocardial infarction in privately insured adults prescribed proton pump inhibitors vs histamine-2 receptor antagonists (2002-2014). Gastroenterology 2018 Mar;154(4):861-73.

9. Freedberg DE et al. The risks and benefits of long-term use of proton pump inhibitors: Expert review and best practice advise from the American Gastroenterological Association. Gastroenterology. 2017 Mar;152:706-15.

10. Judd S et al. Approach to presenting a clinical journal club. Gastroenterology. 2014 Jun;146(7):1591-3.

11. Weitz JI et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376:1211-22.

12. Eikelboom JW et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017 Oct. 5;377:1319-30.

13. Abraham NS. Novel oral anticoagulants and gastrointestinal bleeding: a case for cardiogastroenterology. Clin Gastroenterol Hepatol. 2013;11(4):324-8.

14. Acosta RD et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83:3-16.

15. Sami SS et al. Screening for Barrett’s esophagus and esophageal adenocarcinoma: rationale, recent progress, challenges and future directions. Clin Gastroenterol Hepatol. 2015 Apr;13:623-34.

16. Laupacis A et al. How attractive does a new technology need to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ. 1992 Feb 15;146:473-81.

17. Hirano I et al. Functional lumen imaging probe for the management of esophageal disorders: Expert review from the clinical practice updates committee of the AGA Institute. Clin Gastroenterol Hepatol. 2017 Mar;15:325-34.

18. Kwiatek MA et al. Esophagogastric junction distensibility assessed with an endoscopic functional luminal imaging probe (EndoFLIP). Gastrointest Endosc. 2010 Aug;72:272-82.

19. Leroi AM et al. The diagnostic value of the functional lumen imaging probe versus high-resolution anorectal manometry in patients with fecal incontinence. Neurogastroenterol Motil. 2018 Jan 18; doi: 10.1111/nmo.13291.

20. Reynolds JL et al. Intraoperative assessment of the effects of laparoscopic sleeve gastrectomy on the distensibility of the lower esophageal sphincter using impedance planimetry. Surg Endosc. 2016 Nov;30:4904-9.

21. Aisenberg J. Optical biopsy for colorectal polyps: moving along the S-shaped curve. Gastrointest Endosc. 2014 Mar;79:399-401.

Dr. Leiman, assistant professor of medicine, division of gastroenterology, Duke University, Durham, N.C.; Dr. Sengupta, assistant professor of medicine, section of gastroenterology, hepatology, and nutrition, University of Chicago Medical Center.

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The transition from gastroenterology fellowship to independent practice can be daunting. There may be concerns about procedural competency and increased levels of responsibility. Recent trainees have to manage their newly busy clinical schedules while trying to integrate evidence from a rapidly evolving landscape of medical literature into daily practice. Many recent graduates also are expected to participate in financial decisions or contribute to assessments about resource allocation regarding new technologies. These are challenges faced by those in both community and academic positions but may be more keenly felt in the first years of practice regardless of setting.

Dr. David A. Leiman

Without the benefit of experience, incorporating pertinent evidence from both within and outside of the field of gastroenterology as well as identifying disruptive technologies can be particularly difficult. There is scant guidance in this area, either during fellowship or from the existing literature1. Yet these are skills that, when properly developed, can be lifelong assets and, as a result, an evaluation of this process is warranted. Herein, we identify recent developments relevant to gastroenterologists to illustrate a conceptual framework for judging novel information.

A practical concern for the new gastroenterologist is learning to efficiently evaluate the merits of the latest research and then implement this knowledge in the clinic. Maintaining active society membership often includes access to scholarly journals. For example, AGA members receive Gastroenterology, Clinical Gastroenterology and Hepatology, and Cellular and Molecular Gastroenterology and Hepatology as part of their member benefits and have the opportunity to receive alerts when new content is published. Social media outlets such as Twitter and Facebook also simplify the process for readers to identify high-impact studies2 (see social media urls at the end of the story). In addition to reading, however, a critical review of these studies can prevent premature enthusiasm for modifying practice. The evolving evidence base for understanding proton pump inhibitor (PPI) risks is illustrative. Several studies attracted widespread media attention describing serious associated side effects, ranging from MI3 to dementia4 and stroke5. These studies were provocative but a decision to withhold PPIs from patients based on these concerns alone could lead to unintended consequences with poor outcomes. Ultimately, subsequent studies published only months later challenged these associations.6-8 Instead, thoughtful disclosure to patients of known risks and appropriate indications for PPI therapy based on resources such as the AGA Best Practice Advice9 is prudent. Reading more may be necessary but is insufficient; finding a forum to discuss novel research topics, such as in a monthly journal club10 or group practice meeting, can lead to stimulating discussion about how to apply pertinent research to change practice. The AGA Community is an excellent venue for this kind of interaction.

