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.

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

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.

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

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.

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

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.
 

Dear colleagues,

Innovation is the livelihood of our field, driving major advances in endoscopy and attracting many of us to Gastroenterology. From the development of endoscopic retrograde cholangiopancreatography to the wide-spread adoption of third space endoscopy, we continue to push the boundaries of our practice. But what is the next big disruption in GI, and how will it impact us? In this issue of Perspectives, two experts present their thoughts on current hot topics in GI. Dr. Jeremy Glissen Brown discusses the application of artificial intelligence in GI highlighting its promise but also raising important questions. Dr. Raman Muthusamy elaborates on single-use endoscopes – are they the wave of the future in preventing infection and meeting patient preference? Or will their long-term cost and environmental impact limit their use? I welcome your own thoughts on disruptive innovation in Gastroenterology – share with us on Twitter @AGA_GIHN and by email at [email protected].

Gyanprakash A. Ketwaroo, MD, MSc, is an associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

The AI revolution, with some important caveats

BY JEREMY R. GLISSEN BROWN, MD, MSC

In 2018, Japan’s Pharmaceutical and Medical Device Agency approved the first artificial intelligence (AI)–based tool, a computer-aided diagnosis system (CADx) for use in clinical practice.¹ Since that time, we have seen regulatory approval for a variety of deep learning and AI-based tools in endoscopy and beyond. In addition, there has been an enormous amount of commercial and research interest in AI-based tools in clinical medicine and gastroenterology, and it is almost impossible to open a major gastroenterology journal or go to an academic conference without encountering a slew of AI-based projects.

Many thought and industry leaders say that we are in the midst of an AI revolution in gastroenterology. Indeed, we are at a period of unprecedented growth for deep learning and AI for several reasons, including a recent shift toward data-driven approaches, advancement of machine-learning techniques, and increased computing power. There is, however, also an unprecedented amount of scrutiny and thoughtful conversation about the role AI might play in clinical practice and how we use and regulate these tools in the clinical setting. We are thus in a unique position to ask ourselves the essential question: “Are we on the cusp of an AI revolution in gastroenterology, or are we seeing the release of medical software that is perhaps at best useful in a niche environment and at worse a hype-driven novelty without much clinical benefit?” We will use the most popular use-case, computer aided detection (CADe) of polyps in the colon, to explore this question. In the end, I believe that deep-learning technology will fundamentally change the way we practice gastroenterology. However, this is the perfect time to explore what this means now, and what we can do to shape what it will mean for the future.

CADe: Promise and questions

CADe is a computer vision task that involves localization, such as finding a polyp during colonoscopy and highlighting it with a hollow box. CADe in colonoscopy is perhaps the most well-studied application of deep learning in GI endoscopy to date and is furthest along in the development-implementation pipeline. Because of this, it is an ideal use-case for examining both the evidence that currently supports its use as well as the questions that have come up as we are starting to see CADe algorithms deployed in clinical practice. It is honestly astounding to think that, just 5 years ago, we were talking about CADe as a research concept. While early efforts applying traditional machine learning date back at least to the 1990s, we started to see prospective studies of CADe systems with undetectable or nearly undetectable latency in 2019.² Since that time we have seen the publication of at least 10 randomized clinical trials involving CADe.

CADe clearly has an impact on some of the conventional quality metrics we use for colonoscopy. While there is considerable heterogeneity in region and design among these trials, most show a significant increase in adenoma detection rate (ADR) and adenomas per colonoscopy. Tandem studies show decreases in adenoma miss rate, and at least one study showed a decrease in sessile serrated lesion miss rate as well. In one of the first randomized, controlled trials across multiple endoscopy centers in Italy, Repici and colleagues showed an increase in ADR from 40.4% in the control group to 54.8% in the CADe group (RR, 1.30; 95% confidence interval, 1.14-1.45).3 Because of pioneering trials such as this one, there are currently several CADe systems that have received regulatory approval in Europe, Asia, and the United States and are being deployed commercially.

It is also clear that the technology is there. In clinical practice, the Food and Drug Administration–approved systems work smoothly, with little to no detectable latency and generally low false-positive and false-negative rates. With clinical deployment, however, we have seen the emergence of healthy debate surrounding every aspect of this task-specific AI. On the development side, important questions include transparency of development data, ensuring that algorithm development is ethical and equitable (as deep learning is susceptible to exacerbating human biases) and methods of data labeling. On the deployment level, important concerns include proper regulation of locked versus “open” algorithms and downstream effects on cost.

In addition, with CADe we have seen a variety of clinical questions crop up because of the novelty of the technology. These include the concern that the increase in ADR we have seen thus far is driven in large part by diminutive and small adenomas (with healthy debate in turn as to these entities’ influence on interval colorectal cancer rates), the effect CADe might have on fellowship training to detect polyps with the human eye, and whether the technology affects sessile serrated lesion detection rates or not. The great thing about such questions is that they have inspired novel research related to CADe in the clinical setting, including how CADe affects trainee ADR, how CADe affects gaze patterns, and how CADe affects recommended surveillance intervals.

CADx, novel applications, and the future

Though there is not space to expand in this particular forum, it is safe to say that with the advancement of CADx in endoscopy and colonoscopy, we have seen similar and novel questions come up. The beautiful thing about all of this is that we are just scratching the surface of what is achievable with deep learning. We have started to see novel projects utilizing deep-learning algorithms, from detecting cirrhosis on ECG to automatically classifying stool consistency on the Bristol Stool Scale from pictures of stool. I ultimately do think that the deployment of AI tools will fundamentally change the way we practice and think about gastroenterology. We are at an incredibly exciting time where we as physicians have the power to shape what that looks like, how we think about AI deployment and regulation and where we go from here.

