Study on Statin Treatment in the Very Elderly Ischemic Stroke Patients and Correlation of Statin Utilization and Short-term Prognosis of Stroke and Statin Adverse Effects

Abstract

Abstract:

Objective To investigate statin utilization in elderly stroke patients and correlation between statin treatment and stroke outcomes of short-term. Methods A total of 425 acute ischemic stroke patients who were older than 60 years old were recruited in this study and divided into two groups by age, the very elderly (75 years old and over) and the elderly (60~74 years old). Collect data of baseline information, statin utilization, blood lipid and liver enzymes levels, short-term functional prognosis assessed by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) and statin adverse effects during hospital and follow-up. Logistic regression was used analyzing correlation between statin utilization and short-term stroke prognosis, statin adverse effects in both groups. Results There were no significant differences in statin utilization during hospitalization between two groups. Compared with the elderly group, the very elderly group had a lower statin utilization percent (85.0% vs 91.6%, P=0.039), and a higher rate of poor prognosis (57.6% vs 30.7%, P<0.001) in follow-up. Logistic regression showed that in both groups, regular statin usage showed benefit to short term prognosis (very elderly:odds ratio [OR]=0.619, P<0.05, elderly:OR=0.498, P<0.05); In the very elderly group, regular statin usage was associated with isolated elevation of liver enzymes (OR=1.789, P<0.05). Conclusion The very elderly show poorer statin compliance after discharge and worsened prognosis in the short term compared with the elderly. Regular statin utilization shows benefit to stroke prognosis in all elderly stroke patients, and is related to isolated elevation of liver enzymes in the very elderly stroke patients.

Key words: The very elderly; Ischemic stroke; Statins; Short-term prognosis; Adverse effect

摘要：

目的分析高龄老年缺血性卒中患者他汀药物的使用并与患者短期预后、不良反应的相关性。方法纳入年龄≥60岁急性缺血性卒中患者425例，按年龄分为高龄组（≥75岁）和老龄组（60～74岁）；记录入院期间及卒中后（90±7）d他汀类药物治疗情况，评估患者短期预后［改良Rankin量表（modified Rankin Scale，mRS）］及相关不良反应情况。对他汀药物使用与短期预后及相关不良反应进行相关性分析。结果入院期间两组他汀药物使用无明显差异；卒中后（90±7）d，高龄组他汀药物使用率较老龄组低（85.0% vs 91.6%，P=0.039），高龄组3个月预后不良率（mRS 3～5分）较老龄组比例高（57.6% vs 30.7%，P＜0.001）。Logistic多因素分析显示，无论高龄组还是老龄组，规律使用他汀类药物是卒中后3个月功能预后的保护性因素［比值比（odds ratio，OR）=0.619，P＜0.05；OR=0.498，P＜0.05］；高龄组规律他汀药物与住院期间孤立性肝酶升高相关（OR=1.789，P＜0.05）。结论高龄卒中患者出院后他汀类药物的依从性及3个月功能预后较老龄患者差；高龄和老龄卒中患者规律使用他汀类药物是短期功能预后的保护性因素；高龄患者规律使用他汀药物与孤立性肝酶升高相关。

关键词: 高龄; 缺血性卒中; 他汀; 短期卒中预后; 不良反应

WU Jia, WU Shuo-Lin, LI Jing-Jing, WANG Yan, WANG Chun-Xue.. Study on Statin Treatment in the Very Elderly Ischemic Stroke Patients and Correlation of Statin Utilization and Short-term Prognosis of Stroke and Statin Adverse Effects [J]. Chinese Journal of Stroke, 2015, 10(05): 391-400.

吴佳，吴硕琳，李菁晶，王琰，王春雪. 老年缺血性卒中住院患者他汀药物治疗短期预后及不良反应相关性研究[J]. 中国卒中杂志, 2015, 10(05): 391-400.

References

1 Koton S, Schneider AL, Rosamond WD, et al. Stroke incidence and mortality trends in US communities, 1987 to 2011[J]. JAMA, 2014, 312:259-268.

