Originalarbeit
425
Endoscopic Procedures in Patients under Clopidogrel or Dual Antiplatelet Therapy: A Survey among German Gastroenterologists and Current Guidelines Endoskopische Prozeduren unter Clopidogrel oder dualer Thrombozytenaggregationshemmung: Eine Umfrage unter deutschen Gastroenterologen und die aktuellen Leitlinien Authors
A. Abdel Samie1, L. Theilmann1, J. Labenz2 for the ALGK
Affiliations
1
Department of Gastroenterology, Pforzheim Hospital, Pforzheim, Germany ALGK (Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte), Singen, Germany
Schlüsselwörter
Zusammenfassung
Abstract
"
!
!
Hintergrund: Aufgrund des erhöhten Blutungsrisikos empfehlen die aktuellen Leitlinien die Beendigung einer Clopidogrel-Therapie mind. 7 Tage vor high-risk endoskopischen Prozeduren. Allerdings kann die vorzeitige Beendigung einer Clopidogrel-Therapie aufgrund von Stentthrombosen katastrophale kardiovaskuläre Folgen nach sich ziehen. Ziel dieser Arbeit ist, das aktuelle Vorgehen unter deutschen Gastroenterologen bez. endoskopischer Prozeduren unter Clopidogrel/ dualer Thrombozytenaggregationshemmung zu evaluieren. Methoden: Ein Fragebogen bestehend aus 10 Fragen über endoskopische Prozeduren unter Clopidogrel/dualer Thrombozytenaggregationshemmung wurde an alle 220 Mitglieder der ALGK per E-Mail verschickt. Ergebnisse: 73 (33 %) leitende Gastroenterologen sendeten den ausgefüllten Fragebogen zurück. 35 (48 %) der an unserer Umfrage beteiligten Gastroenterologen leiten große endoskopische Einheiten, die über 4000 endoskopische Prozeduren jährlich erbringen. 62 (85 %) der endoskopischen Einheiten führen endoskopische Biopsien unter Clopidogrel durch, während nur 30 (41 %) Kliniken endoskopische Biopsien unter dualer Thrombozytenaggregationshemmung vornehmen. In 36 (49 %) Kliniken werden endoskopische Polypektomien unter Clopidogrel-Monotherapie vorgenommen, im Gegensatz zu nur 4 (5,5 %) Einheiten, die diese Prozedur unter dualer Thrombozytenaggregationshemmung durchführen. In Notfallsituationen hingegen werden in 60 % aller beteiligten Kliniken endoskopische Sphinkterotomien unter Clopidogrel/dualer Thrombozytenaggregationshemmung durchgeführt. Eine perkutane endoskopische Gastrostomie wird in 32 endoskopischen Einheiten (44 %) unter Clopidogrel-Monotherapie vorgenommen, allerdings nur in 4 (5,5 %) Kliniken unter dualer Thrombozytenaggregationshemmung durchgeführt.
Background: Because of the higher risk of bleeding, guidelines recommend cessation of clopidogrel seven days prior to high-risk endoscopic procedures. However, premature cessation of clopidogrel may lead to catastrophic cardiovascular sequelae due to stent thrombosis. We aimed to assess the current clinical practice among German gastroenterologists regarding endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy. Methods: A 10-item questionnaire on endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy was sent by e-mail to all 220 members of the ALGK. Results: 73 (33 %) chief gastroenterologists returned completed questionnaires, 35 (48 %) of whom conduct high-volume endoscopic units performing more than 4000 procedures per annum. 62 (85 %) endoscopic units perform endoscopic biopsies under clopidogrel alone, while just in 30 (41 %) departments biopsies are carried out under dual antiplatelet therapy. In 36 (49 %) GI-units endoscopic polypectomy under clopidogrel monotherapy is performed, in contrast to only 4 (5.5 %) in the case of combined antiplatelet therapy. However, in emergency situations more than 60 % of all participants do perform endoscopic sphincterotomy in patients under clopidogrel/dual antiplatelet therapy. Percutaneous endoscopic gastrostomy is carried out in 32 endoscopic units (44 %) under clopidogrel monotherapy, but only in 4 (5.5 %) under dual antiplatelet therapy. Conclusion: Current guidelines on endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy are mainly based on expert opinion and therefore, backed by only weak evidence. Our survey shows that in this setting the clinical decision making takes place on an individual basis, as there are no data to support the recommendations of the present guidelines.
● Thrombozytenaggregations● ● ● " " "
hemmung Clopidogrel endoskopischen Prozeduren Fragebogen
Key words
● dual antiplatelet therapy ● clopidogrel ● endoscopic procedures ● questionnaire " " " "
received accepted
3.3.2013 27.9.2013
Bibliography DOI http://dx.doi.org/ 10.1055/s-0033-1355862 Z Gastroenterol 2014; 52: 425–428 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0044-2771
Correspondence Dr. Ahmed Abdel Samie, M. D., FACP, FEBGH, FEFIM Department of Gastroenterology Pforzheim Hospital Kanzlerstr. 2 – 6 75175 Pforzheim Germany Tel.: ++ 49/72 31/9 69 36 56 Fax: ++ 49/72 31/9 69 26 82 [email protected]
Abdel Samie A et al. Endoscopic Procedures in … Z Gastroenterol 2014; 52: 425–428
Downloaded by: University of British Columbia. Copyrighted material.
