The colorectal cancer represents a significant global public health burden, ranking as the third most common malignancy in both incidence and mortality (Sung et al., 2021). Consequently, mitigating its lethal impact is imperative. With the rapid evolution of early screening for colorectal carcinoma, colonoscopic procedures are becoming increasingly popular due to their potential effectiveness in reducing the incidence and mortality of colorectal cancer (Zauber et al., 2012; Amato et al., 2016). However, it is complicated that the common complication is postoperative bleeding, particularly among patients prescribed antiplatelet medications (Yanagisawa et al., 2018). Antiplatelet agents, including aspirin and P2Y12 inhibitors such as clopidogrel, prasugrel, ticagrelor, and cilostazol, are commonly used for thrombosis prevention in cardiovascular and cerebrovascular diseases. Hemorrhage is a major complication associated with antiplatelet therapy. Patients who take antiplatelet agents face a higher bleeding risk compared to those who are not on antiplatelet agents (Pig et al., 2018). It is reported that clopidogrel is associated with an increased the risk of post-polypectomy bleeding (PPB), but aspirin does not (Gandhi et al., 2013). Therefore, ensuring safe conditions during colonoscopy for patients on antiplatelet therapy has become increasingly important (Kim et al., 2019). Nevertheless, the optimal management of antiplatelet therapy around colonoscopy, whether to continue or discontinue, remains uncertain.

The management of antiplatelet therapy in patients undergoing colonoscopy has been debated for several years. However, the available data on whether antiplatelet agents increase bleeding risk and whether cessation is necessary before polypectomy are still limited and conflicting (Manocha et al., 2012; Pan et al., 2012). Current guidelines have emerged regarding the management of antiplatelet therapy for patients undergoing colonoscopy. American guidelines suggest interrupting P2Y12i before colonoscopy in patients with low cardiovascular risk, while continuing therapy in those with high cardiovascular risk, but aspirin should not be interrupted (Committee et al., 2016). European guidelines recommend interrupting P2Y12i 7 days prior to colonoscopy in patients with low cardiovascular risk, whereas consensus among cardiologists is suggested for those at high cardiovascular risk (Veitch et al., 2021a). Nevertheless, the quality of evidence supporting these recommendations ranges from moderate to low. Furthermore, the clinical practice regarding the management of antithrombotics vary widely among colonoscopy clinicians (Kadakia et al., 1996). We must balance the risk of post-polypectomy bleeding against the thromboembolic risk of interrupting antiplatelet therapy (Telford and Abraham, 2022). The proper antiplatelet management around polypectomy should minimize post-procedural bleeding risk bleeding and thromboembolic risks. Therefore, there is an urgent need for high-quality evidence to guide its optimal management.

We performed this systematic review to assess the risks of post-polypectomy bleeding and thromboembolic events in patients receiving uninterrupted antiplatelet therapy compared to those receiving interrupted antiplatelet therapy. Additionally, we aimed to identify potential sources of risk based on patient age, sample size, and geographical region. By synthesizing the available evidence, our objective was to highlight any knowledge gaps and provide direction for future research.

This study was performed in accordance with the Systematic Reviews and Meta- analyses (PRISMA) guidelines using a predetermined protocol (PROSPERO: CRD 42024544924).

This study comprehensively evaluates the bleeding and thromboembolic risk in patients undergoing colonoscopic polypectomy while receiving uninterrupted or interrupted antiplatelet therapy. Our findings indicate that there is no significant increase in the risk of post-polypectomy bleeding among patients on uninterrupted antiplatelet therapy compared to those on interrupted therapy. However, it is important to underline that elderly patients have an elevated risk of PPB. It should be noted that limited studies provided data on subgroups due to inadequate sample sizes.

