Post-polypectomy Bleeding in Patients on Clopidogrel
Post-polypectomy Bleeding in Patients on Clopidogrel
Our search strategy yielded 151 studies, of which 127 were excluded on review of the title and abstract. A further 19 studies were excluded after careful review of the full text. Where only partial information on the outcomes of interest was reported in the article, the authors were contacted and asked to provide additional information. Using a questionnaire, Waters et al. assessed the risk of cardiovascular events and PPB in patients who continued/discontinued clopidogrel prior to polypectomy. The authors could not provide specific results for inclusion in our meta-analysis. Two abstracts were excluded by Feagins and colleagues, as the subjects were part of larger data sets of studies included in this meta-analysis.
Overall, five studies were eligible for inclusion in the systematic review. Among these, three studies allowed calculation of risk ratios for immediate PPB and five studies allowed calculation of risk ratios for delayed PPB. Figures 1-3 summarises outcomes for each individual study, while Table 1 summarises the pooled results of the meta-analysis.
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Figure 1.
Continued clopidogrel and immediate and delayed post-polypectomy bleed. Events = immediate and delayed post-polypectomy bleed.
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Figure 2.
Continued clopidogrel and immediate post-polypectomy bleed. Events = immediate post-polypectomy bleed.
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Figure 3.
Continued clopidogrel and delayed post-polypectomy bleed. Events = delayed post-polypectomy bleed.
Characteristics of all eligible studies are outlined in Table S1. All studies included patients referred for elective colonoscopy. Feagins et al. continued ASA therapy in both the continued clopidogrel group and the control group, and stopped clopidogrel 5 days prior to polypectomy in the control group. 78.8% of clopidogrel users were on concomitant ASA compared to 27.9% of controls (P = 0.64). Rodino et al. included patients on both low-dose acetylsalicylic acid (ASA) and clopidogrel with recent coronary stenting for myocardial infarction in the past one year, and all subjects remained on continued ASA therapy during the time of polypectomy. Singh et al. continued ASA therapy in all patients, with 54% of patients in the continued clopidogrel group and 32% of controls receiving concomitant ASA therapy. Feagins and Iqbal continued ASA therapy in all patients, with 87.8% of patients in the continued thienopyridine group and 40.1% of controls. Indications for thienopyridine usage included 82.2% with a coronary stent, 3.2% with a peripheral stent, 1.4% with both a coronary and peripheral stent, 8.7% with coronary artery disease (with or without coronary artery bypass graft), 4.6% for cerebral vascular accident or transient ischaemic attack, and 0.5% who were allergic to ASA. The remaining study did not mention specifically concomitant ASA use. Four studies defined delayed PPB as clinically significant observed bleeding within 30 days or 4 weeks of polypectomy, while Rodino et al. defined delayed PPB as clinically significant observed bleeding within 15 days of polypectomy.
We assessed the quality of included studies using the Newcastle-Ottawa quality assessment scales. A score ≥5 was considered adequate quality for inclusion. Overall, the quality of studies was high. Three studies scored 8 points, one study scored 7 points, one study scored 5 points. There was no publication bias detected in comparing immediate and delayed post-polypectomy bleeding in patients on continued clopidogrel therapy, respectively, based on the symmetry of the funnel plots.
Five observational studies met inclusion criteria with 574 subjects on continued clopidogrel therapy and 6169 controls (Figure 1). Of 574 subjects who continued clopidogrel, 37 (6.45%) experienced PPB vs. 103 of 6169 controls (1.67%). The pooled RR for PPB on continued clopidogrel therapy was 2.54 (95% CI 1.68–3.84, P < 0.00001, I = 2%) suggesting an increase in PPB. Sensitivity analysis revealed that findings remained statistically significant after removal of each individual study.
Three observational studies that assessed immediate PPB met inclusion criteria, with 431 subjects on continued clopidogrel and 3920 controls (Figure 2). Immediate PPB was observed in 22 of 431 on clopidogrel (5.1%) vs. 66 of 3920 (1.68%) controls, with a nonsignificant pooled RR of 1.76 (95% CI 0.90–3.46, P = 0.10, I = 30%). PPB sensitivity analysis demonstrated similar results when each individualised study was removed.
Five observational studies that assessed delayed PPB met inclusion criteria with 565 subjects on continued clopidogrel and 6158 controls (Figure 3). Delayed PPB was observed in 15 of the 565 on clopidogrel (2.65%) vs. 37 of 6158 (0.6%) controls, with a significant pooled RR of 4.66 (95% CI 2.37–9.17, P < 0.00001, I = 0%). Sensitivity analysis demonstrated that removal of the subjects from Singh et al. increased the RR to 5.62 (95% CI 2.29–13.82, P = 0.0002), and removal of the subjects from Grossman et al. decreased the RR to 3.93 (95% CI 1.74–8.89, P = 0.001). However, the pooled RR remained significant with removal of each individual study.