Dr. Glissen Brown is with the division of gastroenterology and hepatology at Duke University Medical Center, Durham, N.C. He has served as a consultant for Medtronic.

References

1. Aisu N et al. PLOS Digital Health. 2021 Jan 18. doi: 10.1371/journal.pdig.0000001.

2. Wang P et al. Gut. 2019 Oct;68(10):1813-9.

3. Repici A et al. Gastroenterology. 2020 Aug;159(2):512-20.e7.

What’s the future of single-use endoscopes?

BY V. RAMAN MUTHUSAMY, MD, MAS

Single-use endoscopes have been proposed as a definitive solution to the risk of endoscope-transmitted infections. While these infections have been reported for several decades, they have traditionally been associated with identified breaches in the reprocessing protocol. In 2015, numerous cases of duodenoscope-transmitted infections were reported after endoscopic retrograde cholangiopancreatography (ERCP) procedures. Many, if not most, of these cases were not associated with identified deviations from standard high-level disinfection protocols and occurred at high-volume experienced facilities. A subsequent FDA postmarket surveillance study found contamination rates were linked with potentially pathogenic bacteria in approximately 5% of duodenoscopes. Thus, amid growing concerns about the ability to adequately clean these complex devices, these events prompted the development of single-use duodenoscopes. Given the multifactorial causes leading to contaminated duodenoscopes, the advantages of such single-use devices are their ability to ensure the elimination of the potential of infection transmission as these devices are never reused. In addition to this primary benefit, the ability to create single-use devices could lead to more easily available specialty scopes and allow variations in endoscope design that could improve ergonomics. Single-use devices may also expand the ability to provide endoscopic services by eliminating the need for device reprocessing equipment at low-volume sites. However, several concerns have been raised regarding their use, especially if it were to become widespread. These include issues of device quality and performance (potentially leading to more failed cases or adverse events), cost, their environmental impact and current uncertainty regarding their indications for use. Furthermore, new alternatives such as reusable devices with partially disposable components or future low-temperature sterilization options may minimize the need for such devices. We will briefly discuss these issues in more detail below.

Given that nearly all cases of GI device–transmitted infections where standard reprocessing protocols were followed have occurred in duodenoscopes, I will focus on single-use duodenoscopes in this article. It is important that we reassure our patients and colleagues that standard reprocessing appears to be extremely effective with all other types of devices, including elevator containing linear echoendoscopes. Studies investigating the causes of why duodenoscopes have primarily been associated with device-transmitted outbreaks have focused on the complexity of the elevator including its recesses, fixed end-cap and wire channels. However, culturing has shown that up to one-third of contamination may occur in the instrument channels or in the region of the biopsy cap, leading to some potential residual sites of infection even when newly developed reusable devices with disposable elevators/end-caps are utilized.¹ Another challenge with reprocessing is the ability to prove residual contamination does not exist. While culturing the devices after reprocessing is most used, it should be noted many sites with outbreaks failed to culture the culprit bacteria from the devices as accessing the sites of contamination can be challenging. The use of other markers of residual contamination such as ATP and tests for residual blood/protein have yielded variable results. Specifically, ATP testing has not correlated well with culture results but may be helpful in assessing the quality of manual cleaning.²

These challenges have made the concept of single-use devices more appealing given the lack of a need reprocess devices or validate cleaning efficacy. Currently, there are two FDA-approved devices on the market, but the published literature to date has largely involved one of these devices. To date, in four published studies that have assessed the clinical performance of single-use duodenoscopes in over 400 patients, procedural success rates have ranged from 91% to 97% with adverse event rates and endoscopist satisfaction scores comparable to reusable devices. Most of these users were expert biliary endoscopists and more data are needed regarding the performance of the device in lower-volume and nonexpert users. While indications for use in these studies have varied, I feel that there are four potential scenarios to utilize these devices: in patients with known multidrug-resistant organisms undergoing ERCP; to facilitate logistics/operations when a reusable device is not available; in critically ill patients who would not tolerate a scope-acquired infection; and in procedures associated with a risk of bacteremia.

While preliminary data suggest single-use duodenoscopes are safe and effective in expert hands, concerns exist regarding their implementation more broadly into clinical practice. First, the devices cost between $1,500-3,000, making them impractical for many health systems. One study estimated the break-even cost of the device to be $800-1,300 based on variation in site volume and device contamination rates.³ However, it should be noted that current enhanced reprocessing protocols for reusable devices may add an additional $75,000-$400,000 per year based on center volume.⁴ In the United States, there is currently payment by federal and some commercial payors that cover part or all of the device cost, but whether this will continue long-term is unclear. In addition, there is significant concern regarding the environmental impact of a broader mover to single-use devices. Reprocessing programs do exist for these devices, but detailed analyses regarding the environmental effects of a strategy using single-use versus reusable devices and the waste generated from each are needed.

Finally, while primarily created to avoid device-related infection transmission, other benefits can be realized with single-use devices. The potential for ergonomic enhancements (variable handle sizes or shaft stiffness, R- and L-handed scopes) as well as the creation of specialty devices (extra-long or thin devices, devices with special optical or rotational capabilities) may become more feasible with a single-use platform. Finally, the pace of endoscopic innovation and refinement is likely to quicken with a single use platform, and new advancements can be incorporated in a timelier manner.

Conclusion

In summary, I believe single-use devices offer the potential to improve the safety of endoscopic procedures as well as improve procedural access, enhance ergonomics, and foster and expedite device innovation. However, reductions in cost, refining their indications, and developing recycling programs to minimize their environmental impact will be essential before more widespread adoption is achieved.