Several meta-analyses have evaluated the risk of colonoscopic post-polypectomy bleeding in patients receiving antiplatelet therapy. However, these studies have yielded contradictory conclusions (Gandhi et al., 2013; Pig et al., 2018; Li et al., 2020). Among these studies, only one systematic review assessed the bleeding risk specially in patients on single antiplatelet therapy. Furthermore, none of these studies have systematically assessed thromboembolic risk associated with antiplatelet therapy. Thus, there is still limited data comparing the risk of bleeding and thromboembolism between individuals who discontinue or continue taking antiplatelet agents prior to polypectomy. Unlike previous studies that solely focused on bleeding risk, we simultaneously evaluated the risk of thromboembolism. Although uninterrupted antiplatelet therapy is associated with a high bleeding risk, aspirin withdrawal increased risk of cardiovascular adverse events (Biondi-Zoccai et al., 2006). Additionally, current guidelines regarding interruption or continuation of antiplatelet therapy are mainly based on expert opinion with weak evidence (Abdel et al., 2014). Notably, few therapeutic indications for single antiplatelet therapy are present in current cardiological guidelines (Collet et al., 2021; Ibanez et al., 2017). Henceforth, it is crucial to strike a balance between the risks posed by uninterrupted antiplatelet therapy for PPB and major adverse cardiovascular events before colonoscopic polypectomy. The updated European Society of Gastrointestinal Endoscopy (ESGE) guideline recommends maintaining P2Y12 inhibitors therapy for low-risk procedures (Veitch et al., 2021b). Nevertheless, discontinuation of P2Y12 inhibitors is advised for high-risk procedures. Notably, prior research demonstrate that thromboembolic events may manifest as early as 7 days following clopidogrel withdrawal (Eisenberg et al., 2009). Consequently, the decision to discontinue clopidogrel therapy warrants careful reconsideration, particularly in patients with elevated thrombotic risk.

Clopidogrel, a P2Y12 inhibitor, is widely utilized in the management of patients with coronary syndrome events and stroke (Gerhard-Herman et al., 2017; Kernan et al., 2014). Previous investigations have explored whether temporary discontinuation of clopidogrel should be considered for patients undergoing colonoscopy. However, these studies have yielded conflicting findings regarding increased bleeding risk (Feagins et al., 2013; Singh et al., 2010) or no excessive bleeding risk (Feagins et al., 2011). Some studies have reported a low incidence of post-polypectomy bleeding among patients who continued clopidogrel therapy through the period of polypectomy (Chan et al., 2019; Won et al., 2019). Our results are in line with these studies as we observed a low rate of bleeding and no significant difference in the occurrence of post-polypectomy bleeding between uninterrupted and interrupted subjects. Nevertheless, we observed a significantly increased risk of post-polypectomy bleeding in elderly patients receiving continued clopidogrel treatment. This can primarily be attributed to older individuals tend to be at higher bleeding risk due to comorbid medical conditions and multiple medications which may alter metabolism and excretion of antiplatelet drugs (Abraham, 2020). Additionally, advanced age has been recognized as an important factor predicting post-polypectomy bleeding, and increasing the likelihood of receiving blood transfusions (Sorbi et al., 2000). For elderly patients, therapeutic decision-making regarding P2Y12 inhibitors continuation requires particular caution. Given the inherent complexity of balancing thrombotic and bleeding risks, it should be recommended liaising with the consultant interventional cardiologists about the risk/benefit of discontinuing P2Y12 inhibitors. One study indicated that a greater proportion of patients who continued taking clopidogrel experienced post-polypectomy bleeding (Kishino et al., 2020). However, it is important to underline that post-polypectomy bleeding is rarely life threatening, thrombotic event caused by clopidogrel interruption may be harmful. Therefore, further deliberation about the balance between bleeding risk and cardiovascular thrombotic events when interrupting antiplatelet therapy is essential (Sonneveld et al., 2019; Radaelli et al., 2019).

Aspirin has been widely used in clinical practice for the prevention of thrombosis worldwide. Generally, there is no need to discontinue aspirin prior to polypectomy due to low risk of post-polypectomy bleeding (Yousfi et al., 2004). The Japanese guideline does not recommend discontinuation of aspirin therapy before colonoscopic polypectomy procedures (Fujimoto et al., 2014). A study reported no significant difference in the incidence of post-polypectomy bleeding between patients who continued or stopped aspirin (Yousfi et al., 2004). However, caution should be exercised when removing large colonic polyps (Feagins et al., 2013). It is important to note that advanced age independently increases the risk of bleeding in patients undergoing colonoscopic polypectomy (Committee et al., 2016; Veitch et al., 2021a). Our study is in line with these data, uninterrupted aspirin therapy do not increase bleeding risk compared to interrupted use during colonoscopy, but a high risk of post-polypectomy bleeding was observed in elderly patients. Literature reported that elderly patients over 75 years were more likely to require re-hospitalization within 7 days after colonoscopy (Grossberg et al., 2020), primarily due to their multiple comorbidities such as cardiovascular disease in antithrombotic treatment, especially antiplatelet therapy (Heitman et al., 2009; O'Brien et al., 2019).

