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12 April 2023
Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study
),
Xue-Yan CUI1(
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Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations.
In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs’ safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs’ relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively.
81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count.
In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.
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Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study
), Xue-Yan CUI1(
)
Abstract
Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations.
In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs’ safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs’ relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively.
81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count.
In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.
References(17)
Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. Circulation 2020; 141: e139−e596.
Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol 2019; 18: 394−405.
Peng B, Wu B. [Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018]. Chin J Neurol 2018; 51: 666−682. [In Chinese].
Wang S, Ma F, Huang L, et al. Dl-3-n-butylphthalide (NBP): a promising therapeutic agent for ischemic stroke. CNS Neurol Disord Drug Targets 2018; 17: 338−347.
Watanabe K, Tanaka M, Yuki S, et al. How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis? J Clin Biochem Nutr 2018; 62: 20−38.
Ren Y, Wei B, Song X, et al. Edaravone’s free radical scavenging mechanisms of neuroprotection against cerebral ischemia: review of the literature. Int J Neurosci 2015; 125: 555−565.
Chen C, Li M, Lin L, et al. Clinical effects and safety of edaravone in treatment of acute ischaemic stroke: a meta-analysis of randomized controlled trials. J Clin Pharm Ther 2021; 46: 907−917.
Public Policy Committee, International Society of Pharmacoepidemiology. Guidelines for good pharmacoepidemiology practice (GPP). Pharmacoepidemiol Drug Saf 2016; 25: 2−10.
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310: 2191−2194.
Tian J, Lei P, He Y, et al. Absorption, distribution, metabolism, and excretion of [14C]NBP (3-n-butylphthalide) in rats. J Chromatogr B Analyt Technol Biomed Life Sci 2021; 1181: 122915.
Ma L, Sun J, Peng Y, et al. Glucuronidation of edaravone by human liver and kidney microsomes: biphasic kinetics and identification of UGT1A9 as the major UDP-glucuronosyltransferase isoform. Drug Metab Dispos 2012; 40: 734−741.
Petri H, de Vet HC, Naus J, et al. Prescription sequence analysis: a new and fast method for assessing certain adverse reactions of prescription drugs in large populations. Stat Med 1988; 7: 1171−1175.
Hallas J. Evidence of depression provoked by cardiovascular medication: a prescription sequence symmetry analysis. Epidemiology 1996; 7: 478−484.
Tsiropoulos I, Andersen M, Hallas J. Adverse events with use of antiepileptic drugs: a prescription and event symmetry analysis. Pharmacoepidemiol Drug Saf 2009; 18: 483−491.
Wahab IA, Pratt NL, Ellett LK, et al. Sequence symmetry analysis as a signal detection tool for potential heart failure adverse events in an administrative claims database. Drug Saf 2016; 39: 347−354.
Pratt N, Andersen M, Bergman U, et al. Multi-country rapid adverse drug event assessment: the Asian Pharmacoepidemiology Network (AsPEN) antipsychotic and acute hyperglycaemia study. Pharmacoepidemiol Drug Saf 2013; 22: 915−924.
Roughead EE, Chan EW, Choi NK, et al. Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis. Expert Opin Drug Saf 2016; 15: 1589−1595.
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Acknowledgements
This study was supported by the China Society for Drug Regulation (CSDR) Project: exploration of criteria for post-marketing risk assessment of medications using real-world data (DRM2021008), and the Special Clinical Pharmacy Program of Shandong Medical Association (YXH2022ZX004). All authors had no conflicts of interest to disclose.
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