2
Originalarbeit
Schlussfolgerung: Die aktuellen Leitlinien über endoskopische Prozeduren unter Clopidogrel/dualer Thrombozytenaggregationshemmung basieren überwiegend auf Expertenmeinungen und werden deshalb nur von einer schwachen Evidenz untermauert. Unsere Umfrage zeigt, dass in diesem Setting die klinische Entscheidung auf individueller Basis getroffen wird, da es keine Daten gibt, die die aktuellen Leitlinienempfehlungen unterstützen.
Introduction !
Guidelines of the British Society of Gastroenterology [1], the American Society of Gastrointestinal Endoscopy [2], and the European Society of Gastrointestinal Endoscopy [3] recommend cessation of clopidogrel seven days prior to high-risk endoscopic procedures. However, dual antiplatelet therapy has to be used for up to one year after placement of coronary stents. Premature discontinuation of antiplatelet medication during this period is associated with an increased risk for stent thrombosis with severe or even fatal consequences [4]. Moreover, recent data suggest that even after one year of antiplatelet therapy, clopidogrel cessation may result in rebound platelet hyperactivity contributing to increased thromboembolic complications in this setting [5]. Hence, some patients have to undergo endoscopic procedures while still on dual antiplatelet therapy. The aim of this study is to assess how German gastroenterologists handle this common clinical scenario.
Methods !
All 220 members of the ALGK (Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte: Association of Senior Hospital Gastroenterologists) were invited to participate in a 10item questionnaire. The questions addressed different clinical scenarios regarding endoscopic procedures under clopidogrel/ dual antiplatelet therapy. Additionally, data in respect of institutional standard operating procedures (SOPs) on this issue, and the number of endoscopic procedures performed per annum were collected. The questionnaire was sent via e-mail in October 2012.
Statistical analysis All data were collected and analysed with the help of Microsoft Excel for Windows.
Results !
73 (33 %) chief gastroenterologists returned completed questionnaires. In 35 (48 %) departments more than 4000 endoscopic procedures were performed annually. 35 endoscopic units carried out between 2000 and 4000 procedures, and only three units performed less than 2000 endoscopies yearly. SOPs on endoscopic procedures in patients under clopidogrel or dual antiplatelet therapy were established in 32 (44 %) endoscopic units. Endoscopic biopsies are performed in 62 (85 %) endoscopic units under clopidogrel alone, while only in 30 (41 %) departments biopsies are carried out under dual antiplatelet therapy. Endoscopic polypectomy is performed by nearly half of the participating gastroenterologists (49 %) in patients under clopidogrel
Abdel Samie A et al. Endoscopic Procedures in … Z Gastroenterol 2014; 52: 425–428
monotherapy, compared to only four participants (5.5 %) in case of combined antiplatelet therapy. Endoscopic sphincterotomy (ES) is carried out by 17 (23 %) of 73 chief gastroenterologists under clopidogrel, while 10 (14 %) do not perform ES in these patients, and 46 (63 %) do, however, only in emergency situations. If patients are under dual antiplatelet therapy only two respondents (3 %) carry out ES, 27 (36 %) do not, and 44 (60 %) do in emergency situations. Percutaneous endoscopic gastrostomy (PEG) is performed in patients on clopidogrel monotherapy by 32 (44 %) participants, while only four respondents (5.5 %) carry out this procedure in patients under combined antiplatelet therapy. The results of the " Table 1. survey are summarised in ●
Discussion !
Coronary stenting has become an established treatment of ischemic heart disease. Current guidelines [6] recommend the use of dual antiplatelet therapy for at least one month after placement of bare metal stents and at least one year after placement of drug eluting stents. Discontinuation of antiplatelet therapy was the most powerful predictor of drug eluting stent thrombosis in a prospective study including 3021 patients [7]. Hence patients at risk for thromboembolic events should continue this medication during elective high-risk endoscopic procedures. However, given the potentially increased bleeding risk, patients taking acetylsalicylic acid (ASA) for prophylactic purposes should discontinue this medication prior to elective high-risk procedures. Data regarding the management of patients on clopidogrel/combined antiplatelet therapy undergoing endoscopic procedures are limited and current guidelines dealing with this common clinical scenario are mainly based on expert opinion.
