Aprotinin and the risk of death and renal dysfunction in patients undergoing cardiac surgery: a meta-analysis of epidemiologic studies

Authors

  • Joshua J. Gagne PharmD, MS,

    Corresponding author
    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
    • Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA.
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  • Donald E. G. Griesdale MD, MPH,

    1. Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, BC, Canada
    2. Department of Anesthesia & Program of Critical Care Medicine, Vancouver General Hospital, Vancouver, BC, Canada
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  • Sebastian Schneeweiss MD, ScD

    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
    2. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
    3. Harvard Medical School, Boston, MA, USA
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  • This research was presented at the 24th International Conference on Pharmacoepidemiology and Therapeutic Risk Management, Copenhagen, Denmark, August 2008. Dr Schneeweiss has served as consultant to i3 Drug Safety which contracted with Bayer to study the safety of aprotinin.

Abstract

Purpose

Observational studies have reported conflicting results regarding aprotinin's risk of renal dysfunction and death. A meta-analysis was conducted to summarize results and explain variation of published epidemiologic studies on risks of renal dysfunction and death associated with aprotinin.

Methods

MEDLINE and EMBASE were systematically searched for non-experimental studies that reported risk of renal dysfunction or death with aprotinin use during cardiac surgery in adults. Random-effects meta-analyses were used to pool results across studies for each outcome. Stratified and meta-regression analyses were used to identify sources of heterogeneity.

Results

Eleven relevant studies were identified and included in the analysis, including 10 that reported renal dysfunction and seven that reported death. Aprotinin was associated with renal dysfunction (risk ratio (RR), 1.42; 95%CI 1.13–1.79) and long-term mortality (hazard ratio (HR) 1.22; 95%CI 1.08–1.39). Pooled estimates were lower for short-term mortality (RR 1.16; 95%CI 0.84–1.58) and renal failure requiring dialysis (RR 1.17; 95%CI 0.99–1.38). Cardiopulmonary bypass (CPB) time, which may be on the causal pathway, was a significant source of heterogeneity, with a 29% increased risk of renal dysfunction for every 10 minute increase in CPB time (p = 0.03).

Conclusions

Despite some studies that reported no association between aprotinin and renal outcomes during cardiac surgery, the totality of epidemiologic evidence indicates an increased risk that cannot be fully explained by need for transfused red blood cells (RBCs). Epidemiologic studies also suggest an increased risk of long-term mortality associated with aprotinin as compared to various comparators used in these studies, although residual confounding cannot be ruled out. Copyright © 2009 John Wiley & Sons, Ltd.

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