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.
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.
Authors: Joshua J Gagne; Bruce Fireman; Patrick B Ryan; Malcolm Maclure; Tobias Gerhard; Sengwee Toh; Jeremy A Rassen; Jennifer C Nelson; Sebastian Schneeweiss Journal: Pharmacoepidemiol Drug Saf Date: 2012-01 Impact factor: 2.890
Authors: Peter M Wahl; Joshua J Gagne; Thomas E Wasser; Debra F Eisenberg; J Keith Rodgers; Gregory W Daniel; Marcus Wilson; Sebastian Schneeweiss; Jeremy A Rassen; Amanda R Patrick; Jerry Avorn; Rhonda L Bohn Journal: Drug Saf Date: 2012-05-01 Impact factor: 5.606
Authors: Joshua J Gagne; Jeremy A Rassen; Alexander M Walker; Robert J Glynn; Sebastian Schneeweiss Journal: Epidemiology Date: 2012-03 Impact factor: 4.822
Authors: Niteesh K Choudhry; Jerry Avorn; Robert J Glynn; Elliott M Antman; Sebastian Schneeweiss; Michele Toscano; Lonny Reisman; Joaquim Fernandes; Claire Spettell; Joy L Lee; Raisa Levin; Troyen Brennan; William H Shrank Journal: N Engl J Med Date: 2011-11-14 Impact factor: 91.245
Authors: Frederic S Resnic; Thomas P Gross; Danica Marinac-Dabic; Nilsa Loyo-Berrios; Sharon Donnelly; Sharon-Lise T Normand; Michael E Matheny Journal: JAMA Date: 2010-11-10 Impact factor: 56.272
Authors: J J Gagne; R J Glynn; J A Rassen; A M Walker; G W Daniel; G Sridhar; S Schneeweiss Journal: Clin Pharmacol Ther Date: 2012-05-16 Impact factor: 6.875