Low-risk endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy The incidence of bleeding following gastrointestinal endoscopy varies depending on the procedure. Endoscopic biopsy is considered to be a low-risk procedure. According to the current guide-
Table 1 Feasibility of endoscopic procedures under clopidogrel and dual antiplatelet therapy according to the survey among German senior gastroenterologists
endoscopic procedure
clopidogrel
dual antiplatelet
biopsy
62/73 (85 %)
30/73 (41 %)
therapy polypectomy
36/73 (49 %)
4/73 (5.5 %)
sphincterotomy
17/73 (23 %)
2/73 (3 %)
sphincterotomy in emergency cases
46/73 (63 %)
44/73 (60 %)
percutaneous endoscopic gastrostomy 32/73 (44 %)
4/73 (5.5 %)
Downloaded by: University of British Columbia. Copyrighted material.
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lines in patients on clopidogrel/dual antiplatelet therapy undergoing low-risk endoscopic procedures, the dual therapy can be continued [1 – 3]. In a prospective, single blind, randomised trial including 45 healthy adult volunteers 350 gastroduodenal biopsies were performed under clopidogrel. In this recently published study no significant bleeding occurred in the clopidogrel group [8]. The study from Whitson et al. is the first prospective study on this issue in the gastroenterological literature. Nevertheless, the study included healthy volunteers. In “real life”, patients on clopidogrel/ dual antiplatelet therapy often exhibit relevant comorbidities and require comedication, which may influence not only the efficacy of the antiplatelet therapy but also the bleeding risk. In our survey 59 % of participating gastroenterologists would not perform endoscopic biopsies under dual antiplatelet therapy, while 85 % would do in case of clopidogrel monotherapy, which is in accordance with the current guidelines. Nevertheless, guidelines recommend performing the procedure under uninterrupted antiplatelet therapy, notwithstanding that clopidogrel is given alone or in combination with acetylsalicylic acid (ASA).
High-risk endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy High-risk procedures which may be associated with increased incidence of bleeding include polypectomy, endoscopic sphincterotomy (ES), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), dilation of strictures, percutaneous endoscopic gastrostomy (PEG), and endosonography guided fine-needle aspiration (EUS-FNA) [1 – 3]. According to the current guidelines in patients on dual antiplatelet therapy clopidogrel should be stopped seven days prior to high-risk procedures, while aspirin can be continued [1 – 3]. However, before stopping clopidogrel in high-risk conditions, such as recently implanted drug eluting stents, consultation with the patient’s cardiologist is mandatory. As a general principle, the risk of thromboembolism needs to be balanced against the risk of bleeding during an endoscopic interventional procedure. To date, no prospective data exist in respect of the bleeding risk in patients under clopidogrel/dual antiplatelet therapy undergoing high-risk gastrointestinal endoscopic procedures.
Endoscopic polypectomy in patients under clopidogrel/ dual antiplatelet therapy So far, three retrospective studies were published on the risk of bleeding in patients undergoing colonoscopy with polypectomy under clopidogrel/dual antiplatelet therapy [9 – 11]. The primary outcome of interest in the study from Feagins et al. was delayed post-polypectomy bleeding (PPB), which was defined as bleeding per rectum occurring within 30 days following polypectomy and requiring hospitalsation or treatment. 360 polypectomies were performed in 118 patients under clopidogrel/dual antiplatelet therapy (25/93). Delayed PPB occurred in one patient, who required hospitalisation for two days and endoscopic intervention (clip). Blood transfusion was not necessary in this patient, who was under antiplatelet therapy (ASA 325 mg). In this study, six PPB were documented in the control group (0.32 %). Using the whole sample of 1 967 patients, logistic regression analysis indicated no significant difference between both groups.
The authors concluded that the thrombotic risk of discontinuing clopidogrel prior to colonoscopy may exceed the risk of postpolypectomy bleeding [9]. In another retrospective case-control study, including 142 patients on clopidogrel (375 polypectomies) and 1243 controls (3226 polypectomies) the risk of PPB was significantly higher in patients undergoing the procedure while on clopidogrel and concomitant aspirin/non-steroidal anti-inflammatory drugs. However, clopidogrel alone was not an independent risk factor for PPB, and the authors concluded that routine cessation of clopidogrel prior to colonoscopy/polypectomy is not necessary [10]. In the third small retrospective study on this issue [11], 125 polypectomies were performed in 60 patients under clopidogrel/dual antiplatelet therapy (50/10). Four patients experienced PPB (three immediate and one delayed). However, none of these patients required transfusion of packed red blood cells or re-hospitalisation. The average size of removed polyps was 5.4 mm (3 – 12 mm). This is comparable to the size of polyps removed in the former two studies, so that the safety of removing larger polyps without stopping clopidogrel remains unsettled. Furthermore, in this study prophylactic clip application was performed in all patients, and most of the polyps were removed using the cold snare technique (73 %). The authors hypothesised that, although unproven, both techniques may have contributed to the low bleeding rate in this study [11]. In our survey, the vast majority (95 %) of respondents would not perform endoscopic polypectomy under dual antiplatelet therapy, while about half of the participating gastroenterologists would perform this procedure under clopidogrel monotherapy. This practice is not in accordance with the current guidelines, which all recommend stopping clopidogrel seven days prior to high-risk endoscopic procedures, regardless of whether combined with ASA or not, although as shown above, these recommendations are not supported vigorously by evidence. The risk of gastrointestinal bleeding may increase by 2 – 3-fold in patients on aspirin and clopidogrel compared with aspirin alone as shown in randomised trials [12], and it seems reasonable to assume that combining two antiplatelet agents might increase the risk of bleeding after invasive endoscopic procedures like polypectomy compared with mono therapy. This may explain why in clinical practice most endoscopists would perform high-risk endoscopic procedures under clopidogrel monotherapy, while the vast majority would not in case of combined antiplatelet medication.