2 Heuschmann PU, Di Carlo A, Bejot Y, et al. Incidence of stroke in Europe at the beginning of the 21st century[J]. Stroke, 2009, 40:1557-1563.

3 Bejot Y, Rouaud O, Jacquin A, et al. Stroke in the very old:incidence, risk factors, clinical features, outcomes and access to resources--a 22-year population-based study[J]. Cerebrovasc Dis, 2010, 29:111-121.

4 Lee M, Huang WY, Weng HH, et al, First-ever ischemic stroke in very old Asians:clinical features, stroke subtypes, risk factors and outcome[J]. Eur Neurol, 2007, 58:44-48.

5 他汀类药物防治缺血性卒中/短暂性脑缺血发作专家共识组. 他汀类药物防治缺血性卒中/短暂性脑缺血发作专家共识[J]. 中国卒中杂志, 2013, 8:565-575.

6 Ni CD, Asplund K, Asberg S, et al. Statin therapy and outcome after ischemic stroke:systematic review and meta-analysis of observational studies and randomized trials[J]. Stroke, 2013, 44:448-456.

7 Amarenco P, Labreuche J, Lavallee P, et al. Statins in stroke prevention and carotid atherosclerosis:systematic review and up-to-date meta-analysis[J]. Stroke, 2004, 35:2902-2909.

8 中华医学会神经病学分会脑血管病学组急性缺血性脑卒中诊治指南撰写组. 中国急性缺血性脑卒中诊治指南2010[J]. 中华神经科杂志, 2010, 43:146-153.

9 刘力生, 王文, 姚崇华, 中国高血压防治指南(2009年基层版)[J]. 中华高血压杂志, 2010, 18:11-30.

10 中华医学会糖尿病学分会. 中国2型套尿病防治指南(2013年版)[J]. 中华糖尿病杂志, 2014, 6:447-498.

11 中国成人血脂异常防治指南制订联合委员会. 中国成人血脂异常防治指南[J]. 中华心血管病杂志, 2007(05):390-419.

12 Montalescot G, SechtemU, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease:the Task Force on the management of stable coronary artery disease of the European Society of Cardiology[J]. Eur Heart J, 2013, 34:2949-3003.

13 Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation:an update of the 2010 ESC guidelines for the management of atrial fibrillation--developed with the special contribution of the European Heart Rhythm Association[J]. Europace, 2012, 14:1385-1413.

14 Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline):a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines:developed in collaboration with the Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine, and Society for Vascular Surgery[J]. Catheter Cardiovasc Interv, 2012, 79:501-531.

15 Gao S, Wang YJ, Xu AD, et al. Chinese ischemic stroke subclassification[J]. Front Neurol, 2011, 2:6.

16 Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy:a meta-analysis[J]. JAMA, 2011, 305:2556-2564.

17 Paraskevas KI, Mikhailidis DP, Veith FJ. Optimal statin type and dosage for vascular patients[J]. J Vasc Surg, 2011, 53:837-844.

18 Bjornsson E, Jacobsen EI, Kalaitzakis E. Hepatotoxicity associated with statins:reports of idiosyncratic liver injury post-marketing[J]. J Hepatol, 2012, 56:374-380.

19 Aithal GP, Watkins PB, Andrade RJ, et al. Case definition and phenotype standardization in drug-induced liver injury[J]. Clin Pharmacol Ther, 2011, 89:806-815.

20 Rosenson RS, Baker SK, Jacobson TA, et al. An assessment by the Statin Muscle Safety Task Force:2014 update[J]. J Clin Lipidol, 2014, 8(3 Suppl):S58-S71.

21 Thompson PD, Clarkson PM, Rosenson RS. An assessment of statin safety by muscle experts[J]. Am J Cardiol, 2006, 97(8A):69C-76C.

22 Kamouchi M, Matsuki T, Hata J, et al. Prestroke glycemic control is associated with the functional outcome in acute ischemic stroke:the Fukuoka Stroke Registry[J]. Stroke, 2011, 42:2788-2794.