Dr. Muthusamy is a professor of clinical medicine at the University of California, Los Angeles, and the medical director of endoscopy at the UCLA Health System. He reported relationships with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

References

1. Bartles RL et al. Gastrointest Endosc. 2018 Aug;88(2):306-13.e2.

2. Day LW et al. Gastrointest Endosc. 2021 Jan;93(1):11-33.e6.

3. Bang JY et al. Gut. 2019 Nov;68(11):1915-7.

4. Bomman S et al. Endosc Int Open. 2021 Aug 23;9(9):E1404-12.

Dear colleagues,

Innovation is the livelihood of our field, driving major advances in endoscopy and attracting many of us to Gastroenterology. From the development of endoscopic retrograde cholangiopancreatography to the wide-spread adoption of third space endoscopy, we continue to push the boundaries of our practice. But what is the next big disruption in GI, and how will it impact us? In this issue of Perspectives, two experts present their thoughts on current hot topics in GI. Dr. Jeremy Glissen Brown discusses the application of artificial intelligence in GI highlighting its promise but also raising important questions. Dr. Raman Muthusamy elaborates on single-use endoscopes – are they the wave of the future in preventing infection and meeting patient preference? Or will their long-term cost and environmental impact limit their use? I welcome your own thoughts on disruptive innovation in Gastroenterology – share with us on Twitter @AGA_GIHN and by email at [email protected].

Gyanprakash A. Ketwaroo, MD, MSc, is an associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

The AI revolution, with some important caveats

BY JEREMY R. GLISSEN BROWN, MD, MSC

In 2018, Japan’s Pharmaceutical and Medical Device Agency approved the first artificial intelligence (AI)–based tool, a computer-aided diagnosis system (CADx) for use in clinical practice.¹ Since that time, we have seen regulatory approval for a variety of deep learning and AI-based tools in endoscopy and beyond. In addition, there has been an enormous amount of commercial and research interest in AI-based tools in clinical medicine and gastroenterology, and it is almost impossible to open a major gastroenterology journal or go to an academic conference without encountering a slew of AI-based projects.

Many thought and industry leaders say that we are in the midst of an AI revolution in gastroenterology. Indeed, we are at a period of unprecedented growth for deep learning and AI for several reasons, including a recent shift toward data-driven approaches, advancement of machine-learning techniques, and increased computing power. There is, however, also an unprecedented amount of scrutiny and thoughtful conversation about the role AI might play in clinical practice and how we use and regulate these tools in the clinical setting. We are thus in a unique position to ask ourselves the essential question: “Are we on the cusp of an AI revolution in gastroenterology, or are we seeing the release of medical software that is perhaps at best useful in a niche environment and at worse a hype-driven novelty without much clinical benefit?” We will use the most popular use-case, computer aided detection (CADe) of polyps in the colon, to explore this question. In the end, I believe that deep-learning technology will fundamentally change the way we practice gastroenterology. However, this is the perfect time to explore what this means now, and what we can do to shape what it will mean for the future.

CADe: Promise and questions

CADe is a computer vision task that involves localization, such as finding a polyp during colonoscopy and highlighting it with a hollow box. CADe in colonoscopy is perhaps the most well-studied application of deep learning in GI endoscopy to date and is furthest along in the development-implementation pipeline. Because of this, it is an ideal use-case for examining both the evidence that currently supports its use as well as the questions that have come up as we are starting to see CADe algorithms deployed in clinical practice. It is honestly astounding to think that, just 5 years ago, we were talking about CADe as a research concept. While early efforts applying traditional machine learning date back at least to the 1990s, we started to see prospective studies of CADe systems with undetectable or nearly undetectable latency in 2019.² Since that time we have seen the publication of at least 10 randomized clinical trials involving CADe.

CADe clearly has an impact on some of the conventional quality metrics we use for colonoscopy. While there is considerable heterogeneity in region and design among these trials, most show a significant increase in adenoma detection rate (ADR) and adenomas per colonoscopy. Tandem studies show decreases in adenoma miss rate, and at least one study showed a decrease in sessile serrated lesion miss rate as well. In one of the first randomized, controlled trials across multiple endoscopy centers in Italy, Repici and colleagues showed an increase in ADR from 40.4% in the control group to 54.8% in the CADe group (RR, 1.30; 95% confidence interval, 1.14-1.45).3 Because of pioneering trials such as this one, there are currently several CADe systems that have received regulatory approval in Europe, Asia, and the United States and are being deployed commercially.

It is also clear that the technology is there. In clinical practice, the Food and Drug Administration–approved systems work smoothly, with little to no detectable latency and generally low false-positive and false-negative rates. With clinical deployment, however, we have seen the emergence of healthy debate surrounding every aspect of this task-specific AI. On the development side, important questions include transparency of development data, ensuring that algorithm development is ethical and equitable (as deep learning is susceptible to exacerbating human biases) and methods of data labeling. On the deployment level, important concerns include proper regulation of locked versus “open” algorithms and downstream effects on cost.

In addition, with CADe we have seen a variety of clinical questions crop up because of the novelty of the technology. These include the concern that the increase in ADR we have seen thus far is driven in large part by diminutive and small adenomas (with healthy debate in turn as to these entities’ influence on interval colorectal cancer rates), the effect CADe might have on fellowship training to detect polyps with the human eye, and whether the technology affects sessile serrated lesion detection rates or not. The great thing about such questions is that they have inspired novel research related to CADe in the clinical setting, including how CADe affects trainee ADR, how CADe affects gaze patterns, and how CADe affects recommended surveillance intervals.