Endoscopic sphincterotomy in patients under clopidogrel/dual antiplatelet therapy: So far, there is only one published study on the risk of hemorrhage with clopidogrel/dual antiplatelet usage in patients undergoing ES. In this retrospective study conducted by the authors of this paper emergency ES was performed safely in eight consecutive patients on uninterrupted combined antiplatelet therapy. Neither endoscopically relevant immediate nor clinically significant delayed bleeding was observed [13]. In our survey more than 60 % of the participants would perform endoscopic sphincterotomy under clopidogrel/dual antiplatelet therapy in emergency situations, which is also in accordance with our results but, nevertheless, not supported by the current guidelines.
Abdel Samie A et al. Endoscopic Procedures in … Z Gastroenterol 2014; 52: 425–428
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Originalarbeit
Percutaneous endoscopic gastrostomy in patients under clopidogrel/dual antiplatelet therapy In a retrospective cohort study from Richter et al., 27 procedures were performed in patients under clopidogrel. No bleeding related to the procedure occurred in the first 48 hours following PEG placement [14]. Although current guidelines recommend cessation of clopidogrel seven days prior to PEG placement, 32 (44 %) of participants in this survey would perform percutaneous endoscopic gastrostomy under clopidogrel monotherapy in contrast to only 4 (5.5 %) in cases of dual antiplatelet therapy. In summary, up to now data published on the bleeding risk of gastrointestinal endoscopic procedures in patients under clopidogrel/antiplatelet therapy are scarce and of poor quality. Although the available studies do not prove that clopidogrel/ dual antiplatelet therapy increases the bleeding risk in high-risk endoscopic procedures, they are too limited to assert the opposite, but still, guidelines published so far are not backed by sufficient evidence. Current guidelines recommend stopping clopidogrel for at least one week prior to high-risk endoscopic procedures, as anecdotal experience, and experience from other invasive procedures, such as transbronchial biopsies [15] suggests an increased bleeding risk for interventional endoscopy. Nevertheless, cessation of antiplatelet therapy in such subjects with a high thromboembolic risk may lead to clinical consequences much more severe than the supposed, yet unproved increased rate of bleeding complications. Available data, personal experience, and the results observed in the participating units in this survey with impressive numbers of endoscopic procedures performed annually do not support strict adherence to the present guidelines, but rather clinical decision making on an individual basis. However, a more liberal handling of antiplatelet therapy in patients undergoing elective endoscopic procedures may be associated with increased gastrointestinal risks. Therefore, a future register recording complications of endoscopic procedures under antiplatelet therapy would be helpful.
Acknowledgments !
We would to thank all members of the ALKG for participating in our survey
Abdel Samie A et al. Endoscopic Procedures in … Z Gastroenterol 2014; 52: 425–428
References 01 Veitch AM, Baglin TP, Gershlick AH et al. Guidelines for the management of anticoagulant and antiplatelet therapy in patients undergoing endoscopic procedures. Gut 2008; 57: 1322 – 1329 02 Anderson MA, Ben-Menachem T, Gan SI et al. Management of antithrombotic agents for endoscopic procedures. ASGE Standards of Practice Committee. Gastrointestinal Endoscopy 2009; 70: 1060 – 1070 03 Boustière C, Veitch A, Vanbiervliet G et al. Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2011; 43: 445 – 461 04 Spertus JA, Kettelkamp R, Vance C et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER Registry. Circulation 2006; 113: 2803 – 2809 05 Diehl P, Halscheid C, Olivier C et al. Discontinuation of long term clopidogrel therapy induces platelet rebound hyperaggregability between 2 and 6 weeks post cessation. Clinical Research in Cardiology 2011; 100: 765 – 771 06 King SB, Smith SC, Hirshfeld JW et al. 2007 focused update of the ACC/ AHA/SCAI 2005 guideline update for percutaneous coronary intervention: A report of the American college of cardiology/American heart association task force on practice guidelines: 