Effect of high-dose strong statin for preventing periprocedural ischemic complications of carotid artery stenting

  • Norihiko ShinozakiEmail author
  • Tsutomu Murakami
  • Yohei Ohno
  • Masataka Nakano
  • Toshiharu Fujii
  • Gaku Nakazawa
  • Fuminobu Yoshimachi
  • Yuji Ikari
Original Article


Statin therapy has been shown to induce carotid atherosclerotic plaque regression and reduce the periprocedural ischemic complications of carotid artery stenting (CAS). This study assessed the safety and usefulness of pretreatment using a high-dose strong statin (HDSS) to reduce the periprocedural ischemic complications of CAS. We analyzed 117 carotid lesions treated by CAS that were evaluated with magnetic resonance imaging (MRI) within 48 h after the procedure. For 67 lesions, an HDSS (rosuvastatin 20 mg or atorvastatin 40 mg daily) were prescribed from at least 14 days before CAS to at least 14 days after procedure (HDSS group). Clinical and angiographic data, as well as in-hospital outcomes, of the HDSS group were retrospectively compared with 50 lesions with conventional treatment without an HDSS (non-HDSS group). There were no significant differences in the baseline clinical and procedural characteristics between the two groups. There was no side effect related to the HDSS. Stroke rates were similar between the two groups (3.0% in HDSS group vs 8.0% in non-HDSS group, p = 0.22). All were minor strokes. Compared to the non-HDSS group, the HDSS group had a lower frequency of new lesions on diffusion-weighted imaging (DWI) with MRI (25.4% vs 44.0%, p = 0.0345). New ipsilateral DWI-positive rate in the HDSS group was significantly lower than in the non-HDSS group (16.4% vs 34.0%, p = 0.0275). Nonipsilateral (contralateral or posterior circulation) DWI-positive rates were similar between the two groups (13.4% vs 20.0%, p = 0.34). Pretreatment with an HDSS might reduce the periprocedural ischemic complications of CAS.


Carotid artery stenosis Carotid artery stenting Strong statin Ischemic complication Magnetic resonance imaging Diffusion-weighted imaging 



