Effect of Statin Intensity on the Risk of Epilepsy After Ischaemic Stroke: Real-World Evidence from Population-Based Hea
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ORIGINAL RESEARCH ARTICLE
Effect of Statin Intensity on the Risk of Epilepsy After Ischaemic Stroke: Real-World Evidence from Population-Based Health Claims Fang-Ju Lin1,2,3 • Hung-Wei Lin1 • Yunn-Fang Ho1,2,3
Ó Springer International Publishing AG, part of Springer Nature 2018
Abstract Background Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited. Objective The association between statin use, including timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003–2013). Methods Patients with new-onset ischaemic stroke were identified. The main outcome was a diagnosis of epilepsy after ischaemic stroke. According to pre-stroke statin use, groups of current users, former users, and non-users were compared using ANOVA. An extended Cox regression model was utilized to estimate the hazard ratio (HR) of PSE, with post-stroke statin use and certain comedications as time-dependent variables. Serial sensitivity analyses were performed to ensure study robustness.
Results Of the 20,858 ischaemic stroke patients, 954 (4.6%) developed PSE. Post-stroke statin use (adjusted HR (aHR) 0.55; 95% confidence interval 0.46–0.67, p\0.001), but not pre-stroke statin use was associated with a significantly reduced risk of developing PSE. A dose-response correlation was also observed between PSE risk reduction and quartiles of the statin cumulative defined daily dose (cDDD) (aHR 0.84, 0.67, 0.53, and 0.50 for the lowest, second, third, and highest quartiles of cDDD, respectively). Risk predictors and protectors against PSE were also characterized. Conclusion The post-stroke use of statins after ischaemic stroke was associated with PSE risk reduction in a cDDDdependent manner. Further clinical studies on the potential applications of statins for PSE prophylaxis, particularly among at-risk patients, are warranted.
Key Points This study was partially presented at the 45th European Society of Clinical Pharmacy, 5–7 October, 2016, in Oslo, Norway.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40263-018-0501-0) contains supplementary material, which is available to authorized users. & Yunn-Fang Ho [email protected] 1
Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, No. 33, Lin-Sen S. Rd., Taipei 10050, Taiwan
2
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
3
Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan
This study showed robust associations between a reduced risk of developing post-stroke epilepsy (PSE) and post-stroke statin use by analysing data from a nationwide database (2003–2013), using statin prescriptions, cumulative defined daily doses (cDDDs), and comedications as time-dependent covariates. Higher post-stroke cumulative statin doses were a
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