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Background: FFR is useful in defining the physiological significance of intermediate coronary stenosis and requires induction of maximal hyperemia and measurement of pressure proximal and distal to the stenosis. Hyperemia normally is induced by either IV or IC adenosine, a medication associated with short-term side effects. IV regadenoson and IC nitroprusside have been suggested as viable alternatives. This meta-analysis aims to identify all studies comparing use of intravenous (IV) regadenoson or intracoronary (IC) nitroprusside with IV adenosine to determine differences related to the agent utilized for assessment of fractional flow reserve (FFR).Methods: We searched PubMed, EMBASE, Web of Science, SCOPUS, ClinicalTrials.gov and the Cochrane Library databases for studies comparing IV regadenoson or IC nitroprusside to IV adenosine for FFR assessment. The main outcome was difference in mean FFR measurement. The main secondary outcomes were composite side-effect profile and reclassification of lesions.Results: Seven studies were included in the analysis, with a total of 375 patients. Compared to IV adenosine, there was no difference in the mean FFR derived from IV regadenoson (p=1.0) or IC nitroprusside (p=0.48). IV regadenoson was associated with 53% lower risk of pooled side effects compared to IV adenosine (p=0.05). IC nitroprusside was associated with 97% lower risk of pooled side effects compared to IV adenosine (p<0.001).Conclusions: IV regadenoson and IC nitroprusside produce similar pressure-derived FFR measurements compared to IV adenosine and have a favorable side effect profile. Both can be considered as alternative agents to IV adenosine for FFR measurement. Further clinical validation is warranted. [ABSTRACT FROM AUTHOR]