2007 writing group review new evidence and update the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention, writing on behalf of the 2005 writing committee. Circulation 2008; 117: 261 – 295 07 Airoldi F, Colombo A, Morici N et al. Incidence and predictors of drugeluting stent thrombosis during and after discontinuation of thienopyridines treatment. Circulation 2007; 116: 745 – 754 08 Whitson MJ, Dikman AE, von Althann C et al. Is gastroduodenal biopsy safe in patients receiving aspirin and clopidogrel?: a prospective, randomized study involving 630 biopsies. J Clin Gastroenterol 2011; 45: 228 – 233 09 Feagins LA, Uddin FS, Davila RE et al. The rate of post-polypectomy bleeding for patients on uninterrupted clopidogrel therapy during elective colonoscopy is acceptably low. Digestive Diseases and Sciences 2011; 56: 2631 – 2638 10 Singh M, Mehta N, Murthy UK et al. Postpolypectomy bleeding in patients undergoing colonoscopy on uninterrupted clopidogrel therapy. Gastrointestinal Endoscopy 2010; 71: 998 – 1005 11 Friedland S, Leung CW, Soetikno RM. Colonoscopy with polypectomy in patients taking clopidogrel. Gastroenterology Research 2009; 2: 209 – 212 12 Abraham NS, Hatky MA, Antman EM et al. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: A focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Am J Gastroenterol 2010; 105: 2533 – 2549 13 Abdel SamieA, Sun R, Theilmann L et al. Safety of endoscopic sphincterotomy in patients under dual antiplatelet therapy. Hepatogastroenterology 2012; 60: 124 Epub ahead of print 14 Richter JA, Patrie JT, Richter RP et al. Bleeding after percutaneous endoscopic gastrostomy is linked to serotonin reuptake inhibitors, not aspirin or clopidogrel. Gastrointestinal Endoscopy 2011; 74: 22 – 34 15 Ernst A, Eberhardt R, Wahidi M et al. Effect of routine clopidogrel use on bleeding complications after transbronchial biopsy in humans. Chest 2006; 129: 734 – 737
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425
Endoscopic Procedures in Patients under Clopidogrel or Dual Antiplatelet Therapy: A Survey among German Gastroenterologists and Current Guidelines Endoskopische Prozeduren unter Clopidogrel oder dualer Thrombozytenaggregationshemmung: Eine Umfrage unter deutschen Gastroenterologen und die aktuellen Leitlinien Authors
A. Abdel Samie1, L. Theilmann1, J. Labenz2 for the ALGK
Affiliations
1
Department of Gastroenterology, Pforzheim Hospital, Pforzheim, Germany ALGK (Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte), Singen, Germany
Schlüsselwörter
Zusammenfassung
Abstract
"
!
!
Hintergrund: Aufgrund des erhöhten Blutungsrisikos empfehlen die aktuellen Leitlinien die Beendigung einer Clopidogrel-Therapie mind. 7 Tage vor high-risk endoskopischen Prozeduren. Allerdings kann die vorzeitige Beendigung einer Clopidogrel-Therapie aufgrund von Stentthrombosen katastrophale kardiovaskuläre Folgen nach sich ziehen. Ziel dieser Arbeit ist, das aktuelle Vorgehen unter deutschen Gastroenterologen bez. endoskopischer Prozeduren unter Clopidogrel/ dualer Thrombozytenaggregationshemmung zu evaluieren. Methoden: Ein Fragebogen bestehend aus 10 Fragen über endoskopische Prozeduren unter Clopidogrel/dualer Thrombozytenaggregationshemmung wurde an alle 220 Mitglieder der ALGK per E-Mail verschickt. Ergebnisse: 73 (33 %) leitende Gastroenterologen sendeten den ausgefüllten Fragebogen zurück. 35 (48 %) der an unserer Umfrage beteiligten Gastroenterologen leiten große endoskopische Einheiten, die über 4000 endoskopische Prozeduren jährlich erbringen. 62 (85 %) der endoskopischen Einheiten führen endoskopische Biopsien unter Clopidogrel durch, während nur 30 (41 %) Kliniken endoskopische Biopsien unter dualer Thrombozytenaggregationshemmung vornehmen. In 36 (49 %) Kliniken werden endoskopische Polypektomien unter Clopidogrel-Monotherapie vorgenommen, im Gegensatz zu nur 4 (5,5 %) Einheiten, die diese Prozedur unter dualer Thrombozytenaggregationshemmung durchführen. In Notfallsituationen hingegen werden in 60 % aller beteiligten Kliniken endoskopische Sphinkterotomien unter Clopidogrel/dualer Thrombozytenaggregationshemmung durchgeführt. Eine perkutane endoskopische Gastrostomie wird in 32 endoskopischen Einheiten (44 %) unter Clopidogrel-Monotherapie vorgenommen, allerdings nur in 4 (5,5 %) Kliniken unter dualer Thrombozytenaggregationshemmung durchgeführt.