In many situations, keeping informed of updates about the risks and safety of medications prescribed by nongastroenterologists, particularly as they relate to GI conditions, can be even more difficult. A prime example of this is the rapidly expanding literature on indications and risks of direct oral anticoagulants. Rotating on the inpatient consultation service, with the chance to interact with multiple non-GI providers, affords an excellent opportunity to stay up to date. With the increased prevalence of atrial fibrillation as well as the potential expanded indications for direct oral anticoagulants based on recent randomized, controlled trials11,12, practicing gastroenterologists will be comanaging increasing numbers of patients hospitalized with gastrointestinal bleeding (GIB). Our understanding of the availability and indication for targeted reversal agents, such as idarucizumab, as well as nonspecific reversal agents, such as prothrombin complex concentrates, for those with life-threatening GIB is critical to optimal management of these patients. Multidisciplinary collaborations, such as with cardiogastroenterology clinics13, can be leveraged for optimal management of direct oral anticoagulants in the periendoscopy period.

Traditional outpatient consultative approaches are sometimes necessary but frequent reference to consensus societal guidelines on endoscopy in patients on antithrombotics14 should be made, particularly if they are printed and readily available in the ambulatory clinic and endoscopy suites. When information may be too new or sparse to utilize a national guideline, employing local data or experience to create a hospital-specific algorithm can ensure the delivery of high-quality, collaborative patient care.

Dr. Neil Sengupta

Much like reviewing the literature, evaluating new technologies poses its own challenges. Changes in clinical practice may be slow, as in the adoption of noninvasive methods for Barrett’s esophagus screening.15 But in an age when news of advances and updates in management spreads at tremendous speed through the use of social media, the ability to pivot or assimilate new discoveries and techniques will become increasingly relevant and important. A professional society’s endorsement can provide a framework for a decision, but other principles at play include sensible, critical analyses of the outcomes and costs as well as a balance of organizational and societal perspectives.16 The use of impedance planimetry is one such example. This is a relatively new technology, but it has received increasing interest recently.17 The first questions when considering adopting this type of device likely will be about its supporting evidence and the risk for causing harm. The pace of publications regarding its use for measuring esophageal distensibility has accelerated18. But good data does not necessarily translate into extensive uptake. Other important factors also are practical, e.g., whether a technology committee’s approval is needed and what is the learning curve, available technical support, need for capital purchases, reimbursement, etc. Functional luminal imaging probe (FLIP®) technology was developed to assess compliance in primary esophageal disorders and now has been applied to several other areas including anorectal disease, bariatric surgery, and therapeutic endoscopy19,20. Although seemingly a niche market, there is potential widespread application and an opportunity for collaborations that might not have been evident at first blush. Ultimately, any evaluation of new technology is to a certain extent speculation. Is the technology mature or novel? If it is the latter, this may provide a marketing advantage and facilitate a relationship that could lead to academic partnerships.

Embracing new devices and modifications to existing practice paradigms happens on a spectrum21. We are reminded of the maxim, “never be the first or last to adopt change.” One must be on the lookout for revolutionary or game-changing advances but be cautious to avoid irresponsible enthusiasm. Whether it is incorporating evidence from a recent study into everyday practice or judging the potential of new equipment, a balance must be achieved between detailed evaluation of the literature and understanding the practical consequences and feasibility of implementing change. Although these may be competing interests, achieving this is a pivotal step in success for the new gastroenterologist.

 

 

AGA journals' social media accounts



http://twitter.com/aga_gastro

http://twitter.com/aga_cgh

http://twitter.com/aga_cmgh

https://www.facebook.com/gastrojournal/

https://www.facebook.com/cghjournal/

https://www.facebook.com/cmghjournal/

 

References

1. Arora V et al. Closing the gap between internal medicine training and practice: Recommendations from recent graduates. Am J Med. 2005 Jun;118(6):685-7.

