Replication of Mini-Sentinel Study Assessing Mirabegron and Cardiovascular Risk in Non-Mini-Sentinel Databases

BACKGROUND In 2014, the US Food and Drug Administration (FDA) initiated a prospective routine surveillance using the Mini-Sentinel (M-S) program to assess potential signals of acute myocardial infarction (AMI) and stroke with use of mirabegron, indicated for the treatment of overactive bladder (OAB), compared with oxybutynin. PURPOSE To replicate the FDA M-S analysis of mirabegron using datasets that did not contribute to the M-S program. METHODS IMS PharMetrics Plus and Truven MarketScan claims data from 2012-2015 were converted to the M-S Common Data Model. New and non-new users of mirabegron and oxybutynin were analyzed per the publicly available M-S protocol, and propensity score-matched 1:1 using the M-S PROMPT 2 module. Incidence rates (IR) were calculated per 1000 person-years (PY). Adjusted hazard ratios (aHRs) for mirabegron versus oxybutynin were calculated using Cox regression models. RESULTS In PharMetrics, 12,429 new mirabegron users and 61,548 new oxybutynin users were identified. The aHR was 0.67 (95% confidence interval (CI)] 0.33-1.37) for AMI (mirabegron IR 4.4/1000 PY), and 0.62 (95% CI 0.34-1.13) for stroke (mirabegron IR 6.3/1000 PY). In MarketScan, 17,182 new mirabegron users and 63,962 new oxybutynin users were identified. The aHR was 0.57 (95% CI 0.17-1.95) for AMI, and 0.69 (95% CI 0.30-1.62) for stroke; IRs were similar to those from PharMetrics. Neither dataset suggested an increased risk of AMI or stroke associated with mirabegron in non-new users. CONCLUSIONS Using the publicly-available M-S protocol and analysis programs with alternative (non M-S) data sources, no statistically significant increased risk of AMI or stroke was found among new or non-new users of mirabegron compared with oxybutynin. These findings were consistent with the FDA M-S mirabegron study.