Background: Because of the higher risk of bleeding, guidelines recommend cessation of clopidogrel seven days prior to high-risk endoscopic procedures. However, premature cessation of clopidogrel may lead to catastrophic cardiovascular sequelae due to stent thrombosis. We aimed to assess the current clinical practice among German gastroenterologists regarding endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy. Methods: A 10-item questionnaire on endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy was sent by e-mail to all 220 members of the ALGK. Results: 73 (33 %) chief gastroenterologists returned completed questionnaires, 35 (48 %) of whom conduct high-volume endoscopic units performing more than 4000 procedures per annum. 62 (85 %) endoscopic units perform endoscopic biopsies under clopidogrel alone, while just in 30 (41 %) departments biopsies are carried out under dual antiplatelet therapy. In 36 (49 %) GI-units endoscopic polypectomy under clopidogrel monotherapy is performed, in contrast to only 4 (5.5 %) in the case of combined antiplatelet therapy. However, in emergency situations more than 60 % of all participants do perform endoscopic sphincterotomy in patients under clopidogrel/dual antiplatelet therapy. Percutaneous endoscopic gastrostomy is carried out in 32 endoscopic units (44 %) under clopidogrel monotherapy, but only in 4 (5.5 %) under dual antiplatelet therapy. Conclusion: Current guidelines on endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy are mainly based on expert opinion and therefore, backed by only weak evidence. Our survey shows that in this setting the clinical decision making takes place on an individual basis, as there are no data to support the recommendations of the present guidelines.
● Thrombozytenaggregations● ● ● " " "
hemmung Clopidogrel endoskopischen Prozeduren Fragebogen
Key words
● dual antiplatelet therapy ● clopidogrel ● endoscopic procedures ● questionnaire " " " "
received accepted
3.3.2013 27.9.2013
Bibliography DOI http://dx.doi.org/ 10.1055/s-0033-1355862 Z Gastroenterol 2014; 52: 425–428 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0044-2771
Correspondence Dr. Ahmed Abdel Samie, M. D., FACP, FEBGH, FEFIM Department of Gastroenterology Pforzheim Hospital Kanzlerstr. 2 – 6 75175 Pforzheim Germany Tel.: ++ 49/72 31/9 69 36 56 Fax: ++ 49/72 31/9 69 26 82 [email protected]
Abdel Samie A et al. Endoscopic Procedures in … Z Gastroenterol 2014; 52: 425–428
Downloaded by: University of British Columbia. Copyrighted material.
2
Originalarbeit
Schlussfolgerung: Die aktuellen Leitlinien über endoskopische Prozeduren unter Clopidogrel/dualer Thrombozytenaggregationshemmung basieren überwiegend auf Expertenmeinungen und werden deshalb nur von einer schwachen Evidenz untermauert. Unsere Umfrage zeigt, dass in diesem Setting die klinische Entscheidung auf individueller Basis getroffen wird, da es keine Daten gibt, die die aktuellen Leitlinienempfehlungen unterstützen.
Introduction !
Guidelines of the British Society of Gastroenterology [1], the American Society of Gastrointestinal Endoscopy [2], and the European Society of Gastrointestinal Endoscopy [3] recommend cessation of clopidogrel seven days prior to high-risk endoscopic procedures. However, dual antiplatelet therapy has to be used for up to one year after placement of coronary stents. Premature discontinuation of antiplatelet medication during this period is associated with an increased risk for stent thrombosis with severe or even fatal consequences [4]. Moreover, recent data suggest that even after one year of antiplatelet therapy, clopidogrel cessation may result in rebound platelet hyperactivity contributing to increased thromboembolic complications in this setting [5]. Hence, some patients have to undergo endoscopic procedures while still on dual antiplatelet therapy. The aim of this study is to assess how German gastroenterologists handle this common clinical scenario.
Methods !
All 220 members of the ALGK (Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte: Association of Senior Hospital Gastroenterologists) were invited to participate in a 10item questionnaire. The questions addressed different clinical scenarios regarding endoscopic procedures under clopidogrel/ dual antiplatelet therapy. Additionally, data in respect of institutional standard operating procedures (SOPs) on this issue, and the number of endoscopic procedures performed per annum were collected. The questionnaire was sent via e-mail in October 2012.
Statistical analysis All data were collected and analysed with the help of Microsoft Excel for Windows.
Results !
73 (33 %) chief gastroenterologists returned completed questionnaires. In 35 (48 %) departments more than 4000 endoscopic procedures were performed annually. 35 endoscopic units carried out between 2000 and 4000 procedures, and only three units performed less than 2000 endoscopies yearly. SOPs on endoscopic procedures in patients under clopidogrel or dual antiplatelet therapy were established in 32 (44 %) endoscopic units. Endoscopic biopsies are performed in 62 (85 %) endoscopic units under clopidogrel alone, while only in 30 (41 %) departments biopsies are carried out under dual antiplatelet therapy. Endoscopic polypectomy is performed by nearly half of the participating gastroenterologists (49 %) in patients under clopidogrel
Abdel Samie A et al. Endoscopic Procedures in … Z Gastroenterol 2014; 52: 425–428
monotherapy, compared to only four participants (5.5 %) in case of combined antiplatelet therapy. Endoscopic sphincterotomy (ES) is carried out by 17 (23 %) of 73 chief gastroenterologists under clopidogrel, while 10 (14 %) do not perform ES in these patients, and 46 (63 %) do, however, only in emergency situations. If patients are under dual antiplatelet therapy only two respondents (3 %) carry out ES, 27 (36 %) do not, and 44 (60 %) do in emergency situations. Percutaneous endoscopic gastrostomy (PEG) is performed in patients on clopidogrel monotherapy by 32 (44 %) participants, while only four respondents (5.5 %) carry out this procedure in patients under combined antiplatelet therapy. The results of the " Table 1. survey are summarised in ●
Discussion !