23 Uyttenboogaart M, Stewart RE, Vroomen PC, et al. Optimizing cutoff scores for the Barthel index and the modified Rankin scale for defining outcome in acute stroke trials[J]. Stroke, 2005, 36:1984-1987.

24 Hacke W, Albers G, Al-Rawi Y, et al. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS):a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase[J]. Stroke, 2005, 36:66-73.

25 Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990-2010:findings from the Global Burden of Disease Study 2010[J]. Lancet, 2013, 381:1987-2015.

26 Wu X, Zhu B, Fu L, et al. Prevalence, incidence, and mortality of stroke in the Chinese island populations:a systematic review[J]. PLoS One, 2013, 8:e78629.

27 Amarenco P, Bogousslavsky J, Callahan AR, et al. High-dose atorvastatin after stroke or transient ischemic attack[J]. N Engl J Med, 2006, 355:549-559.

28 O'Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study):a case-control study[J]. Lancet, 2010, 376:112-123.

29 Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment:prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins[J]. Lancet, 2005, 366:1267-1278.

30 Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack:a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2011, 42:227-276.

31 Ovbiagele B, Saver JL, Bang H, et al. Statin treatment and adherence to national cholesterol guidelines after ischemic stroke[J]. Neurology, 2006, 66:1164-1170.

32 Cohen DE, Anania FA, Chalasani N. An assessment of statin safety by hepatologists[J]. Am J Cardiol, 2006, 97(8A):77C-81C.

33 Mukai M, Ozasa K, Hayashi K, et al. Various S-GOT/S-GPT ratios in nonviral liver disorders and related physical conditions and life-style[J]. Dig Dis Sci, 2002, 47:549-555.

34 范建高. 中国非酒精性脂肪性肝病诊疗指南(2010年修订版)[J]. 中国医学前沿杂志(电子版), 2012(07):4-10.

35 Paquet M, Pilon D, Tetrault JP, et al. Protective vascular treatment of patients with peripheral arterial disease:guideline adherence according to year, age and gender[J]. Can J Public Health, 2010, 101:96-100.

36 Castberg I, Westin AA, Spigset O. Does level of care, sex, age, or choice of drug influence adherence to treatment with antipsychotics?[J] J Clin Psychopharmacol, 2009, 29:415-420.

37 De Schryver EL, van Gijn J, Kappelle LJ, et al. Non-adherence to aspirin or oral anticoagulants in secondary prevention after ischaemic stroke[J]. J Neurol, 2005, 252:1316-1321.

38 Weimar C, Ziegler A, Konig IR, et al. Predicting functional outcome and survival after acute ischemic stroke[J]. J Neurol, 2002, 249:888-895.

39 Heuschmann PU, Kolominsky-Rabas PL, Misselwitz B, et al. Predictors of in-hospital mortality and attributable risks of death after ischemic stroke:the German Stroke Registers Study Group[J]. Arch Intern Med, 2004, 164:1761-1768.