Physicians often prioritize the risk of post-polypectomy bleeding due to its immediate occurrence, while stroke may manifest later and potentially go unnoticed by the performing physician during colonoscopy (Alonso-Coello et al., 2015; Doorey et al., 2018). Especially in high-risk patients, thrombosis resulting from temporary cessation of antiplatelet may be fatal. Therefore, a collaborative evaluation of bleeding and thromboembolism risk is essential to determine an appropriate treatment regimen. Current guidelines in the U.S. and Europe recommend withholding clopidogrel for 7 days prior to colonoscopic polypectomy (Committee et al., 2016; Veitch et al., 2016). However, it has been reported that thromboembolic events can occur as early as 7 days after interrupting clopidogrel (Eisenberg et al., 2009). Our findings also indicated an increased incidence of thromboembolic events with interrupted clopidogrel therapy. Therefore, it is important to consider the potential elevated risk of thromboembolic events in patients on uninterrupted antiplatelet therapy. However, existing evidence regarding thromboembolic risk remains limited due to a scarcity of studies. In particular, there is a lack of studies comparing risk of thromboembolism between patients continuing antiplatelet therapy versus those discontinue it. Thus, it is important to generate stronger data concerning bleeding and thromboembolism risks in patients receiving antiplatelet therapy.

Currently, no randomized controlled trials (RCTs) have directly compared bleeding and thromboembolic risks between uninterrupted and interrupted antiplatelet therapy in patients undergoing polypectomy. Furthermore, existing evidence regarding antiplatelet management in this population remains inconclusive (Abdel et al., 2014; Collet et al., 2021). To address this gap, we conducted a systematic review to evaluate these trade-offs in real-world clinical practice. Our findings suggest that continuing antiplatelet therapy may be acceptable, however, elderly patients on uninterrupted regimens demonstrated an elevated bleeding risk. Future studies are warranted to determine optimal management strategy for antiplatelet therapy in this clinical context.

This study provides real-world data on the risk of post-colonoscopy bleeding and thromboembolism with a large sample size, thereby enhancing the reliability of evidence. However, several limitations exist in this study. Firstly, due to the unavailability of RCTs evaluating bleeding and thromboembolic risk on antiplatelet therapy, only observational studies were included, which may undermine the value of extrapolating these results to clinical practice. Although observational studies are often considered methodologically weaker than RCTs due to potential confounding, they are increasingly recognized as complementary (Jarow et al., 2017). By extending the findings to larger, real-world patient populations, observational studies and their meta-analyses provide decision-makers with evidence that is broadly applicable. Secondly, our study solely focused on assessing the risk of delayed bleeding due to its unpredictable nature and potential serious consequences, in contrast to the easily detectable and controllable immediate bleeding following colonoscopic polypectomy. Thirdly, our study assessed bleeding risk among patients on single clopidogrel and aspirin, and not any performed sub-analysis among other antiplatelet agents due to no available data. Fourthly, although risk of post-polypectomy bleeding has been reported to be associated with polyp size, location, and the types of medications (Feagins et al., 2019; Kothari et al., 2019; Aiza et al., 2022), these variables were not considered in our included studies due to data absence. Additionally, given the limited number of patients undergoing polypectomy while on dual antiplatelet therapy, we did not explore these cases, but plan to investigate them in future studies. Finally, the generalizability of our findings in subgroups may be constrained by the limited number of studies.

In summary, the incidence of colonoscopic post-polypectomy bleeding was comparable between uninterrupted and interrupted antiplatelet users, whereas a higher risk of bleeding was observed in elderly patients on uninterrupted antiplatelet therapy. Patients receiving interrupted clopidogrel had an increased risk of thromboembolism compared to those receiving uninterrupted clopidogrel. Therefore, the continuation of antiplatelet therapy may be acceptable for colonoscopic polypectomy, but caution should be exercised in elderly patients with a high risk of adverse cardiovascular events. In future, randomized controlled studies are necessary to further elucidate the issue surrounding antiplatelet use during polypectomy.