Carotid artery stenting


Carotid endarterectomy


High-dose strong statin


Magnetic resonance imaging


Diffusion-weighted imaging


Compliance with ethical standards

Conflict of interest



  1. 1.
    Barnett HJM, Taylor DW, Haynes RB, Sackett DL, Peerless SJ, Ferguson GG, Fox AJ, Rankin RN, Hachinski VC, Wiebers DO, Eliasziw M, North American Symptomatic Carotid Endarterectomy Trial C (1991) Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 325(7):445–453CrossRefGoogle Scholar
  2. 2.
    Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, Rankin RN, Clagett GP, Hachinski VC, Sackett DL, Thorpe KE, Meldrum HE, Spence JD (1998) Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 339(20):1415–1425CrossRefGoogle Scholar
  3. 3.
    Walker MD, Marler JR, Goldstein M, Grady PA, Toole JF, Baker WH, Castaldo JE, Chambless LE, Moore WS, Robertson JT, Young B, Howard VJ, Purvis S, Vernon DD, Needham K, Beck P, Celani VJ, Sauerbeck L, von Rajcs JA, Atkins D (1995) Endarterectomy for asymptomatic carotid artery stenosis. Executive committee for the asymptomatic carotid atherosclerosis study. JAMA 273(18):1421–1428CrossRefGoogle Scholar
  4. 4.
    Yadav JS, Wholey MH, Kuntz RE, Fayad P, Katzen BT, Mishkel GJ, Bajwa TK, Whitlow P, Strickman NE, Jaff MR, Popma JJ, Snead DB, Cutlip DE, Firth BG, Ouriel K, Stenting, Angioplasty with Protection in Patients at High Risk for Endarterectomy I (2004) Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 351(15):1493–1501CrossRefGoogle Scholar
  5. 5.
    Brott TG, Hobson RW 2nd, Howard G, Roubin GS, Clark WM, Brooks W, Mackey A, Hill MD, Leimgruber PP, Sheffet AJ, Howard VJ, Moore WS, Voeks JH, Hopkins LN, Cutlip DE, Cohen DJ, Popma JJ, Ferguson RD, Cohen SN, Blackshear JL, Silver FL, Mohr JP, Lal BK, Meschia JF, Investigators C (2010) Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 363(1):11–23CrossRefGoogle Scholar
  6. 6.
    Yamada K, Yoshimura S, Kawasaki M, Enomoto Y, Asano T, Hara A, Minatoguchi S, Iwama T (2011) Embolic complications after carotid artery stenting or carotid endarterectomy are associated with tissue characteristics of carotid plaques evaluated by magnetic resonance imaging. Atherosclerosis 215(2):399–404CrossRefGoogle Scholar
  7. 7.
    Zhao XQ, Dong L, Hatsukami T, Phan BA, Chu B, Moore A, Lane T, Neradilek MB, Polissar N, Monick D, Lee C, Underhill H, Yuan C (2011) MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course. JACC Cardiovasc Imaging 4(9):977–986CrossRefGoogle Scholar
  8. 8.
    Du R, Cai J, Zhao XQ, Wang QJ, Liu DQ, Leng WX, Gao P, Wu HM, Ma L, Ye P (2014) Early decrease in carotid plaque lipid content as assessed by magnetic resonance imaging during treatment of rosuvastatin. BMC Cardiovasc Disord 14:83CrossRefGoogle Scholar
  9. 9.
    Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J (2019) 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 139(25):e1046–e1081PubMedGoogle Scholar
  10. 10.
    Shinozaki N, Ogata N, Ikari Y (2014) Plaque protrusion detected by intravascular ultrasound during carotid artery stenting. J Stroke Cerebrovasc Dis 23(10):2622–2625CrossRefGoogle Scholar
  11. 11.
    Ansel GM, Hopkins LN, Jaff MR, Rubino P, Bacharach JM, Scheinert D, Myla S, Das T, Cremonesi A (2010) Safety and effectiveness of the INVATEC MO.MA proximal cerebral protection device during carotid artery stenting: results from the ARMOUR pivotal trial. Catheter Cardiovasc Interv 76(1):1–8CrossRefGoogle Scholar
  12. 12.
    Montorsi P, Caputi L, Galli S, Ciceri E, Ballerini G, Agrifoglio M, Ravagnani P, Trabattoni D, Pontone G, Fabbiocchi F, Loaldi A, Parati E, Andreini D, Veglia F, Bartorelli AL (2011) Microembolization during carotid artery stenting in patients with high-risk, lipid-rich plaque A randomized trial of proximal versus distal cerebral protection. J Am Coll Cardiol 58(16):1656–1663CrossRefGoogle Scholar
  13. 13.
    Bijuklic K, Wandler A, Hazizi F, Schofer J (2012) The PROFI study (prevention of cerebral embolization by proximal balloon occlusion compared to filter protection during carotid artery stenting): a prospective randomized trial. J Am Coll Cardiol 59(15):1383–1389CrossRefGoogle Scholar
  14. 14.
    Texakalidis P, Letsos A, Kokkinidis DG, Schizas D, Karaolanis G, Giannopoulos S, Economopoulos KP, Bakoyannis C (2018) Proximal embolic protection versus distal filter protection versus combined protection in carotid artery stenting: a systematic review and meta-analysis. Cardiovasc Revasc Med 19(5 Pt A):545–552CrossRefGoogle Scholar
  15. 15.
    Okazaki S, Yokoyama T, Miyauchi K, Shimada K, Kurata T, Sato H, Daida H (2004) Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study. Circulation 110(9):1061–1068CrossRefGoogle Scholar
  16. 16.
    Takayama T, Hiro T, Yamagishi M, Daida H, Hirayama A, Saito S, Yamaguchi T, Matsuzaki M, Investigators C (2009) Effect of rosuvastatin on coronary atheroma in stable coronary artery disease: multicenter coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS). Circ J 73(11):2110–2117CrossRefGoogle Scholar
  17. 17.
    Hirayama A, Saito S, Ueda Y, Takayama T, Honye J, Komatsu S, Yamaguchi O, Li Y, Yajima J, Nanto S, Takazawa K, Kodama K (2009) Qualitative and quantitative changes in coronary plaque associated with atorvastatin therapy. Circ J 73(4):718–725CrossRefGoogle Scholar