Coronary stenting has become an established treatment of ischemic heart disease. Current guidelines [6] recommend the use of dual antiplatelet therapy for at least one month after placement of bare metal stents and at least one year after placement of drug eluting stents. Discontinuation of antiplatelet therapy was the most powerful predictor of drug eluting stent thrombosis in a prospective study including 3021 patients [7]. Hence patients at risk for thromboembolic events should continue this medication during elective high-risk endoscopic procedures. However, given the potentially increased bleeding risk, patients taking acetylsalicylic acid (ASA) for prophylactic purposes should discontinue this medication prior to elective high-risk procedures. Data regarding the management of patients on clopidogrel/combined antiplatelet therapy undergoing endoscopic procedures are limited and current guidelines dealing with this common clinical scenario are mainly based on expert opinion.
Low-risk endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy The incidence of bleeding following gastrointestinal endoscopy varies depending on the procedure. Endoscopic biopsy is considered to be a low-risk procedure. According to the current guide-
Table 1 Feasibility of endoscopic procedures under clopidogrel and dual antiplatelet therapy according to the survey among German senior gastroenterologists
endoscopic procedure
clopidogrel
dual antiplatelet
biopsy
62/73 (85 %)
30/73 (41 %)
therapy polypectomy
36/73 (49 %)
4/73 (5.5 %)
sphincterotomy
17/73 (23 %)
2/73 (3 %)
sphincterotomy in emergency cases
46/73 (63 %)
44/73 (60 %)
percutaneous endoscopic gastrostomy 32/73 (44 %)
4/73 (5.5 %)
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lines in patients on clopidogrel/dual antiplatelet therapy undergoing low-risk endoscopic procedures, the dual therapy can be continued [1 – 3]. In a prospective, single blind, randomised trial including 45 healthy adult volunteers 350 gastroduodenal biopsies were performed under clopidogrel. In this recently published study no significant bleeding occurred in the clopidogrel group [8]. The study from Whitson et al. is the first prospective study on this issue in the gastroenterological literature. Nevertheless, the study included healthy volunteers. In “real life”, patients on clopidogrel/ dual antiplatelet therapy often exhibit relevant comorbidities and require comedication, which may influence not only the efficacy of the antiplatelet therapy but also the bleeding risk. In our survey 59 % of participating gastroenterologists would not perform endoscopic biopsies under dual antiplatelet therapy, while 85 % would do in case of clopidogrel monotherapy, which is in accordance with the current guidelines. Nevertheless, guidelines recommend performing the procedure under uninterrupted antiplatelet therapy, notwithstanding that clopidogrel is given alone or in combination with acetylsalicylic acid (ASA).
High-risk endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy High-risk procedures which may be associated with increased incidence of bleeding include polypectomy, endoscopic sphincterotomy (ES), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), dilation of strictures, percutaneous endoscopic gastrostomy (PEG), and endosonography guided fine-needle aspiration (EUS-FNA) [1 – 3]. According to the current guidelines in patients on dual antiplatelet therapy clopidogrel should be stopped seven days prior to high-risk procedures, while aspirin can be continued [1 – 3]. However, before stopping clopidogrel in high-risk conditions, such as recently implanted drug eluting stents, consultation with the patient’s cardiologist is mandatory. As a general principle, the risk of thromboembolism needs to be balanced against the risk of bleeding during an endoscopic interventional procedure. To date, no prospective data exist in respect of the bleeding risk in patients under clopidogrel/dual antiplatelet therapy undergoing high-risk gastrointestinal endoscopic procedures.
Endoscopic polypectomy in patients under clopidogrel/ dual antiplatelet therapy So far, three retrospective studies were published on the risk of bleeding in patients undergoing colonoscopy with polypectomy under clopidogrel/dual antiplatelet therapy [9 – 11]. The primary outcome of interest in the study from Feagins et al. was delayed post-polypectomy bleeding (PPB), which was defined as bleeding per rectum occurring within 30 days following polypectomy and requiring hospitalsation or treatment. 360 polypectomies were performed in 118 patients under clopidogrel/dual antiplatelet therapy (25/93). Delayed PPB occurred in one patient, who required hospitalisation for two days and endoscopic intervention (clip). Blood transfusion was not necessary in this patient, who was under antiplatelet therapy (ASA 325 mg). In this study, six PPB were documented in the control group (0.32 %). Using the whole sample of 1 967 patients, logistic regression analysis indicated no significant difference between both groups.
