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Near-Real-Time Monitoring of New Drugs: An Application Comparing Prasugrel Versus Clopidogrel

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Abstract

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.

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Acknowledgments

This work was presented as a poster at the 28th International Conference on Pharmacoepidemiology and Therapeutic Risk Management, August 2012, Barcelona, Spain, and as a symposium presentation at the International Society for Pharmacoepidemiology Mid-Year Meeting, April 2013, Munich, Germany. Funded by the National Library of Medicine (RO1-LM010213), the National Center for Research Resources (RC1-RR028231), the National Heart Lung and Blood Institute (RC4-HL106373), and HealthCore Inc. through the Brigham-HealthCore Methods Development Collaboration. Dr. Rassen was supported by a career development award from the Agency for Healthcare Research and Quality (AHRQ) (K01-HS018088). Dr. Schneeweiss was the Principal Investigator of the Brigham and Women’s Hospital DEcIDE Center on Comparative Effectiveness Research and the DEcIDE Methods Center, both funded by the AHRQ. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Drs. Gagne, Rassen, and Schneeweiss are co-investigators of the FDA-funded Mini-Sentinel project (PI: Dr. Richard Platt); however, no FDA funding supported this research and the opinions expressed here are those of the authors and not necessarily of Mini-Sentinel or the FDA. Dr. Schneeweiss is PI of investigator-initiated grants from Pfizer, Novartis, and Boehringer-Ingelheim to the Brigham and Women’s Hospital. Dr. Bohn served as a consultant to Sanofi prior to the development of this manuscript. Dr. Sridhar is employee of HealthCore. Dr. Daniel was an employee of HealthCore during part of the study period. Ms. Patrick and Dr. Choudhry have no other relevant conflicts of interest to disclose.

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Authors and Affiliations

  1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA, 02120, USA

    Joshua J. Gagne, Jeremy A. Rassen, Niteesh K. Choudhry, Amanda R. Patrick, Jun Liu & Sebastian Schneeweiss

  2. Rhonda L. Bohn, LLC, Waban, MA, USA

    Rhonda L. Bohn

  3. HealthCore Inc, Wilmington, DE, USA

    Gayathri Sridhar

  4. The Engelberg Center for Health Care Reform, Brookings Institution, Washington, DC, USA

    Gregory W. Daniel

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  1. Joshua J. Gagne
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  2. Jeremy A. Rassen
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  3. Niteesh K. Choudhry
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  4. Rhonda L. Bohn
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  5. Amanda R. Patrick
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  6. Gayathri Sridhar
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  7. Gregory W. Daniel
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  8. Jun Liu
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  9. Sebastian Schneeweiss
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Corresponding author

Correspondence to Joshua J. Gagne.

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Gagne, J.J., Rassen, J.A., Choudhry, N.K. et al. Near-Real-Time Monitoring of New Drugs: An Application Comparing Prasugrel Versus Clopidogrel. Drug Saf 37, 151–161 (2014). https://doi.org/10.1007/s40264-014-0136-0

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