DOI QR코드

DOI QR Code

Effectiveness of statin treatment for recurrent stroke according to stroke subtypes

뇌졸중 재발에 대한 스타틴 치료의 뇌졸중 아형에 따른 효과성

  • Min-Surk Kye (Department of Neurology, Seongnam Citizens Medical Center) ;
  • Do Yeon Kim (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Dong-Wan Kang (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Baik Kyun Kim (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Jung Hyun Park (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Hyung Seok Guk (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Nakhoon Kim (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Sang-Won Choi (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Dongje Lee (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Yoona Ko (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Jun Yup Kim (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Jihoon Kang (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Beom Joon Kim (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Moon-Ku Han (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital) ;
  • Hee-Joon Bae (Department of Neurology and Cerebrovascular Center, Seoul National University Bundang Hospital)
  • 계민석 (성남시의료원 신경과) ;
  • 김도연 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 강동완 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 김백균 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 박정현 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 국형석 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 김낙훈 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 최상원 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 이동제 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 고윤아 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 김준엽 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 강지훈 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 김범준 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 한문구 (분당서울대학교병원 신경과 및 뇌혈관센터) ;
  • 배희준 (분당서울대학교병원 신경과 및 뇌혈관센터)
  • Received : 2024.02.26
  • Accepted : 2024.03.13
  • Published : 2024.05.31

Abstract

Understanding the effectiveness of statin treatment is essential for developing tailored stroke prevention strategies. We aimed to evaluate the efficacy of statin treatment in preventing recurrent stroke among patients with various ischemic stroke subtypes. Using data from the Clinical Research Collaboration for Stroke-Korea-National Institute for Health (CRCS-K-NIH) registry, we included patients with acute ischemic stroke admitted between January 2011 and July 2020. To evaluate the differential effects of statin treatment based on the ischemic stroke subtype, we analyzed patients with large artery atherosclerosis (LAA), cardio-embolism (CE), and small vessel occlusion (SVO). The primary outcomes were recurrent ischemic stroke and recurrent stroke events. The hazard ratio for outcomes between statin users and nonusers was compared using a Cox proportional hazards model adjusted for covariates. A total of 46,630 patients who met the inclusion criteria were analyzed. Statins were prescribed to 92%, 93%, and 78% of patients with LAA, SVO, and CE subtypes, respectively. The hazards of recurrent ischemic stroke and recurrent stroke in statin users were reduced to 0.79 (95% confidence interval [CI], 0.63-0.99) and 0.77 (95% CI, 0.62-0.95) in the LAA subtype and 0.63 (95% CI, 0.52-0.76) and 0.63 (95% CI, 0.53-0.75) in CE subtype compared to nonusers. However, the hazards of these outcomes did not significantly decrease in the SVO subtype. The effectiveness of statin treatment in reducing the risk of recurrent stroke in patients with LAA and CE subtypes has been suggested. Nonetheless, no significant effect was observed in the SVO subtype, suggesting a differential effect of statins on different stroke subtypes.

Keywords

Acknowledgement

This research was supported by a fund (2023-ER1006-00) by Research of Korea Centers for Disease Control and Prevention. We are grateful to the institutions that afforded us the chance to utilize the Clinical Research Collaboration for Stroke in Korea (CRCS-K) databases for our research.