CADx, novel applications, and the future

Though there is not space to expand in this particular forum, it is safe to say that with the advancement of CADx in endoscopy and colonoscopy, we have seen similar and novel questions come up. The beautiful thing about all of this is that we are just scratching the surface of what is achievable with deep learning. We have started to see novel projects utilizing deep-learning algorithms, from detecting cirrhosis on ECG to automatically classifying stool consistency on the Bristol Stool Scale from pictures of stool. I ultimately do think that the deployment of AI tools will fundamentally change the way we practice and think about gastroenterology. We are at an incredibly exciting time where we as physicians have the power to shape what that looks like, how we think about AI deployment and regulation and where we go from here.

Dr. Glissen Brown is with the division of gastroenterology and hepatology at Duke University Medical Center, Durham, N.C. He has served as a consultant for Medtronic.

References

1. Aisu N et al. PLOS Digital Health. 2021 Jan 18. doi: 10.1371/journal.pdig.0000001.

2. Wang P et al. Gut. 2019 Oct;68(10):1813-9.

3. Repici A et al. Gastroenterology. 2020 Aug;159(2):512-20.e7.

What’s the future of single-use endoscopes?

BY V. RAMAN MUTHUSAMY, MD, MAS

Single-use endoscopes have been proposed as a definitive solution to the risk of endoscope-transmitted infections. While these infections have been reported for several decades, they have traditionally been associated with identified breaches in the reprocessing protocol. In 2015, numerous cases of duodenoscope-transmitted infections were reported after endoscopic retrograde cholangiopancreatography (ERCP) procedures. Many, if not most, of these cases were not associated with identified deviations from standard high-level disinfection protocols and occurred at high-volume experienced facilities. A subsequent FDA postmarket surveillance study found contamination rates were linked with potentially pathogenic bacteria in approximately 5% of duodenoscopes. Thus, amid growing concerns about the ability to adequately clean these complex devices, these events prompted the development of single-use duodenoscopes. Given the multifactorial causes leading to contaminated duodenoscopes, the advantages of such single-use devices are their ability to ensure the elimination of the potential of infection transmission as these devices are never reused. In addition to this primary benefit, the ability to create single-use devices could lead to more easily available specialty scopes and allow variations in endoscope design that could improve ergonomics. Single-use devices may also expand the ability to provide endoscopic services by eliminating the need for device reprocessing equipment at low-volume sites. However, several concerns have been raised regarding their use, especially if it were to become widespread. These include issues of device quality and performance (potentially leading to more failed cases or adverse events), cost, their environmental impact and current uncertainty regarding their indications for use. Furthermore, new alternatives such as reusable devices with partially disposable components or future low-temperature sterilization options may minimize the need for such devices. We will briefly discuss these issues in more detail below.

Given that nearly all cases of GI device–transmitted infections where standard reprocessing protocols were followed have occurred in duodenoscopes, I will focus on single-use duodenoscopes in this article. It is important that we reassure our patients and colleagues that standard reprocessing appears to be extremely effective with all other types of devices, including elevator containing linear echoendoscopes. Studies investigating the causes of why duodenoscopes have primarily been associated with device-transmitted outbreaks have focused on the complexity of the elevator including its recesses, fixed end-cap and wire channels. However, culturing has shown that up to one-third of contamination may occur in the instrument channels or in the region of the biopsy cap, leading to some potential residual sites of infection even when newly developed reusable devices with disposable elevators/end-caps are utilized.¹ Another challenge with reprocessing is the ability to prove residual contamination does not exist. While culturing the devices after reprocessing is most used, it should be noted many sites with outbreaks failed to culture the culprit bacteria from the devices as accessing the sites of contamination can be challenging. The use of other markers of residual contamination such as ATP and tests for residual blood/protein have yielded variable results. Specifically, ATP testing has not correlated well with culture results but may be helpful in assessing the quality of manual cleaning.²

These challenges have made the concept of single-use devices more appealing given the lack of a need reprocess devices or validate cleaning efficacy. Currently, there are two FDA-approved devices on the market, but the published literature to date has largely involved one of these devices. To date, in four published studies that have assessed the clinical performance of single-use duodenoscopes in over 400 patients, procedural success rates have ranged from 91% to 97% with adverse event rates and endoscopist satisfaction scores comparable to reusable devices. Most of these users were expert biliary endoscopists and more data are needed regarding the performance of the device in lower-volume and nonexpert users. While indications for use in these studies have varied, I feel that there are four potential scenarios to utilize these devices: in patients with known multidrug-resistant organisms undergoing ERCP; to facilitate logistics/operations when a reusable device is not available; in critically ill patients who would not tolerate a scope-acquired infection; and in procedures associated with a risk of bacteremia.

While preliminary data suggest single-use duodenoscopes are safe and effective in expert hands, concerns exist regarding their implementation more broadly into clinical practice. First, the devices cost between $1,500-3,000, making them impractical for many health systems. One study estimated the break-even cost of the device to be $800-1,300 based on variation in site volume and device contamination rates.³ However, it should be noted that current enhanced reprocessing protocols for reusable devices may add an additional $75,000-$400,000 per year based on center volume.⁴ In the United States, there is currently payment by federal and some commercial payors that cover part or all of the device cost, but whether this will continue long-term is unclear. In addition, there is significant concern regarding the environmental impact of a broader mover to single-use devices. Reprocessing programs do exist for these devices, but detailed analyses regarding the environmental effects of a strategy using single-use versus reusable devices and the waste generated from each are needed.

