Near-real-time monitoring of new drugs: an application comparing prasugrel versus clopidogrel.

BACKGROUND Methods for near-real-time monitoring of new drugs in electronic healthcare data are needed. OBJECTIVE In a novel application, we prospectively monitored ischemic, bleeding, and mortality outcomes among patients initiating prasugrel versus clopidogrel in routine care during the first 2 years following the approval of prasugrel. METHODS Using the HealthCore Integrated Research Database, we conducted a prospective cohort study comparing prasugrel and clopidogrel initiators in the 6 months following the introduction of prasugrel and every 2 months thereafter. We identified patients who initiated antiplatelets within 14 days following discharge from hospitalizations for myocardial infarction (MI) or acute coronary syndrome. We matched patients using high-dimensional propensity scores (hd-PSs) and followed them for ischemic (i.e., MI and ischemic stroke) events, bleed (i.e., hemorrhagic stroke and gastrointestinal bleed) events, and all-cause mortality. For each outcome, we applied sequential alerting algorithms. RESULTS We identified 1,282 eligible new users of prasugrel and 8,263 eligible new users of clopidogrel between September 2009 and August 2011. In hd-PS matched cohorts, the overall MI rate difference (RD) comparing prasugrel with clopidogrel was -23.1 (95 % confidence interval [CI] -62.8-16.7) events per 1,000 person-years and RDs were -0.5 (-12.9-11.9) and -2.8 (-13.2-7.6) for a composite bleed event outcome and death from any cause, respectively. No algorithms generated alerts for any outcomes. CONCLUSIONS Near-real-time monitoring was feasible and, in contrast to the key pre-marketing trial that demonstrated the efficacy of prasugrel, did not suggest that prasugrel compared with clopidogrel was associated with an increased risk of gastrointestinal and intracranial bleeding.