Results
Search Results
Our search strategy yielded 151 studies, of which 127 were excluded on review of the title and abstract. A further 19 studies were excluded after careful review of the full text. Where only partial information on the outcomes of interest was reported in the article, the authors were contacted and asked to provide additional information. Using a questionnaire, Waters et al. assessed the risk of cardiovascular events and PPB in patients who continued/discontinued clopidogrel prior to polypectomy. The authors could not provide specific results for inclusion in our meta-analysis. Two abstracts were excluded by Feagins and colleagues, as the subjects were part of larger data sets of studies included in this meta-analysis.
Overall, five studies were eligible for inclusion in the systematic review. Among these, three studies allowed calculation of risk ratios for immediate PPB and five studies allowed calculation of risk ratios for delayed PPB. Figures 1-3 summarises outcomes for each individual study, while Table 1 summarises the pooled results of the meta-analysis.
(Enlarge Image)
Figure 1.
Continued clopidogrel and immediate and delayed post-polypectomy bleed. Events = immediate and delayed post-polypectomy bleed.
(Enlarge Image)
Figure 2.
Continued clopidogrel and immediate post-polypectomy bleed. Events = immediate post-polypectomy bleed.
(Enlarge Image)
Figure 3.
Continued clopidogrel and delayed post-polypectomy bleed. Events = delayed post-polypectomy bleed.
Characteristics of Included Studies
Characteristics of all eligible studies are outlined in Table S1. All studies included patients referred for elective colonoscopy. Feagins et al. continued ASA therapy in both the continued clopidogrel group and the control group, and stopped clopidogrel 5 days prior to polypectomy in the control group. 78.8% of clopidogrel users were on concomitant ASA compared to 27.9% of controls (P = 0.64). Rodino et al. included patients on both low-dose acetylsalicylic acid (ASA) and clopidogrel with recent coronary stenting for myocardial infarction in the past one year, and all subjects remained on continued ASA therapy during the time of polypectomy. Singh et al. continued ASA therapy in all patients, with 54% of patients in the continued clopidogrel group and 32% of controls receiving concomitant ASA therapy. Feagins and Iqbal continued ASA therapy in all patients, with 87.8% of patients in the continued thienopyridine group and 40.1% of controls. Indications for thienopyridine usage included 82.2% with a coronary stent, 3.2% with a peripheral stent, 1.4% with both a coronary and peripheral stent, 8.7% with coronary artery disease (with or without coronary artery bypass graft), 4.6% for cerebral vascular accident or transient ischaemic attack, and 0.5% who were allergic to ASA. The remaining study did not mention specifically concomitant ASA use. Four studies defined delayed PPB as clinically significant observed bleeding within 30 days or 4 weeks of polypectomy, while Rodino et al. defined delayed PPB as clinically significant observed bleeding within 15 days of polypectomy.
We assessed the quality of included studies using the Newcastle-Ottawa quality assessment scales. A score ≥5 was considered adequate quality for inclusion. Overall, the quality of studies was high. Three studies scored 8 points, one study scored 7 points, one study scored 5 points. There was no publication bias detected in comparing immediate and delayed post-polypectomy bleeding in patients on continued clopidogrel therapy, respectively, based on the symmetry of the funnel plots.
Colonoscopic Post-polypectomy Bleeding
Five observational studies met inclusion criteria with 574 subjects on continued clopidogrel therapy and 6169 controls (Figure 1). Of 574 subjects who continued clopidogrel, 37 (6.45%) experienced PPB vs. 103 of 6169 controls (1.67%). The pooled RR for PPB on continued clopidogrel therapy was 2.54 (95% CI 1.68–3.84, P < 0.00001, I = 2%) suggesting an increase in PPB. Sensitivity analysis revealed that findings remained statistically significant after removal of each individual study.
Immediate Post-polypectomy Bleeding
Three observational studies that assessed immediate PPB met inclusion criteria, with 431 subjects on continued clopidogrel and 3920 controls (Figure 2). Immediate PPB was observed in 22 of 431 on clopidogrel (5.1%) vs. 66 of 3920 (1.68%) controls, with a nonsignificant pooled RR of 1.76 (95% CI 0.90–3.46, P = 0.10, I = 30%). PPB sensitivity analysis demonstrated similar results when each individualised study was removed.
Delayed Post-polypectomy Bleeding
Five observational studies that assessed delayed PPB met inclusion criteria with 565 subjects on continued clopidogrel and 6158 controls (Figure 3). Delayed PPB was observed in 15 of the 565 on clopidogrel (2.65%) vs. 37 of 6158 (0.6%) controls, with a significant pooled RR of 4.66 (95% CI 2.37–9.17, P < 0.00001, I = 0%). Sensitivity analysis demonstrated that removal of the subjects from Singh et al. increased the RR to 5.62 (95% CI 2.29–13.82, P = 0.0002), and removal of the subjects from Grossman et al. decreased the RR to 3.93 (95% CI 1.74–8.89, P = 0.001). However, the pooled RR remained significant with removal of each individual study.
