Pharmacological Prophylaxis Against Post-ERCP Pancreatitis
Pharmacological Prophylaxis Against Post-ERCP Pancreatitis
Background The efficacy of many pharmacological agents for preventing post-ERCP pancreatitis (PEP) has been evaluated in randomised controlled trials (RCTs), but it is unclear which agent(s) should be used in clinical practice. Network meta-analyses of RCTs are used to simultaneously compare several agents to determine their relative efficacy and identify priority agents for comparison in future RCTs.
Aim To evaluate pharmacological agents for the prevention of PEP by conducting a network meta-analysis of RCTs.
Methods We searched MEDLINE, EMBASE and Cochrane Library databases for RCTs that evaluated the efficacy of agents for preventing PEP. RCTs were simultaneously analysed using random-effects network meta-analysis under the Bayesian framework to identify the best agents. The efficacy of agents was ordered according to the probability of being ranked as any of the top three best performing agents.
Results The network meta-analysis included 99 RCTs evaluating 16 agents in 25 313 patients. Topical epinephrine (adrenaline) was the most efficacious agent with 85.9% probability of ranking among the top three agents, followed by nafamostat (51.4%), antibiotics (44.5%) and NSAIDs (42.8%). However, in a sensitivity analysis including only rectal NSAIDs, NSAIDs moved from fourth rank to second (58.1%). Patients receiving topical epinephrine, compared with placebo, had a 75% reduced risk of PEP (OR 0.25, 95% probability interval 0.06–0.66).
Conclusions Topical epinephrine and rectal NSAIDs are the most efficacious agents for preventing post-ERCP pancreatitis, based on existing RCTs. Combinations of these agents, which act on different steps in the pathogenesis of post-ERCP pancreatitis, should be evaluated in future trials.
Post-ERCP pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an estimated incidence of 3–7% among average-risk patients and 15–20% among patients at high risk for developing PEP. There has been an interest in the pharmacological prevention of PEP since 1977, when randomised controlled trials (RCTs) using aprotinin and calcitonin were published.
Only one of three professional societies with guidelines has recommended a pharmacological agent for PEP prophylaxis. The Japanese Guidelines (JPN) and American Society of Gastrointestinal Endoscopy have emphasised the lack of efficacy of certain pharmacological agents to prevent PEP, but they have not advocated in favour of any single pharmacological agent. However, the 2010 guidelines of the European Society of Gastrointestinal Endoscopy recommended rectal NSAIDs for the prevention of PEP based on five placebo-controlled RCTs. A landmark multicentre RCT published in 2012 also demonstrated the superiority of rectal NSAIDs over placebo in high-risk patients.
While seven RCTs have demonstrated the efficacy of rectal NSAIDs, these were all compared with placebo and it is unknown if rectal NSAIDs are better for the prevention of PEP when compared with other pharmacological agents studied in RCTs. Given the lack of head-to-head RCTs between the numerous pharmacological agents studied for PEP prophylaxis, statistical techniques, such as network meta-analyses (NMAs), can be used to perform direct and indirect comparisons of agents evaluated in prior RCTs to determine which agent(s) is(are) most efficacious for preventing PEP. The objective of this study was to conduct a NMA of RCTs of pharmacological agents for preventing PEP among patients undergoing ERCP.
Abstract and Introduction
Abstract
Background The efficacy of many pharmacological agents for preventing post-ERCP pancreatitis (PEP) has been evaluated in randomised controlled trials (RCTs), but it is unclear which agent(s) should be used in clinical practice. Network meta-analyses of RCTs are used to simultaneously compare several agents to determine their relative efficacy and identify priority agents for comparison in future RCTs.
Aim To evaluate pharmacological agents for the prevention of PEP by conducting a network meta-analysis of RCTs.
Methods We searched MEDLINE, EMBASE and Cochrane Library databases for RCTs that evaluated the efficacy of agents for preventing PEP. RCTs were simultaneously analysed using random-effects network meta-analysis under the Bayesian framework to identify the best agents. The efficacy of agents was ordered according to the probability of being ranked as any of the top three best performing agents.
Results The network meta-analysis included 99 RCTs evaluating 16 agents in 25 313 patients. Topical epinephrine (adrenaline) was the most efficacious agent with 85.9% probability of ranking among the top three agents, followed by nafamostat (51.4%), antibiotics (44.5%) and NSAIDs (42.8%). However, in a sensitivity analysis including only rectal NSAIDs, NSAIDs moved from fourth rank to second (58.1%). Patients receiving topical epinephrine, compared with placebo, had a 75% reduced risk of PEP (OR 0.25, 95% probability interval 0.06–0.66).
Conclusions Topical epinephrine and rectal NSAIDs are the most efficacious agents for preventing post-ERCP pancreatitis, based on existing RCTs. Combinations of these agents, which act on different steps in the pathogenesis of post-ERCP pancreatitis, should be evaluated in future trials.
Introduction
Post-ERCP pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an estimated incidence of 3–7% among average-risk patients and 15–20% among patients at high risk for developing PEP. There has been an interest in the pharmacological prevention of PEP since 1977, when randomised controlled trials (RCTs) using aprotinin and calcitonin were published.
Only one of three professional societies with guidelines has recommended a pharmacological agent for PEP prophylaxis. The Japanese Guidelines (JPN) and American Society of Gastrointestinal Endoscopy have emphasised the lack of efficacy of certain pharmacological agents to prevent PEP, but they have not advocated in favour of any single pharmacological agent. However, the 2010 guidelines of the European Society of Gastrointestinal Endoscopy recommended rectal NSAIDs for the prevention of PEP based on five placebo-controlled RCTs. A landmark multicentre RCT published in 2012 also demonstrated the superiority of rectal NSAIDs over placebo in high-risk patients.
While seven RCTs have demonstrated the efficacy of rectal NSAIDs, these were all compared with placebo and it is unknown if rectal NSAIDs are better for the prevention of PEP when compared with other pharmacological agents studied in RCTs. Given the lack of head-to-head RCTs between the numerous pharmacological agents studied for PEP prophylaxis, statistical techniques, such as network meta-analyses (NMAs), can be used to perform direct and indirect comparisons of agents evaluated in prior RCTs to determine which agent(s) is(are) most efficacious for preventing PEP. The objective of this study was to conduct a NMA of RCTs of pharmacological agents for preventing PEP among patients undergoing ERCP.