Investigating incoherence gives insight: clopidogrel is equivalent to extended-release dipyridamole plus aspirin in secondary stroke prevention

Abstract Objective To identify confounding factors that may explain the incoherence between direct and indirect evidence in a published analysis comparing extended-release dipyridamole (ERDP) plus aspirin to clopidogrel for the reduction of stroke. Study Design and Setting An existing analysis was updated with new studies from a systematic literature review. Clinicians reviewed the studies for potential confounders. Network meta-analyses were conducted including or excluding potential confounders, and were estimated based on direct, indirect, or a combination of direct and indirect evidence. Model fit was compared using the residual deviance and the deviance information criterion (DIC); node splitting was used to test for incoherence between the networks. Results Six trials and one meta-analysis were identified; aspirin dosage was identified as a potential confounder. The odds ratio (OR) for stroke of aspirin plus ERDP vs. clopidogrel based on indirect evidence without aspirin dosage adjustment is 0.85 (0.68–1.05); when accounting for the aspirin dose–response relationship it is 0.96 (0.73–1.25); and the direct evidence based on PRoFESS resulted in an OR of 1.02 (0.93–1.12). Conclusion When analyzing networks of evidence, attention should be paid to identifying and adjusting for potentially confounding factors. Investigating rather than ignoring inconsistency in the data set leads to clearer insight into relative efficacy.