2. Gray DM et al. Making social media work for your practice. Clin Gastroenterol Hepatol. 2017 Nov;15:1651-4.

3. Shah NH et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One. 2015 Jun 10;10:e0124653.

4. Gomm W et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016 Apr;73(4):410-6.

5. Wang YF et al. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: A nationwide population-based study. Am J Gastroenterol. 2017 Jul;112:1084-93.

6. Nguyen LH et al. No significant association between proton pump inhibitor use and risk of stroke after adjustment for lifestyle factors and indication. Gastroenterology. 2018 Apr; 154(5):1290-7.

7. Lochhead P et al. Association between proton pump inhibitor use and cognitive function in women. Gastroenterology. 2017 Oct;153(4):971-9.

8. Landi SN et al. No increase in risk of acute myocardial infarction in privately insured adults prescribed proton pump inhibitors vs histamine-2 receptor antagonists (2002-2014). Gastroenterology 2018 Mar;154(4):861-73.

9. Freedberg DE et al. The risks and benefits of long-term use of proton pump inhibitors: Expert review and best practice advise from the American Gastroenterological Association. Gastroenterology. 2017 Mar;152:706-15.

10. Judd S et al. Approach to presenting a clinical journal club. Gastroenterology. 2014 Jun;146(7):1591-3.

11. Weitz JI et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376:1211-22.

12. Eikelboom JW et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017 Oct. 5;377:1319-30.

13. Abraham NS. Novel oral anticoagulants and gastrointestinal bleeding: a case for cardiogastroenterology. Clin Gastroenterol Hepatol. 2013;11(4):324-8.

14. Acosta RD et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83:3-16.

15. Sami SS et al. Screening for Barrett’s esophagus and esophageal adenocarcinoma: rationale, recent progress, challenges and future directions. Clin Gastroenterol Hepatol. 2015 Apr;13:623-34.

16. Laupacis A et al. How attractive does a new technology need to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ. 1992 Feb 15;146:473-81.

17. Hirano I et al. Functional lumen imaging probe for the management of esophageal disorders: Expert review from the clinical practice updates committee of the AGA Institute. Clin Gastroenterol Hepatol. 2017 Mar;15:325-34.

18. Kwiatek MA et al. Esophagogastric junction distensibility assessed with an endoscopic functional luminal imaging probe (EndoFLIP). Gastrointest Endosc. 2010 Aug;72:272-82.

19. Leroi AM et al. The diagnostic value of the functional lumen imaging probe versus high-resolution anorectal manometry in patients with fecal incontinence. Neurogastroenterol Motil. 2018 Jan 18; doi: 10.1111/nmo.13291.

20. Reynolds JL et al. Intraoperative assessment of the effects of laparoscopic sleeve gastrectomy on the distensibility of the lower esophageal sphincter using impedance planimetry. Surg Endosc. 2016 Nov;30:4904-9.

21. Aisenberg J. Optical biopsy for colorectal polyps: moving along the S-shaped curve. Gastrointest Endosc. 2014 Mar;79:399-401.

Dr. Leiman, assistant professor of medicine, division of gastroenterology, Duke University, Durham, N.C.; Dr. Sengupta, assistant professor of medicine, section of gastroenterology, hepatology, and nutrition, University of Chicago Medical Center.

The transition from gastroenterology fellowship to independent practice can be daunting. There may be concerns about procedural competency and increased levels of responsibility. Recent trainees have to manage their newly busy clinical schedules while trying to integrate evidence from a rapidly evolving landscape of medical literature into daily practice. Many recent graduates also are expected to participate in financial decisions or contribute to assessments about resource allocation regarding new technologies. These are challenges faced by those in both community and academic positions but may be more keenly felt in the first years of practice regardless of setting.

Dr. David A. Leiman

Without the benefit of experience, incorporating pertinent evidence from both within and outside of the field of gastroenterology as well as identifying disruptive technologies can be particularly difficult. There is scant guidance in this area, either during fellowship or from the existing literature1. Yet these are skills that, when properly developed, can be lifelong assets and, as a result, an evaluation of this process is warranted. Herein, we identify recent developments relevant to gastroenterologists to illustrate a conceptual framework for judging novel information.