  18. 18.
    Takayama T, Komatsu S, Ueda Y, Fukushima S, Hiro T, Hirayama A, Saito S, group As (2016) Comparison of the effect of Rosuvastatin 2.5 mg vs 20 mg on Coronary Plaque determined by angioscopy and intravascular ultrasound in Japanese with stable angina pectoris (from the aggressive lipid-lowering treatment approach using intensive rosuvastatin for vulnerable coronary artery plaque [ALTAIR] randomized trial). Am J Cardiol 117(8), 1206–1212.Google Scholar
  19. 19.
    Takano H, Ohba T, Yamamoto E, Miyachi H, Inui K, Kawanaka H, Kamiya M, Kikuchi A, Takahashi Y, Tanabe J, Inami S, Takagi G, Asai K, Yasutake M, Ibuki C, Tanaka K, Kusama Y, Seino Y, Munakata K, Mizuno K, Investigators PS (2013) Usefulness of rosuvastatin to prevent periprocedural myocardial injury in patients undergoing elective coronary intervention. Am J Cardiol 111(12):1688–1693CrossRefGoogle Scholar
  20. 20.
    Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T, Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Study I (2001) Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 285(13):1711–1718CrossRefGoogle Scholar
  21. 21.
    Dohi T, Miyauchi K, Okazaki S, Yokoyama T, Yanagisawa N, Tamura H, Kojima T, Yokoyama K, Kurata T, Daida H (2010) Early intensive statin treatment for six months improves long-term clinical outcomes in patients with acute coronary syndrome (Extended-ESTABLISH trial): a follow-up study. Atherosclerosis 210(2):497–502CrossRefGoogle Scholar
  22. 22.
    Yun KH, Oh SK, Rhee SJ, Yoo NJ, Kim NH, Jeong JW (2011) 12-month follow-up results of high dose rosuvastatin loading before percutaneous coronary intervention in patients with acute coronary syndrome. Int J Cardiol 146(1):68–72CrossRefGoogle Scholar
  23. 23.
    Yun KH, Jeong MH, Oh SK, Rhee SJ, Park EM, Lee EM, Yoo NJ, Kim NH, Ahn YK, Jeong JW (2009) The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients with acute coronary syndrome. Int J Cardiol 137(3):246–251CrossRefGoogle Scholar
  24. 24.
    Wang Z, Dai H, Xing M, Yu Z, Lin X, Wang S, Zhang J, Hou F, Ma Y, Ren Y, Tan K, Wang Y, Ge Z (2013) Effect of a single high loading dose of rosuvastatin on percutaneous coronary intervention for acute coronary syndromes. J Cardiovasc Pharmacol Ther 18(4):327–333CrossRefGoogle Scholar
  25. 25.
    Tsujita K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K, Komura N, Sakamoto K, Oka H, Nakao K, Nakamura S, Ishihara M, Matsui K, Sakaino N, Nakamura N, Yamamoto N, Koide S, Matsumura T, Fujimoto K, Tsunoda R, Morikami Y, Matsuyama K, Oshima S, Kaikita K, Hokimoto S, Ogawa H (2015) Impact of dual lipid-lowering strategy with ezetimibe and atorvastatin on coronary plaque regression in patients with percutaneous coronary intervention: the multicenter randomized controlled PRECISE-IVUS trial. J Am Coll Cardiol 66(5):495–507CrossRefGoogle Scholar
  26. 26.
    Takayama K, Taki W, Toma N, Nakahara I, Maeda M, Tanemura H, Kuroiwa T, Imai K, Sakamoto M, Nakagawa I, Masuo O, Myouchin K, Wada T, Suzuki H (2014) Effect of pitavastatin on preventing ischemic complications with carotid artery stenting: a multicenter prospective study–EPOCH-CAS study. Cardiovasc Intervent Radiol 37(6):1436–1443CrossRefGoogle Scholar
  27. 27.
    Verzini F, De Rango P, Parlani G, Giordano G, Caso V, Cieri E, Isernia G, Cao P (2011) Effects of statins on early and late results of carotid stenting. J Vasc Surg 53(1):71–79; discussion 79CrossRefGoogle Scholar
  28. 28.
    Patti G, Tomai F, Melfi R, Ricottini E, Macri M, Sedati P, Giardina A, Aurigemma C, Leporace M, D'Ambrosio A, Di Sciascio G (2013) Strategies of clopidogrel load and atorvastatin reload to prevent ischemic cerebral events in patients undergoing protected carotid stenting. Results of the randomized ARMYDA-9 CAROTID (clopidogrel and atorvastatin treatment during carotid artery stenting) study. J Am Coll Cardiol 61(13):1379–1387CrossRefGoogle Scholar
  29. 29.
    Reiff T, Amiri H, Rohde S, Hacke W, Ringleb PA (2014) Statins reduce peri-procedural complications in carotid stenting. Eur J Vasc Endovasc Surg 48(6):626–632CrossRefGoogle Scholar
  30. 30.
    Hong JH, Sohn SI, Kwak J, Yoo J, Chang HW, Kwon OK, Jung C, Chung I, Bae HJ, Lee JS, Han MK (2017) Dose-dependent effect of statin pretreatment on preventing the periprocedural complications of carotid artery stenting. Stroke 48(7):1890–1894CrossRefGoogle Scholar
  31. 31.
    Gensicke H, van der Worp HB, Nederkoorn PJ, Macdonald S, Gaines PA, van der Lugt A, Mali WP, Lyrer PA, Peters N, Featherstone RL, de Borst GJ, Engelter ST, Brown MM, Bonati LH, Investigators I-MS (2015) Ischemic brain lesions after carotid artery stenting increase future cerebrovascular risk. J Am Coll Cardiol 65(6):521–529CrossRefGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2020

Authors and Affiliations

  • Norihiko Shinozaki
    • 1
    Email author
  • Tsutomu Murakami
    • 1
  • Yohei Ohno
    • 1
  • Masataka Nakano
    • 1
  • Toshiharu Fujii
    • 1
  • Gaku Nakazawa
    • 1
  • Fuminobu Yoshimachi
    • 1
  • Yuji Ikari
    • 1
  1. 1.Department of CardiologyTokai University School of MedicineIseharaJapan

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