The authors concluded that the thrombotic risk of discontinuing clopidogrel prior to colonoscopy may exceed the risk of postpolypectomy bleeding [9]. In another retrospective case-control study, including 142 patients on clopidogrel (375 polypectomies) and 1243 controls (3226 polypectomies) the risk of PPB was significantly higher in patients undergoing the procedure while on clopidogrel and concomitant aspirin/non-steroidal anti-inflammatory drugs. However, clopidogrel alone was not an independent risk factor for PPB, and the authors concluded that routine cessation of clopidogrel prior to colonoscopy/polypectomy is not necessary [10]. In the third small retrospective study on this issue [11], 125 polypectomies were performed in 60 patients under clopidogrel/dual antiplatelet therapy (50/10). Four patients experienced PPB (three immediate and one delayed). However, none of these patients required transfusion of packed red blood cells or re-hospitalisation. The average size of removed polyps was 5.4 mm (3 – 12 mm). This is comparable to the size of polyps removed in the former two studies, so that the safety of removing larger polyps without stopping clopidogrel remains unsettled. Furthermore, in this study prophylactic clip application was performed in all patients, and most of the polyps were removed using the cold snare technique (73 %). The authors hypothesised that, although unproven, both techniques may have contributed to the low bleeding rate in this study [11]. In our survey, the vast majority (95 %) of respondents would not perform endoscopic polypectomy under dual antiplatelet therapy, while about half of the participating gastroenterologists would perform this procedure under clopidogrel monotherapy. This practice is not in accordance with the current guidelines, which all recommend stopping clopidogrel seven days prior to high-risk endoscopic procedures, regardless of whether combined with ASA or not, although as shown above, these recommendations are not supported vigorously by evidence. The risk of gastrointestinal bleeding may increase by 2 – 3-fold in patients on aspirin and clopidogrel compared with aspirin alone as shown in randomised trials [12], and it seems reasonable to assume that combining two antiplatelet agents might increase the risk of bleeding after invasive endoscopic procedures like polypectomy compared with mono therapy. This may explain why in clinical practice most endoscopists would perform high-risk endoscopic procedures under clopidogrel monotherapy, while the vast majority would not in case of combined antiplatelet medication.
Endoscopic sphincterotomy in patients under clopidogrel/dual antiplatelet therapy: So far, there is only one published study on the risk of hemorrhage with clopidogrel/dual antiplatelet usage in patients undergoing ES. In this retrospective study conducted by the authors of this paper emergency ES was performed safely in eight consecutive patients on uninterrupted combined antiplatelet therapy. Neither endoscopically relevant immediate nor clinically significant delayed bleeding was observed [13]. In our survey more than 60 % of the participants would perform endoscopic sphincterotomy under clopidogrel/dual antiplatelet therapy in emergency situations, which is also in accordance with our results but, nevertheless, not supported by the current guidelines.
Abdel Samie A et al. Endoscopic Procedures in … Z Gastroenterol 2014; 52: 425–428
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Percutaneous endoscopic gastrostomy in patients under clopidogrel/dual antiplatelet therapy In a retrospective cohort study from Richter et al., 27 procedures were performed in patients under clopidogrel. No bleeding related to the procedure occurred in the first 48 hours following PEG placement [14]. Although current guidelines recommend cessation of clopidogrel seven days prior to PEG placement, 32 (44 %) of participants in this survey would perform percutaneous endoscopic gastrostomy under clopidogrel monotherapy in contrast to only 4 (5.5 %) in cases of dual antiplatelet therapy. In summary, up to now data published on the bleeding risk of gastrointestinal endoscopic procedures in patients under clopidogrel/antiplatelet therapy are scarce and of poor quality. Although the available studies do not prove that clopidogrel/ dual antiplatelet therapy increases the bleeding risk in high-risk endoscopic procedures, they are too limited to assert the opposite, but still, guidelines published so far are not backed by sufficient evidence. Current guidelines recommend stopping clopidogrel for at least one week prior to high-risk endoscopic procedures, as anecdotal experience, and experience from other invasive procedures, such as transbronchial biopsies [15] suggests an increased bleeding risk for interventional endoscopy. Nevertheless, cessation of antiplatelet therapy in such subjects with a high thromboembolic risk may lead to clinical consequences much more severe than the supposed, yet unproved increased rate of bleeding complications. Available data, personal experience, and the results observed in the participating units in this survey with impressive numbers of endoscopic procedures performed annually do not support strict adherence to the present guidelines, but rather clinical decision making on an individual basis. However, a more liberal handling of antiplatelet therapy in patients undergoing elective endoscopic procedures may be associated with increased gastrointestinal risks. Therefore, a future register recording complications of endoscopic procedures under antiplatelet therapy would be helpful.
Acknowledgments !
We would to thank all members of the ALKG for participating in our survey
Abdel Samie A et al. Endoscopic Procedures in … Z Gastroenterol 2014; 52: 425–428
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