Finally, while primarily created to avoid device-related infection transmission, other benefits can be realized with single-use devices. The potential for ergonomic enhancements (variable handle sizes or shaft stiffness, R- and L-handed scopes) as well as the creation of specialty devices (extra-long or thin devices, devices with special optical or rotational capabilities) may become more feasible with a single-use platform. Finally, the pace of endoscopic innovation and refinement is likely to quicken with a single use platform, and new advancements can be incorporated in a timelier manner.

Conclusion

In summary, I believe single-use devices offer the potential to improve the safety of endoscopic procedures as well as improve procedural access, enhance ergonomics, and foster and expedite device innovation. However, reductions in cost, refining their indications, and developing recycling programs to minimize their environmental impact will be essential before more widespread adoption is achieved.

Dr. Muthusamy is a professor of clinical medicine at the University of California, Los Angeles, and the medical director of endoscopy at the UCLA Health System. He reported relationships with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

References

1. Bartles RL et al. Gastrointest Endosc. 2018 Aug;88(2):306-13.e2.

2. Day LW et al. Gastrointest Endosc. 2021 Jan;93(1):11-33.e6.

3. Bang JY et al. Gut. 2019 Nov;68(11):1915-7.

4. Bomman S et al. Endosc Int Open. 2021 Aug 23;9(9):E1404-12.

Dear colleagues,

Innovation is the livelihood of our field, driving major advances in endoscopy and attracting many of us to Gastroenterology. From the development of endoscopic retrograde cholangiopancreatography to the wide-spread adoption of third space endoscopy, we continue to push the boundaries of our practice. But what is the next big disruption in GI, and how will it impact us? In this issue of Perspectives, two experts present their thoughts on current hot topics in GI. Dr. Jeremy Glissen Brown discusses the application of artificial intelligence in GI highlighting its promise but also raising important questions. Dr. Raman Muthusamy elaborates on single-use endoscopes – are they the wave of the future in preventing infection and meeting patient preference? Or will their long-term cost and environmental impact limit their use? I welcome your own thoughts on disruptive innovation in Gastroenterology – share with us on Twitter @AGA_GIHN and by email at [email protected].

Gyanprakash A. Ketwaroo, MD, MSc, is an associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven (Conn.) VA Medical Center. He is an associate editor for GI & Hepatology News.

The AI revolution, with some important caveats

BY JEREMY R. GLISSEN BROWN, MD, MSC

In 2018, Japan’s Pharmaceutical and Medical Device Agency approved the first artificial intelligence (AI)–based tool, a computer-aided diagnosis system (CADx) for use in clinical practice.¹ Since that time, we have seen regulatory approval for a variety of deep learning and AI-based tools in endoscopy and beyond. In addition, there has been an enormous amount of commercial and research interest in AI-based tools in clinical medicine and gastroenterology, and it is almost impossible to open a major gastroenterology journal or go to an academic conference without encountering a slew of AI-based projects.

Many thought and industry leaders say that we are in the midst of an AI revolution in gastroenterology. Indeed, we are at a period of unprecedented growth for deep learning and AI for several reasons, including a recent shift toward data-driven approaches, advancement of machine-learning techniques, and increased computing power. There is, however, also an unprecedented amount of scrutiny and thoughtful conversation about the role AI might play in clinical practice and how we use and regulate these tools in the clinical setting. We are thus in a unique position to ask ourselves the essential question: “Are we on the cusp of an AI revolution in gastroenterology, or are we seeing the release of medical software that is perhaps at best useful in a niche environment and at worse a hype-driven novelty without much clinical benefit?” We will use the most popular use-case, computer aided detection (CADe) of polyps in the colon, to explore this question. In the end, I believe that deep-learning technology will fundamentally change the way we practice gastroenterology. However, this is the perfect time to explore what this means now, and what we can do to shape what it will mean for the future.

CADe: Promise and questions

CADe is a computer vision task that involves localization, such as finding a polyp during colonoscopy and highlighting it with a hollow box. CADe in colonoscopy is perhaps the most well-studied application of deep learning in GI endoscopy to date and is furthest along in the development-implementation pipeline. Because of this, it is an ideal use-case for examining both the evidence that currently supports its use as well as the questions that have come up as we are starting to see CADe algorithms deployed in clinical practice. It is honestly astounding to think that, just 5 years ago, we were talking about CADe as a research concept. While early efforts applying traditional machine learning date back at least to the 1990s, we started to see prospective studies of CADe systems with undetectable or nearly undetectable latency in 2019.² Since that time we have seen the publication of at least 10 randomized clinical trials involving CADe.

CADe clearly has an impact on some of the conventional quality metrics we use for colonoscopy. While there is considerable heterogeneity in region and design among these trials, most show a significant increase in adenoma detection rate (ADR) and adenomas per colonoscopy. Tandem studies show decreases in adenoma miss rate, and at least one study showed a decrease in sessile serrated lesion miss rate as well. In one of the first randomized, controlled trials across multiple endoscopy centers in Italy, Repici and colleagues showed an increase in ADR from 40.4% in the control group to 54.8% in the CADe group (RR, 1.30; 95% confidence interval, 1.14-1.45).3 Because of pioneering trials such as this one, there are currently several CADe systems that have received regulatory approval in Europe, Asia, and the United States and are being deployed commercially.

It is also clear that the technology is there. In clinical practice, the Food and Drug Administration–approved systems work smoothly, with little to no detectable latency and generally low false-positive and false-negative rates. With clinical deployment, however, we have seen the emergence of healthy debate surrounding every aspect of this task-specific AI. On the development side, important questions include transparency of development data, ensuring that algorithm development is ethical and equitable (as deep learning is susceptible to exacerbating human biases) and methods of data labeling. On the deployment level, important concerns include proper regulation of locked versus “open” algorithms and downstream effects on cost.