[1]	CAO Liming, REN Lijie. Progress and Prospects of Diagnosis and Treatment Techniques for Acute Ischemic Stroke [J]. Chinese Journal of Stroke, 2024, 19(9): 983-989.
[2]	FU Pengcheng, CAO Liming, ZHU Jiaqian, ZHAO Guiyu, XU Gelin. Research Progress of Reperfusion Therapy for Large Artery Atherosclerotic Ischemic Stroke [J]. Chinese Journal of Stroke, 2024, 19(9): 1004-1011.
[3]	ZHANG Liping, CAO Liming, XIAO Nan, LIAO Yuqi, CHI Feng, YU Yanni, REN Lijie. Research Progress and Challenges of Nanomaterials in the Diagnosis and Treatment of Ischemic Stroke [J]. Chinese Journal of Stroke, 2024, 19(9): 1012-1017.
[4]	WANG Xiaorui, LUO Song, ZOU Liangyu, QU Hongdang, CUI Xue, ZHAO Yujie. Value of Eosinophil-to-Monocyte Ratio in Predicting the Prognosis of Patients with Acute Ischemic Stroke Receiving Intravenous Thrombolysis [J]. Chinese Journal of Stroke, 2024, 19(9): 1025-1033.
[5]	WANG Shuo, YU Ping, ZHANG Ning, WANG Chunxue. Bibliometric Analysis of References on the Correlation between Ischemic Stroke and Sleep from 2013 to 2023 [J]. Chinese Journal of Stroke, 2024, 19(9): 1040-1047.
[6]	ZHOU Hongyu, LI Zixiao, WANG Yongjun. Research Progress on Radiomics-Based Brain Age Prediction and Ischemic Stroke [J]. Chinese Journal of Stroke, 2024, 19(9): 1066-1076.
[7]	ABULANIYAZI Anaguli, WU Xiaoxin, LI Jiaoxing, LI Zhuhao, SHENG Wenli. Research Progress on Factors Related to the Susceptibility Vessel Sign and its Clinical Application in Acute Ischemic Stroke [J]. Chinese Journal of Stroke, 2024, 19(9): 1077-1085.
[8]	WU Chunyan, YIN Yashi, WANG Guangzhi, YUE Kuitao. Evaluation and Application of Medical Imaging for Acute Ischemic Stroke at Different Time Windows: A Review [J]. Chinese Journal of Stroke, 2024, 19(9): 1094-1101.
[9]	ZHANG Mengruo, XU Shouchen, SUI Cuicui, LI Yukui, WANG Xueli. The Effects of Lower Limb Rehabilitation Robot Combined with Scalp Acupuncture on the Walking Efficiency and Coordination Function in Elderly Patients with Ischemic Stroke [J]. Chinese Journal of Stroke, 2024, 19(8): 902-908.
[10]	WU Yuqian, ZHANG Yumei, ZANG Dawei, FAN Xiaowei, WANG Anxin, ZHANG Xiaoli, MENG Xia. Study on the Reliability, Validity, and Sensitivity of Action Research Arm Test Scale in Evaluating the Function of Hemiplegic Upper Limb and Hand in Subacute Stage Ischemic Stroke Patients [J]. Chinese Journal of Stroke, 2024, 19(8): 915-923.
[11]	MO Qiuhong, DING Xiaobo, LI Jing, ZHANG Yanbo, LI Weirong. Research on Prediction of Recurrence of Minor Ischemic Stroke Based on Interpretable Machine Learning Models [J]. Chinese Journal of Stroke, 2024, 19(8): 924-930.
[12]	LU Dan, CHEN Weiqi, WANG Yaping, DUAN Wanying, GUO Lei, WANG Ling, LIU Liping, XU Anding, WANG Yongjun, Cerebroprotection Academic Roundtable Academic Committee of Chinese Stroke Association . Scientific Statements on Brain Cytoprotection in Ischemic Stroke—A Scientific Statement from the Chinese Stroke Association [J]. Chinese Journal of Stroke, 2024, 19(8): 938-955.
[13]	LI Guangshuo, ZHAO Xingquan. Interpretation of the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023 [J]. Chinese Journal of Stroke, 2024, 19(8): 956-961.
[14]	BAI Leipeng, LUO Jie, ZHOU Sijie, HUANG Jianhui, LIANG Mingqin, ZHAO Qingshun. Interventional Thrombectomy in Patients with Acute Ischemic Stroke after Wedge Resection of Pulmonary Lobes: Two Case Reports and Literature Review [J]. Chinese Journal of Stroke, 2024, 19(8): 962-966.
[15]	ZHAO Yan, YAO Jingxin, PENG Yuming. A Report of Simultaneous Complications of Ischemic Stroke and Intracerebral Hemorrhage in Geriatric Patients Undergoing Craniotomy for Tumor Resections during the Perioperative Period [J]. Chinese Journal of Stroke, 2024, 19(7): 797-802.