A practical concern for the new gastroenterologist is learning to efficiently evaluate the merits of the latest research and then implement this knowledge in the clinic. Maintaining active society membership often includes access to scholarly journals. For example, AGA members receive Gastroenterology, Clinical Gastroenterology and Hepatology, and Cellular and Molecular Gastroenterology and Hepatology as part of their member benefits and have the opportunity to receive alerts when new content is published. Social media outlets such as Twitter and Facebook also simplify the process for readers to identify high-impact studies2 (see social media urls at the end of the story). In addition to reading, however, a critical review of these studies can prevent premature enthusiasm for modifying practice. The evolving evidence base for understanding proton pump inhibitor (PPI) risks is illustrative. Several studies attracted widespread media attention describing serious associated side effects, ranging from MI3 to dementia4 and stroke5. These studies were provocative but a decision to withhold PPIs from patients based on these concerns alone could lead to unintended consequences with poor outcomes. Ultimately, subsequent studies published only months later challenged these associations.6-8 Instead, thoughtful disclosure to patients of known risks and appropriate indications for PPI therapy based on resources such as the AGA Best Practice Advice9 is prudent. Reading more may be necessary but is insufficient; finding a forum to discuss novel research topics, such as in a monthly journal club10 or group practice meeting, can lead to stimulating discussion about how to apply pertinent research to change practice. The AGA Community is an excellent venue for this kind of interaction.

In many situations, keeping informed of updates about the risks and safety of medications prescribed by nongastroenterologists, particularly as they relate to GI conditions, can be even more difficult. A prime example of this is the rapidly expanding literature on indications and risks of direct oral anticoagulants. Rotating on the inpatient consultation service, with the chance to interact with multiple non-GI providers, affords an excellent opportunity to stay up to date. With the increased prevalence of atrial fibrillation as well as the potential expanded indications for direct oral anticoagulants based on recent randomized, controlled trials11,12, practicing gastroenterologists will be comanaging increasing numbers of patients hospitalized with gastrointestinal bleeding (GIB). Our understanding of the availability and indication for targeted reversal agents, such as idarucizumab, as well as nonspecific reversal agents, such as prothrombin complex concentrates, for those with life-threatening GIB is critical to optimal management of these patients. Multidisciplinary collaborations, such as with cardiogastroenterology clinics13, can be leveraged for optimal management of direct oral anticoagulants in the periendoscopy period.

Traditional outpatient consultative approaches are sometimes necessary but frequent reference to consensus societal guidelines on endoscopy in patients on antithrombotics14 should be made, particularly if they are printed and readily available in the ambulatory clinic and endoscopy suites. When information may be too new or sparse to utilize a national guideline, employing local data or experience to create a hospital-specific algorithm can ensure the delivery of high-quality, collaborative patient care.

Dr. Neil Sengupta

Much like reviewing the literature, evaluating new technologies poses its own challenges. Changes in clinical practice may be slow, as in the adoption of noninvasive methods for Barrett’s esophagus screening.15 But in an age when news of advances and updates in management spreads at tremendous speed through the use of social media, the ability to pivot or assimilate new discoveries and techniques will become increasingly relevant and important. A professional society’s endorsement can provide a framework for a decision, but other principles at play include sensible, critical analyses of the outcomes and costs as well as a balance of organizational and societal perspectives.16 The use of impedance planimetry is one such example. This is a relatively new technology, but it has received increasing interest recently.17 The first questions when considering adopting this type of device likely will be about its supporting evidence and the risk for causing harm. The pace of publications regarding its use for measuring esophageal distensibility has accelerated18. But good data does not necessarily translate into extensive uptake. Other important factors also are practical, e.g., whether a technology committee’s approval is needed and what is the learning curve, available technical support, need for capital purchases, reimbursement, etc. Functional luminal imaging probe (FLIP®) technology was developed to assess compliance in primary esophageal disorders and now has been applied to several other areas including anorectal disease, bariatric surgery, and therapeutic endoscopy19,20. Although seemingly a niche market, there is potential widespread application and an opportunity for collaborations that might not have been evident at first blush. Ultimately, any evaluation of new technology is to a certain extent speculation. Is the technology mature or novel? If it is the latter, this may provide a marketing advantage and facilitate a relationship that could lead to academic partnerships.