In addition, with CADe we have seen a variety of clinical questions crop up because of the novelty of the technology. These include the concern that the increase in ADR we have seen thus far is driven in large part by diminutive and small adenomas (with healthy debate in turn as to these entities’ influence on interval colorectal cancer rates), the effect CADe might have on fellowship training to detect polyps with the human eye, and whether the technology affects sessile serrated lesion detection rates or not. The great thing about such questions is that they have inspired novel research related to CADe in the clinical setting, including how CADe affects trainee ADR, how CADe affects gaze patterns, and how CADe affects recommended surveillance intervals.

CADx, novel applications, and the future

Though there is not space to expand in this particular forum, it is safe to say that with the advancement of CADx in endoscopy and colonoscopy, we have seen similar and novel questions come up. The beautiful thing about all of this is that we are just scratching the surface of what is achievable with deep learning. We have started to see novel projects utilizing deep-learning algorithms, from detecting cirrhosis on ECG to automatically classifying stool consistency on the Bristol Stool Scale from pictures of stool. I ultimately do think that the deployment of AI tools will fundamentally change the way we practice and think about gastroenterology. We are at an incredibly exciting time where we as physicians have the power to shape what that looks like, how we think about AI deployment and regulation and where we go from here.

Dr. Glissen Brown is with the division of gastroenterology and hepatology at Duke University Medical Center, Durham, N.C. He has served as a consultant for Medtronic.

References

1. Aisu N et al. PLOS Digital Health. 2021 Jan 18. doi: 10.1371/journal.pdig.0000001.

2. Wang P et al. Gut. 2019 Oct;68(10):1813-9.

3. Repici A et al. Gastroenterology. 2020 Aug;159(2):512-20.e7.

What’s the future of single-use endoscopes?

BY V. RAMAN MUTHUSAMY, MD, MAS

Single-use endoscopes have been proposed as a definitive solution to the risk of endoscope-transmitted infections. While these infections have been reported for several decades, they have traditionally been associated with identified breaches in the reprocessing protocol. In 2015, numerous cases of duodenoscope-transmitted infections were reported after endoscopic retrograde cholangiopancreatography (ERCP) procedures. Many, if not most, of these cases were not associated with identified deviations from standard high-level disinfection protocols and occurred at high-volume experienced facilities. A subsequent FDA postmarket surveillance study found contamination rates were linked with potentially pathogenic bacteria in approximately 5% of duodenoscopes. Thus, amid growing concerns about the ability to adequately clean these complex devices, these events prompted the development of single-use duodenoscopes. Given the multifactorial causes leading to contaminated duodenoscopes, the advantages of such single-use devices are their ability to ensure the elimination of the potential of infection transmission as these devices are never reused. In addition to this primary benefit, the ability to create single-use devices could lead to more easily available specialty scopes and allow variations in endoscope design that could improve ergonomics. Single-use devices may also expand the ability to provide endoscopic services by eliminating the need for device reprocessing equipment at low-volume sites. However, several concerns have been raised regarding their use, especially if it were to become widespread. These include issues of device quality and performance (potentially leading to more failed cases or adverse events), cost, their environmental impact and current uncertainty regarding their indications for use. Furthermore, new alternatives such as reusable devices with partially disposable components or future low-temperature sterilization options may minimize the need for such devices. We will briefly discuss these issues in more detail below.

Given that nearly all cases of GI device–transmitted infections where standard reprocessing protocols were followed have occurred in duodenoscopes, I will focus on single-use duodenoscopes in this article. It is important that we reassure our patients and colleagues that standard reprocessing appears to be extremely effective with all other types of devices, including elevator containing linear echoendoscopes. Studies investigating the causes of why duodenoscopes have primarily been associated with device-transmitted outbreaks have focused on the complexity of the elevator including its recesses, fixed end-cap and wire channels. However, culturing has shown that up to one-third of contamination may occur in the instrument channels or in the region of the biopsy cap, leading to some potential residual sites of infection even when newly developed reusable devices with disposable elevators/end-caps are utilized.¹ Another challenge with reprocessing is the ability to prove residual contamination does not exist. While culturing the devices after reprocessing is most used, it should be noted many sites with outbreaks failed to culture the culprit bacteria from the devices as accessing the sites of contamination can be challenging. The use of other markers of residual contamination such as ATP and tests for residual blood/protein have yielded variable results. Specifically, ATP testing has not correlated well with culture results but may be helpful in assessing the quality of manual cleaning.²

These challenges have made the concept of single-use devices more appealing given the lack of a need reprocess devices or validate cleaning efficacy. Currently, there are two FDA-approved devices on the market, but the published literature to date has largely involved one of these devices. To date, in four published studies that have assessed the clinical performance of single-use duodenoscopes in over 400 patients, procedural success rates have ranged from 91% to 97% with adverse event rates and endoscopist satisfaction scores comparable to reusable devices. Most of these users were expert biliary endoscopists and more data are needed regarding the performance of the device in lower-volume and nonexpert users. While indications for use in these studies have varied, I feel that there are four potential scenarios to utilize these devices: in patients with known multidrug-resistant organisms undergoing ERCP; to facilitate logistics/operations when a reusable device is not available; in critically ill patients who would not tolerate a scope-acquired infection; and in procedures associated with a risk of bacteremia.

