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Confounding by Indication in Retrospective Studies of Intracerebral Hemorrhage: Antiepileptic Treatment and Mortality

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Abstract

Introduction

Intracerebral hemorrhage (ICH) is a highly fatal disease with few proven treatments. Data to guide clinician decisions for therapies, including antiepileptic drugs (AED), are limited. Published studies on AED treatment in ICH have provided conflicting results. We investigated the effect of AED treatment on 90-day mortality after ICH in a large prospectively ascertained cohort.

Methods

We conducted a retrospective analysis of a prospectively assembled cohort of patients with ICH in the supratentorial regions, comparing 90-day mortality and modified Rankin Score among 543 patients treated with AED during hospitalization and 639 AED-free ICH. Supratentorial ICH location was categorized as lobar or deep hemispheric.

Results

Multivariate analysis demonstrated an association between AED treatment and reduced 90-day mortality in supratentorial ICH (OR = 0.62, 95 % CI 0.42–0.90, p = 0.01) and the subset of lobar ICH (OR = 0.49, 95 % CI 0.25–0.96, p = 0.04). When analyses were restricted to subjects surviving longer than 5 days from ICH, however, no association between AED treatment and a 90-day outcome, regardless of hemorrhage location (all p > 0.15), was detected, despite more than adequate power to detect the originally observed association.

Conclusion

These results suggest that AED treatment in acute ICH is not associated with 90-day mortality or outcome and that any detected association could arise by confounding by indication, in which the most severely affected patients are those in whom AEDs are prescribed. They provide a cautionary example of the limitations of drawing conclusions about treatment effects from observational data.

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Acknowledgments

This work was funded by the National Institute for Neurological Disease and Stroke RO1NS059727, NIH R01NS073344, NIH K23NS059774. The authors thank Shawn Murphy and Henry Chueh and the Partners Health Care Research Patient Data Registry group for facilitating use of their database.

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Authors and Affiliations

  1. Hemorrhagic Stroke Research Group, Massachusetts General Hospital, Boston, MA, USA

    Thomas W. K. Battey, Guido J. Falcone, Alison M. Ayres, Kristin Schwab, Anand Viswanathan, Kristen A. McNamara, Zora Y. DiPucchio, Steven M. Greenberg & Jonathan Rosand

  2. Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    Thomas W. K. Battey, Guido J. Falcone & Jonathan Rosand

  3. Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street CPZN 6818, Boston, MA, 02114, USA

    Thomas W. K. Battey, Guido J. Falcone & Jonathan Rosand

  4. Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA

    Kevin N. Sheth

  5. Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA

    Joshua N. Goldstein

Authors
  1. Thomas W. K. Battey
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  2. Guido J. Falcone
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  3. Alison M. Ayres
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  4. Kristin Schwab
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  5. Anand Viswanathan
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  6. Kristen A. McNamara
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  7. Zora Y. DiPucchio
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  8. Steven M. Greenberg
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  9. Kevin N. Sheth
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  10. Joshua N. Goldstein
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  11. Jonathan Rosand
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Corresponding author

Correspondence to Jonathan Rosand.

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Battey, T.W.K., Falcone, G.J., Ayres, A.M. et al. Confounding by Indication in Retrospective Studies of Intracerebral Hemorrhage: Antiepileptic Treatment and Mortality. Neurocrit Care 17, 361–366 (2012). https://doi.org/10.1007/s12028-012-9776-z

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  • DOI: https://doi.org/10.1007/s12028-012-9776-z

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