References

  1. Chou R, Cantor A, Dana T, Wagner J, Ahmed AY, Fu R, et al. Statin use for the primary prevention of cardiovascular disease in adults: updated evidence report and systematic review for the US preventive services task force. JAMA 2022;328:754-71. https://doi.org/10.1001/jama.2022.12138
  2. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation 2019;139:e1082-143. https://doi.org/10.1161/CIR.0000000000000624
  3. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88. https://doi.org/10.1093/eurheartj/ehz455
  4. Diamantis E, Kyriakos G, Quiles-Sanchez LV, Farmaki P, Troupis T. The anti-inflammatory effects of statins on coronary artery disease: an updated review of the literature. Curr Cardiol Rev 2017;13:209-16. https://doi.org/10.2174/1573403X13666170426104611
  5. Violi F, Calvieri C, Ferro D, Pignatelli P. Statins as antithrombotic drugs. Circulation 2013;127:251-7. https://doi.org/10.1161/CIRCULATIONAHA.112.145334
  6. Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549-59. https://doi.org/10.1056/NEJMoa061894
  7. Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Bejot Y, et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med 2020;382:9.
  8. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;50:e344-418. https://doi.org/10.1161/STR.0000000000000211
  9. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 1993;24:35-41. https://doi.org/10.1161/01.STR.24.1.35
  10. Mac Grory B, Yaghi S, Cordonnier C, Sposato LA, Romano JG, Chaturvedi S. Advances in recurrent stroke prevention: focus on antithrombotic therapies. Circ Res 2022;130:1075-94. https://doi.org/10.1161/CIRCRESAHA.121.319947
  11. Amarenco P, Benavente O, Goldstein LB, Callahan A 3rd, Sillesen H, Hennerici MG, et al. Results of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) trial by stroke subtypes. Stroke 2009;40:1405-9. https://doi.org/10.1161/STROKEAHA.108.534107
  12. Grau AJ, Weimar C, Buggle F, Heinrich A, Goertler M, Neumaier S, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke 2001;32:2559-66. https://doi.org/10.1161/hs1101.098524
  13. Toni D, Di Angelantonio E, Di Mascio MT, Vinisko R, Bath PM; PRoFESS Study Group. Types of stroke recurrence in patients with ischemic stroke: a substudy from the PRoFESS trial. Int J Stroke 2014;9:873-8. https://doi.org/10.1111/ijs.12150
  14. Shin DH, Lee PH, Bang OY. Mechanisms of recurrence in subtypes of ischemic stroke: a hospital-based follow-up study. Arch Neurol 2005;62:1232-7. https://doi.org/10.1001/archneur.62.8.1232
  15. Yoon Y, Lee DH, Kang DW, Kwon SU, Suh DC, Bang OY, et al. Stroke recurrence patterns are predicted by the subtypes and mechanisms of the past, non-cardiogenic stroke. Eur J Neurol 2013;20:928-34. https://doi.org/10.1111/ene.12101
  16. Bae HJ; CRCS-K Investigators. David G. Sherman lecture award: 15-year experience of the nationwide multicenter stroke registry in Korea. Stroke 2022;53:2976-87. https://doi.org/10.1161/STROKEAHA.122.039212
  17. Ko Y, Lee S, Chung JW, Han MK, Park JM, Kang K, et al. MRI-based algorithm for acute ischemic stroke subtype classification. J Stroke 2014;16:161-72. https://doi.org/10.5853/jos.2014.16.3.161
  18. Martinez-Sanchez P, Rivera-Ordonez C, Fuentes B, Ortega-Casarrubios MA, Idrovo L, Diez-Tejedor E. The beneficial effect of statins treatment by stroke subtype. Eur J Neurol 2009;16:127-33. https://doi.org/10.1111/j.1468-1331.2008.02370.x
  19. Smith EE, Saver JL, Alexander DN, Furie KL, Hopkins LN, Katzan IL, et al. Clinical performance measures for adults hospitalized with acute ischemic stroke: performance measures for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014;45:3472-98. https://doi.org/10.1161/STR.0000000000000045
  20. Kim BJ, Lee SH, Ryu WS, Kang BS, Kim CK, Yoon BW. Low level of low-density lipoprotein cholesterol increases hemorrhagic transformation in large artery atherothrombosis but not in cardioembolism. Stroke 2009;40:1627-32. https://doi.org/10.1161/STROKEAHA.108.539643
  21. Sexton T, Wallace EL, Smyth SS. Anti-thrombotic effects of statins in acute coronary syndromes: at the intersection of thrombosis, inflammation, and platelet-leukocyte interactions. Curr Cardiol Rev 2016;12:324-9. https://doi.org/10.2174/1573403X12666160504100312
  22. Park HK, Lee JS, Hong KS, Cho YJ, Park JM, Kang K, et al. Statin therapy in acute cardioembolic stroke with no guidance-based indication. Neurology 2020;94:e1984-95. https://doi.org/10.1212/WNL.0000000000009397
  23. Ntaios G, Papavasileiou V, Makaritsis K, Milionis H, Manios E, Michel P, et al. Statin treatment is associated with improved prognosis in patients with AF-related stroke. Int J Cardiol 2014;177:129-33. https://doi.org/10.1016/j.ijcard.2014.09.031
  24. Go AS, Lee WY, Yang J, Lo JC, Gurwitz JH. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA 2006;296:2105-11. https://doi.org/10.1001/jama.296.17.2105
  25. Batta A, Hatwal J, Batta A, Verma S, Sharma YP. Atrial fibrillation and coronary artery disease: an integrative review focusing on therapeutic implications of this relationship. World J Cardiol 2023;15:229-43.
  26. Heo J, Lee H, Lee IH, Lim IH, Hong SH, Shin J, et al. Combined use of anticoagulant and antiplatelet on outcome after stroke in patients with nonvalvular atrial fibrillation and systemic atherosclerosis. Sci Rep 2024;14:304.
  27. Hosomi N, Kitagawa K, Nagai Y, Nakagawa Y, Aoki S, Nezu T, et al. Different influences of statin treatment in preventing at-risk stroke subtypes: a post hoc analysis of J-STARS. J Atheroscler Thromb 2020;27:449-60. https://doi.org/10.5551/jat.50518
  28. Yaghi S, Raz E, Yang D, Cutting S, Mac Grory B, Elkind MS, et al. Lacunar stroke: mechanisms and therapeutic implications. J Neurol Neurosurg Psychiatry 2021;92:823-30.  https://doi.org/10.1136/jnnp-2021-326308