While preliminary data suggest single-use duodenoscopes are safe and effective in expert hands, concerns exist regarding their implementation more broadly into clinical practice. First, the devices cost between $1,500-3,000, making them impractical for many health systems. One study estimated the break-even cost of the device to be $800-1,300 based on variation in site volume and device contamination rates.³ However, it should be noted that current enhanced reprocessing protocols for reusable devices may add an additional $75,000-$400,000 per year based on center volume.⁴ In the United States, there is currently payment by federal and some commercial payors that cover part or all of the device cost, but whether this will continue long-term is unclear. In addition, there is significant concern regarding the environmental impact of a broader mover to single-use devices. Reprocessing programs do exist for these devices, but detailed analyses regarding the environmental effects of a strategy using single-use versus reusable devices and the waste generated from each are needed.

Finally, while primarily created to avoid device-related infection transmission, other benefits can be realized with single-use devices. The potential for ergonomic enhancements (variable handle sizes or shaft stiffness, R- and L-handed scopes) as well as the creation of specialty devices (extra-long or thin devices, devices with special optical or rotational capabilities) may become more feasible with a single-use platform. Finally, the pace of endoscopic innovation and refinement is likely to quicken with a single use platform, and new advancements can be incorporated in a timelier manner.

Conclusion

In summary, I believe single-use devices offer the potential to improve the safety of endoscopic procedures as well as improve procedural access, enhance ergonomics, and foster and expedite device innovation. However, reductions in cost, refining their indications, and developing recycling programs to minimize their environmental impact will be essential before more widespread adoption is achieved.

Dr. Muthusamy is a professor of clinical medicine at the University of California, Los Angeles, and the medical director of endoscopy at the UCLA Health System. He reported relationships with Medtronic, Boston Scientific, Motus GI, Endogastric Solutions, and Capsovision.

References

1. Bartles RL et al. Gastrointest Endosc. 2018 Aug;88(2):306-13.e2.

2. Day LW et al. Gastrointest Endosc. 2021 Jan;93(1):11-33.e6.

3. Bang JY et al. Gut. 2019 Nov;68(11):1915-7.

4. Bomman S et al. Endosc Int Open. 2021 Aug 23;9(9):E1404-12.

In 2007 (coinciding with the inaugural year of GI & Hepatology News), the National Institutes of Health launched the initial phase of the Human Microbiome Project (HMP), marking an important milestone in our study and understanding of the gut microbiome. The HMP, which was supported by “only” approximately $20 million of funding in its first year, served as a catalyst for the development of computational tools, clinical protocols, and reference datasets for an emerging field that now approaches nearly $2 billion per year in market value of diagnostics and therapeutics.

Over the past 15 years, many important discoveries about the microbiome have been made, particularly in the fields of gastroenterology, hepatology, and nutrition. The transplantation of gut microbiome from one person to another has been shown to be more than 90% effective in the treatment of recurrent C. difficile infection, disrupting our current therapeutic algorithms of repetitive antibiotics. Other exciting discoveries have included the relationship between the gut microbiome and enteric nervous system, and its roles in the regulation of metabolism and obesity and in the progression of liver fibrosis and cancer.

ChrisChrisW/Getty Images

Looking ahead, several exciting areas related to digestive health and the microbiome are being prioritized, including the role of probiotics in nutrition, the complex relationship of the bidirectional “gut-brain” axis, and further development of analytics to define and deliver precision medicine across a wide range of digestive disorders. Without a doubt, emerging microbiome discoveries will be prominently featured in the pages of GI & Hepatology News over the coming years to keep our readers informed of these cutting-edge findings.

Dr. Rosenberg is medical director of the North Shore Endoscopy Center and director of clinical research at GI Alliance of Illinois in Gurnee, Ill. Dr. Rosenberg is a consultant for Aimmune Therapeutics and performs clinical research with Ferring Pharmaceuticals.

In 2007 (coinciding with the inaugural year of GI & Hepatology News), the National Institutes of Health launched the initial phase of the Human Microbiome Project (HMP), marking an important milestone in our study and understanding of the gut microbiome. The HMP, which was supported by “only” approximately $20 million of funding in its first year, served as a catalyst for the development of computational tools, clinical protocols, and reference datasets for an emerging field that now approaches nearly $2 billion per year in market value of diagnostics and therapeutics.

Over the past 15 years, many important discoveries about the microbiome have been made, particularly in the fields of gastroenterology, hepatology, and nutrition. The transplantation of gut microbiome from one person to another has been shown to be more than 90% effective in the treatment of recurrent C. difficile infection, disrupting our current therapeutic algorithms of repetitive antibiotics. Other exciting discoveries have included the relationship between the gut microbiome and enteric nervous system, and its roles in the regulation of metabolism and obesity and in the progression of liver fibrosis and cancer.

ChrisChrisW/Getty Images

Looking ahead, several exciting areas related to digestive health and the microbiome are being prioritized, including the role of probiotics in nutrition, the complex relationship of the bidirectional “gut-brain” axis, and further development of analytics to define and deliver precision medicine across a wide range of digestive disorders. Without a doubt, emerging microbiome discoveries will be prominently featured in the pages of GI & Hepatology News over the coming years to keep our readers informed of these cutting-edge findings.

Dr. Rosenberg is medical director of the North Shore Endoscopy Center and director of clinical research at GI Alliance of Illinois in Gurnee, Ill. Dr. Rosenberg is a consultant for Aimmune Therapeutics and performs clinical research with Ferring Pharmaceuticals.