Embracing new devices and modifications to existing practice paradigms happens on a spectrum21. We are reminded of the maxim, “never be the first or last to adopt change.” One must be on the lookout for revolutionary or game-changing advances but be cautious to avoid irresponsible enthusiasm. Whether it is incorporating evidence from a recent study into everyday practice or judging the potential of new equipment, a balance must be achieved between detailed evaluation of the literature and understanding the practical consequences and feasibility of implementing change. Although these may be competing interests, achieving this is a pivotal step in success for the new gastroenterologist.

 

 

AGA journals' social media accounts



http://twitter.com/aga_gastro

http://twitter.com/aga_cgh

http://twitter.com/aga_cmgh

https://www.facebook.com/gastrojournal/

https://www.facebook.com/cghjournal/

https://www.facebook.com/cmghjournal/

 

References

1. Arora V et al. Closing the gap between internal medicine training and practice: Recommendations from recent graduates. Am J Med. 2005 Jun;118(6):685-7.

2. Gray DM et al. Making social media work for your practice. Clin Gastroenterol Hepatol. 2017 Nov;15:1651-4.

3. Shah NH et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One. 2015 Jun 10;10:e0124653.

4. Gomm W et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016 Apr;73(4):410-6.

5. Wang YF et al. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: A nationwide population-based study. Am J Gastroenterol. 2017 Jul;112:1084-93.

6. Nguyen LH et al. No significant association between proton pump inhibitor use and risk of stroke after adjustment for lifestyle factors and indication. Gastroenterology. 2018 Apr; 154(5):1290-7.

7. Lochhead P et al. Association between proton pump inhibitor use and cognitive function in women. Gastroenterology. 2017 Oct;153(4):971-9.

8. Landi SN et al. No increase in risk of acute myocardial infarction in privately insured adults prescribed proton pump inhibitors vs histamine-2 receptor antagonists (2002-2014). Gastroenterology 2018 Mar;154(4):861-73.

9. Freedberg DE et al. The risks and benefits of long-term use of proton pump inhibitors: Expert review and best practice advise from the American Gastroenterological Association. Gastroenterology. 2017 Mar;152:706-15.

10. Judd S et al. Approach to presenting a clinical journal club. Gastroenterology. 2014 Jun;146(7):1591-3.

11. Weitz JI et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017 Mar 30;376:1211-22.

12. Eikelboom JW et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017 Oct. 5;377:1319-30.

13. Abraham NS. Novel oral anticoagulants and gastrointestinal bleeding: a case for cardiogastroenterology. Clin Gastroenterol Hepatol. 2013;11(4):324-8.

14. Acosta RD et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc. 2016;83:3-16.

15. Sami SS et al. Screening for Barrett’s esophagus and esophageal adenocarcinoma: rationale, recent progress, challenges and future directions. Clin Gastroenterol Hepatol. 2015 Apr;13:623-34.

16. Laupacis A et al. How attractive does a new technology need to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ. 1992 Feb 15;146:473-81.

17. Hirano I et al. Functional lumen imaging probe for the management of esophageal disorders: Expert review from the clinical practice updates committee of the AGA Institute. Clin Gastroenterol Hepatol. 2017 Mar;15:325-34.

18. Kwiatek MA et al. Esophagogastric junction distensibility assessed with an endoscopic functional luminal imaging probe (EndoFLIP). Gastrointest Endosc. 2010 Aug;72:272-82.

19. Leroi AM et al. The diagnostic value of the functional lumen imaging probe versus high-resolution anorectal manometry in patients with fecal incontinence. Neurogastroenterol Motil. 2018 Jan 18; doi: 10.1111/nmo.13291.

20. Reynolds JL et al. Intraoperative assessment of the effects of laparoscopic sleeve gastrectomy on the distensibility of the lower esophageal sphincter using impedance planimetry. Surg Endosc. 2016 Nov;30:4904-9.

21. Aisenberg J. Optical biopsy for colorectal polyps: moving along the S-shaped curve. Gastrointest Endosc. 2014 Mar;79:399-401.

Dr. Leiman, assistant professor of medicine, division of gastroenterology, Duke University, Durham, N.C.; Dr. Sengupta, assistant professor of medicine, section of gastroenterology, hepatology, and nutrition, University of Chicago Medical Center.

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