Comparative stroke risk of antiepileptic drugs in patients with epilepsy

Authors

  • Cheng-Yang Hsieh,

    1. Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
    2. Department of Neurology, Tainan Sin Lau Hospital, Tainan, Taiwan
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  • Edward Chia-Cheng Lai,

    1. Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
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  • Yea-Huei Kao Yang,

    1. Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
    2. Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan
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  • Swu-Jane Lin

    1. Department of Pharmacy Administration, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, U.S.A.
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  • Edward Chia-Cheng Lai and Cheng-Yang Hsieh are contributed equally to this work.

Address correspondence to Yea-Huei Kao Yang, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1, University Road, 701, Tainan, Taiwan. E-mail:yhkao@mail.ncku.edu.tw

Summary

Purpose:  Patients with epilepsy have higher stroke-related morbidity and mortality, leading to the suspicion that the increased stroke events may be associated with antiepileptic drug (AED) exposure. We evaluated the comparative risk of stroke in adult patients with epilepsy receiving phenytoin (PHT), valproic acid (VPA), or carbamazepine (CBZ) to help determine the stroke risk for Asian patients with specific AED exposure.

Methods:  We conducted a population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database (NHIRD). The cohort consists of adult patients with epilepsy who were new to PHT, CBZ, or VPA monotherapy and without prior stroke history. Patients were followed for 5 years. The event of interest was a hospitalization or emergency visit due to stroke. Cox proportional hazard models were used to estimate the comparative risk of AEDs. Subanalyses included an evaluation of different subtypes of stroke, the propensity score matched technique, the intention-to-treat approach, and stratification analyses.

Key Findings:  Patients receiving PHT had a significantly higher stroke risk (adjusted hazard ratio [HR] 1.72; 95% confidence interval [CI] 1.20–2.47), followed by VPA (adjusted HR 1.27; 95% CI 0.78–2.07), when compared with CBZ. The results of all subanalyses showed a consistent trend of higher stroke risk with PHT use. In addition, there appeared to be a dose–response relationship between stroke risk and PHT prescriptions.

Significance:  The stroke risk was higher in PHT but not significantly different in VPA as compared to CBZ. Physicians should reconsider using PHT for patients with epilepsy who already have a higher risk of stroke.

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