In 2007 (coinciding with the inaugural year of GI & Hepatology News), the National Institutes of Health launched the initial phase of the Human Microbiome Project (HMP), marking an important milestone in our study and understanding of the gut microbiome. The HMP, which was supported by “only” approximately $20 million of funding in its first year, served as a catalyst for the development of computational tools, clinical protocols, and reference datasets for an emerging field that now approaches nearly $2 billion per year in market value of diagnostics and therapeutics.

Over the past 15 years, many important discoveries about the microbiome have been made, particularly in the fields of gastroenterology, hepatology, and nutrition. The transplantation of gut microbiome from one person to another has been shown to be more than 90% effective in the treatment of recurrent C. difficile infection, disrupting our current therapeutic algorithms of repetitive antibiotics. Other exciting discoveries have included the relationship between the gut microbiome and enteric nervous system, and its roles in the regulation of metabolism and obesity and in the progression of liver fibrosis and cancer.

ChrisChrisW/Getty Images

Looking ahead, several exciting areas related to digestive health and the microbiome are being prioritized, including the role of probiotics in nutrition, the complex relationship of the bidirectional “gut-brain” axis, and further development of analytics to define and deliver precision medicine across a wide range of digestive disorders. Without a doubt, emerging microbiome discoveries will be prominently featured in the pages of GI & Hepatology News over the coming years to keep our readers informed of these cutting-edge findings.

Dr. Rosenberg is medical director of the North Shore Endoscopy Center and director of clinical research at GI Alliance of Illinois in Gurnee, Ill. Dr. Rosenberg is a consultant for Aimmune Therapeutics and performs clinical research with Ferring Pharmaceuticals.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

Can you talk about the evolution and treatment of human epidermal growth factor receptor 2 (HER2)-low breast cancer?

Dr. Abdou: Until recently, HER2 status had been defined as a positive or negative result, but this convention has evolved, and now a newly defined population with low levels of HER2 expression has been identified. This HER2-low population accounts for about 55% of all breast cancers. Previously, low HER2 expression levels were considered HER2-negative in clinical practice because HER2-targeted therapies had been considered ineffective in this setting. Patients with HER2-low disease therefore had limited targeted treatment options after progression on their primary therapy.

Now, new studies and clinical trials have opened the door to effective treatments for this cohort of patients. The clinical trial DESTINY-Breast04, which was presented at ASCO 2022, led to the first FDA approval in August 2022 of a targeted therapy option for patients with HER2-low breast cancer subtypes, reclassifying this cohort as a new targetable subset in breast cancer.

DESTINY-Breast04 was the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer, not only patients with HER2-positive disease. The phase 3 study enrolled about 557 patients with hormone receptor (HR)-negative or -positive breast cancer and centrally confirmed HER2-low expression who were previously treated with 1 or 2 prior lines of chemotherapy. Patients were randomized to receive either the antibody–drug conjugate trastuzumab deruxtecan or physician’s choice of standard chemotherapy. The risk of disease progression was about 50% lower and the risk of death was about 36% lower with trastuzumab deruxtecan compared with chemotherapy.¹

These impressive and practice-changing results opened the door to a new treatment option for a substantial group of patients with HER2-low disease and significantly expanded the population of patients who can benefit from HER2-targeted therapy.

What molecular characteristics do you take into consideration to help determine whether patients are eligible for these targeted treatment options?

Dr. Abdou: As we said earlier, HER2 status should no longer be recorded as a binary result of either HER2-positive or HER2-negative. It is important to start routinely testing for the level of HER2 expression in the tumor. Obtaining these levels is done through commonly used immunohistochemical (IHC) assays that allow direct visualization of the HER2 protein. Breast tumors considered to be HER2-low are classified as IHC1+ or as IHC2+ with in situ hybridization or FISH-negative status.

HER2-low breast cancer consists of a heterogeneous group of breast cancers, most of which are HR-positive tumors, whereas about 20% are HR-negative tumors. While these tumors may have distinct molecular profiles leading to clinicopathological and prognostic differences within these groups—HR-positive tumors represent more luminal subtypes and HR-negative tumors tend to be predominantly basal-like subtypes—these distinctions do not necessarily affect patient eligibility for targeted therapy. The benefit of trastuzumab deruxtecan was seen in both subgroups, although the HR-positive population was much more well represented in the DESTINY-Breast04 study.

Other than the HER2 expression status, I also take into consideration the presence of clinical comorbidities, particularly pulmonary comorbidities or prior lung injuries. Trastuzumab deruxtecan can cause a potentially serious type of lung toxicity called interstitial lung disease (ILD). In DESTINY-Breast04, ILD developed in about 12% of patients in the trastuzumab deruxtecan group, with 3 deaths as a result.

Therefore, it’s important for us to carefully select these patients and closely monitor them while they’re on treatment.

What is next in the treatment of HER2-low breast cancer, and what would you like to see in the future?

Dr. Abdou: The exciting new field of HER2-low breast cancer has really opened the door to novel studies and clinical trials, several of which are exploring the role of antibody–drug conjugates in patients with metastatic HER2-low disease and others that are studying early-stage HER2-low breast cancer. In early-stage HER2-low breast cancer, we may potentially see an even greater benefit with these drugs because the disease has not yet developed resistance to therapy. Other studies are examining the role of combination therapy in metastatic breast cancer, such as antibody–drug conjugates in combination with immunotherapy and other targeted agents. I look forward to results from those studies.

Also, importantly, as we start using these therapies more widely, I would like to see more accurate and sensitive ways of assessing the HER2 expression status. The current IHC assay, although widely available, fails to identify many women who have HER2 expression in their tumors. I think more sensitive tests may be able to identify even more women who can benefit from these targeted therapies.

Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants.