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Perspective

What are the benefits and drawbacks of statins in carotid artery disease? A perspective review

ORCID Icon, ORCID Icon &
Pages 763-777 | Received 15 Sep 2023, Accepted 16 Nov 2023, Published online: 23 Nov 2023

References

  • Song P, Fang Z, Wang H, et al. Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study. Lancet Glob Health. 2020 May;8(5):e721–e729. doi: 10.1016/S2214-109X(20)30117-0
  • van Velzen TJ, Kuhrij LS, Westendorp WF, et al. Prevalence, predictors and outcome of carotid stenosis: a sub study in the preventive antibiotics in stroke study (PASS). BMC neurol. 2021 Jan 12;21(1):20. doi: 10.1186/s12883-020-02032-4
  • Kamtchum-Tatuene J, Noubiap JJ, Wilman AH, et al. Prevalence of high-risk plaques and risk of stroke in patients with asymptomatic carotid stenosis: a meta-analysis. JAMA Neurol. 2020 Dec 1;77(12):1524–1535. doi: 10.1001/jamaneurol.2020.2658
  • de Weerd M, Greving JP, Hedblad B, et al. Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis. Stroke. 2010 Jun;41(6):1294–1297. doi: 10.1161/STROKEAHA.110.581058
  • Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2023 update: a report from the American Heart association. Circulation. 2023 Feb 21;147(8):e93–e621. doi: 10.1161/CIR.0000000000001123
  • Gortler D, Maloney S, Rutland R, et al. Adjunctive pharmacologic use in carotid endarterectomy: a review. Vascular. 2006 Mar;14(2):93–102. doi: 10.2310/6670.2006.00020
  • Paraskevas KI, Gloviczki P, Antignani PL, et al. Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease. Prog Cardiovasc Dis. 2022 Jul;73:41–47.
  • Amarenco P, Labreuche J, Lavallée P, et al. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke. 2004 Dec;35(12):2902–2909. doi: 10.1161/01.STR.0000147965.52712.fa
  • Naylor R, Rantner B, Ancetti S, et al. Editor’s choice - European Society for Vascular Surgery (ESVS) 2023 clinical practice guidelines on the management of atherosclerotic carotid and vertebral artery disease. Eur J Vasc Endovasc Surg. 2023 Jan;65(1):7–111. doi: 10.1016/j.ejvs.2022.04.011
  • Arnett DK, Blumenthal RS, Albert MA, et al. ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart association Task Force on clinical practice guidelines. Circulation. 2019;140(11):e596–e646.
  • Merwick Á, Albers GW, Arsava EM, et al. Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment. Stroke. 2013 Oct;44(10):2814–2820. doi: 10.1161/STROKEAHA.113.001576
  • Poldermans D, Bax JJ, Kertai MD, et al. Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery. Circulation. 2003 Apr 15;107(14):1848–1851. doi: 10.1161/01.CIR.0000066286.15621.98
  • Anjorin AC, Marcaccio CL, Rastogi V, et al. Statin therapy is associated with improved perioperative outcomes and long-term mortality following carotid revascularization in the Vascular quality initiative. J Vasc Surg. 2023 Jan;77(1):158–169.e8. doi: 10.1016/j.jvs.2022.08.019
  • World Health Organization. Cardiovascular diseases: avoiding heart attacks and strokes cited 2023 Jul 5 . Available from: https://www.who.int/news-room/questions-and-answers/item/cardiovascular-diseases-avoiding-heart-attacks-and-strokes
  • Centers for Disease Control and Prevention. Preventing Stroke Deaths Cited 2023jul 5 Available from: https://www.cdc.gov/vitalsigns/stroke/index.html
  • Bir SC, Kelley RE. Carotid atherosclerotic disease: a systematic review of pathogenesis and management. Brain Circ. 2022 Jul;8(3):127–136. doi: 10.4103/bc.bc_36_22
  • Garcia JH, Khang-Loon H. Carotid atherosclerosis. Definition, pathogenesis, and clinical significance. Neuro Clinical N Am. 1996 Nov;6(4):801–810.
  • Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Statins: pros and cons. Med Clin. 2018 May 23;150(10):398–402. doi: 10.1016/j.medcli.2017.11.030
  • Sizar O, Khare S, Jamil RT, et al. Statin medications. Treasure Island, FL: StatPearls Publishing; 2023. https://www.ncbi.nlm.nih.gov/books/NBK430940/
  • Ward NC, Watts GF, Eckel RH. Statin toxicity. Circ Res. 2019 Jan 18;124(2):328–350. doi: 10.1161/CIRCRESAHA.118.312782
  • Wasserman BA. Clinical carotid atherosclerosis. Neuro Clinical N Am. 2002 Aug;12(3):403–419. doi: 10.1016/S1052-5149(02)00025-4
  • Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers. 2019 Aug 16;5(1):56. doi: 10.1038/s41572-019-0106-z
  • Bentzon JF, Otsuka F, Virmani R, et al. Mechanisms of Plaque Formation and Rupture. Circ Res. 2014;114(12):1852–1866. doi: 10.1161/CIRCRESAHA.114.302721
  • Paraskevas KI, Veith FJ, Eckstein H-H, et al. Cholesterol, carotid artery disease and stroke: what the vascular specialist needs to know. Ann translat Med. 2020;8(19):1265. doi: 10.21037/atm.2020.02.176
  • Ovbiagele B, Nguyen-Huynh MN. Stroke epidemiology: advancing our understanding of disease mechanism and therapy. Neurotherapeutics. 2011 Jul;8(3):319–329. doi: 10.1007/s13311-011-0053-1
  • Kapila V, Jetty P, Basile VS, et al. Management of transient ischemic attack or nondisabling stroke related to extracranial internal carotid artery stenosis. CMAJ. 2019 Apr 15;191(15):E418–e422. doi: 10.1503/cmaj.180735
  • Woo SY, Joh JH, Han SA, et al. Prevalence and risk factors for atherosclerotic carotid stenosis and plaque: a population-based screening study. Medicine (Baltimore). 2017 Jan;96(4):e5999. doi: 10.1097/MD.0000000000005999
  • Gong H-Y, Shi X-K, Zhu H-Q, et al. Evaluation of carotid atherosclerosis and related risk factors using ultrasonic B-Flow technology in elderly patients. J Int Med Res. 2020;48(10):0300060520961224. doi: 10.1177/0300060520961224
  • Chien KL, Liau CS, Chen MF, et al. Primary hypercholesterolemia, carotid atherosclerosis and insulin resistance among Chinese. Lipids. 2008 Feb;43(2):117–124. doi: 10.1007/s11745-007-3138-1
  • Ershova AI, Meshkov AN, Rozhkova TA, et al. Carotid and aortic stiffness in patients with heterozygous familial hypercholesterolemia. PLoS One. 2016;11(7):e0158964. doi: 10.1371/journal.pone.0158964
  • Zhang Q, Liu S, Liu Y, et al. Achieving low density lipoprotein-cholesterol<70mg/dL may be associated with a trend of reduced progression of carotid artery atherosclerosis in ischemic stroke patients. J Neurol Sci. 2017 Jul 15;378:26–29. doi: 10.1016/j.jns.2017.04.024
  • Ku DN, Giddens DP, Zarins CK, et al. Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis. 1985 May;5(3):293–302. doi: 10.1161/01.ATV.5.3.293
  • Zarins CK, Giddens DP, Bharadvaj BK, et al. Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res. 1983 Oct;53(4):502–514. doi: 10.1161/01.RES.53.4.502
  • Box FM, van der Grond J, de Craen AJ, et al. Pravastatin decreases wall shear stress and blood velocity in the internal carotid artery without affecting flow volume: results from the PROSPER MRI study. Stroke. 2007 Apr;38(4):1374–1376. doi: 10.1161/01.STR.0000260206.56774.aa
  • Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med. 2001 Oct;5(4):378–387. doi: 10.1111/j.1582-4934.2001.tb00172.x
  • Crisby M, Nordin-Fredriksson G, Shah PK, et al. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation. 2001 Feb 20;103(7):926–933. doi: 10.1161/01.CIR.103.7.926
  • Lioutas V-A, Ivan CS, Himali JJ, et al. Incidence of transient ischemic attack and association with long-term risk of stroke. JAMA. 2021;325(4):373–381. doi: 10.1001/jama.2020.25071
  • Naylor AR, Ricco JB, de Borst GJ, et al. Editor’s choice - management of atherosclerotic carotid and vertebral artery disease: 2017 clinical practice guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018 Jan;55(1):3–81. doi: 10.1016/j.ejvs.2017.06.021
  • Disease C, Prevention C. About stroke, stroke statistics and facts [cited2023 jun]. https://www.cdc.gov/stroke/about.htm
  • Dijk JM, van der Graaf Y, Grobbee DE, et al. Carotid stiffness indicates risk of ischemic stroke and TIA in patients with internal carotid artery stenosis: the SMART study. Stroke. 2004 Oct;35(10):2258–2262. doi: 10.1161/01.STR.0000141702.26898.e9
  • Paraskevas KI, Hamilton G, Mikhailidis DP. Statins: an essential component in the management of carotid artery disease. J Vasc Surg. 2007 Aug;46(2):373–386. doi: 10.1016/j.jvs.2007.03.035
  • AbuRahma AF, Avgerinos ED, Chang RW, et al. The Society for Vascular Surgery implementation document for management of extracranial cerebrovascular disease. J Vasc Surg. 2022 Jan;75(1s):26s–98s. doi: 10.1016/j.jvs.2021.04.074
  • Sillesen H, Amarenco P, Hennerici MG, et al. Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) trial. Stroke. 2008 Dec;39(12):3297–3302. doi: 10.1161/STROKEAHA.108.516450
  • Amarenco P, Benavente O, Goldstein LB, et al. Results of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) trial by stroke subtypes. Stroke. 2009;40(4):1405–1409. doi: 10.1161/STROKEAHA.108.534107
  • High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549–559. doi: 10.1056/NEJMoa061894
  • Collins R, Armitage J, Parish S, et al. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004 Mar 6;363(9411):757–767.
  • Gitsels LA, Bakbergenuly I, Steel N, et al. Do statins reduce mortality in older people? Findings from a longitudinal study using primary care records. Fam Med Com Health. 2021 May;9(2):e000780. doi: 10.1136/fmch-2020-000780
  • Orkaby AR, Driver JA, Ho YL, et al. Association of statin use with all-cause and cardiovascular mortality in US veterans 75 years and older. JAMA. 2020 Jul 7;324(1):68–78. doi: 10.1001/jama.2020.7848
  • Foley TR, Singh GD, Kokkinidis DG, et al. High-intensity statin therapy is associated with improved survival in patients with peripheral artery disease. J Am Heart Assoc. 2017 Jul 15;6(7). doi: 10.1161/JAHA.117.005699
  • Bots SH, Onland-Moret NC, Jancev M, et al. Statins are associated with a large reduction in all-cause mortality in women from a cardiac outpatient population. Open Heart. 2022 Apr;9(1):e001900. doi: 10.1136/openhrt-2021-001900
  • Hackam DG. Optimal medical management of asymptomatic carotid stenosis. Stroke. 2021 Jun;52(6):2191–2198. doi: 10.1161/STROKEAHA.120.033994
  • O’Malley PG, Arnold MJ, Kelley C, et al. Management of dyslipidemia for cardiovascular disease risk reduction: synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline. Ann Intern Med. 2020 Nov 17;173(10):822–829. doi: 10.7326/M20-4648
  • Grundy SM, Stone NJ, Bailey AL, et al. 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. 2018 [2019 Jun 18];139(25):e1082–e1143.
  • Sudheer P, Vibha D, Misra S. Asymptomatic carotid stenosis: several guidelines with unclear answers. Ann Indian Acad Neurol. 2022;25(2):171–176. India. doi: 10.4103/aian.aian_566_21
  • Kim HW, Regenhardt RW, D’Amato SA, et al. Asymptomatic carotid artery stenosis: a summary of current state of evidence for revascularization and emerging high-risk features. J NeuroIntervent Surg. 2023;15(7):717–722. doi: 10.1136/jnis-2022-018732
  • Mach F, Baigent C, Catapano AL. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019 Nov;290:140–205. doi: 10.1016/j.atherosclerosis.2019.08.014
  • Brott TG, Halperin JL, Abbara S, et al. ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: a report of the American college of cardiology foundation/American heart association task force on practice guidelines, and the American stroke association, American association of neuroscience nurses, American association of neurological surgeons, American college of radiology, American society of neuroradiology, congress of neurological surgeons, society of atherosclerosis imaging and prevention, society for cardiovascular angiography and interventions, society of interventional radiology, society of neurointerventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. J Am Coll Cardiol. 2011 [2011 Feb 22];57(8):e16–94. doi: 10.1016/j.jacc.2010.11.006
  • food and drug administration(FDA). Statins cited 2023 May 6. Available from: https://www.fda.gov/drugs/information-drug-class/statins
  • Eckstein HH, Kühnl A, Berkefeld J, et al. Diagnosis, Treatment and Follow-up in Extracranial Carotid Stenosis. Dtsch Arztebl Int. 2020 Nov 20;117(47):801–807. doi: 10.3238/arztebl.2020.0801
  • Bonati LH, Kakkos S, Berkefeld J, et al. European stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis. Eur Stroke J. 2021;6(2):I–XLVII. doi: 10.1177/23969873211012121
  • Abbott AL, Paraskevas KI, Kakkos SK, et al. Systematic review of guidelines for the management of asymptomatic and symptomatic carotid stenosis. Stroke. 2015 Nov;46(11):3288–3301. doi: 10.1161/STROKEAHA.115.003390
  • Paraskevas KI, Mikhailidis DP, Antignani PL, et al. Comparison of recent practice guidelines for the management of patients with asymptomatic carotid stenosis. Angiology. 2022;73(10):903–910. doi: 10.1177/00033197221081914
  • Kleindorfer DO, Towfighi A, Chaturvedi S, et al. Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart association/American stroke association. Stroke. 2021;52(7):e364–e467. doi: 10.1161/STR.0000000000000375
  • Kashyap VS, So KL, Schneider PA, et al. One-year outcomes after transcarotid artery revascularization (TCAR) in the ROADSTER 2 trial. J Vasc Surg. 2022 Aug;76(2):466–473.e1. doi: 10.1016/j.jvs.2022.03.872
  • Heyer EJ, Mergeche JL, Bruce SS, et al. Statins reduce neurologic injury in asymptomatic carotid endarterectomy patients. Stroke. 2013 Apr;44(4):1150–1152. doi: 10.1161/STROKEAHA.111.000362
  • Texakalidis P, Giannopoulos S, Jonnalagadda AK, et al. Preoperative use of statins in carotid artery stenting: a systematic review and meta-analysis. J Endovasc Ther. 2018 Oct;25(5):624–631. doi: 10.1177/1526602818794030
  • Ballotta E, Toniato A, Farina F, et al. Effects of preoperative statin use on perioperative outcomes of carotid endarterectomy. Brain Behav. 2017 Jan;7(1):e00597. doi: 10.1002/brb3.597
  • Qiao L, Wang S, Jia Q, et al. Clinical efficacy and safety of statin treatment after carotid artery stenting. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3110–3115. doi: 10.1080/21691401.2019.1645149
  • Ironside N, Brenner D, Heyer E, et al. Systematic review and meta-analysis of perioperative and long-term outcomes in patients receiving statin therapy before carotid endarterectomy. Acta Neurochir (Wien). 2018;160(9):1761–1771. doi: 10.1007/s00701-018-3618-5
  • Cardounell SZ, Gonzalez L. Carotid artery Fibromuscular dysplasia. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.
  • Goodfriend SD, Tadi P, Koury R. Carotid artery dissection. Treasure Island, FL: StatPearls Publishing; 2023. https://www.ncbi.nlm.nih.gov/books/NBK430835/
  • Ma J, Khalidi N, Wierzbicki O, et al. Impact of diabetes, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use, and statin use on presentation and outcomes in patients with giant cell arteritis. Int J Of Rheum Dis. 2020 Aug;23(9):1233–1239. doi: 10.1111/1756-185X.13914
  • Ciofalo A, Gulotta G, Iannella G, et al. Giant cell arteritis (GCA): Pathogenesis, clinical aspects and treatment approaches. Curr Rheumatol Rev. 2019;15(4):259–268. doi: 10.2174/1573397115666190227194014
  • Mach F, Baigent C, Catapano AL, et al. ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European atherosclerosis Society (EAS). Eur Heart J. 2019;41(1):111–188. doi: 10.1093/eurheartj/ehz455
  • Navar AM, Peterson ED, Li S, et al. Prevalence and management of symptoms associated with statin therapy in community practice. Circulation. 2018;11(3):e004249. doi: 10.1161/CIRCOUTCOMES.117.004249
  • Rosenson RS, Baker SK, Jacobson TA, et al. An assessment by the statin muscle safety Task Force: 2014 update. J Clin Lipidol. 2014 May;8(3 Suppl):S58–71. doi: 10.1016/j.jacl.2014.03.004
  • Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy-European atherosclerosis Society Consensus Panel Statement on Assessment, aetiology and management. Eur Heart J. 2015 May 1;36(17):1012–1022. doi: 10.1093/eurheartj/ehv043
  • Wiklund O, Pirazzi C, Romeo S. Monitoring of lipids, enzymes, and creatine kinase in patients on lipid-lowering drug therapy. Curr Cardiol Rep. 2013 Sep;15(9):397. doi: 10.1007/s11886-013-0397-8
  • Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010 Feb 27;375(9716):735–742. doi: 10.1016/S0140-6736(09)61965-6
  • Egan A, Colman E. Weighing the benefits of high-dose simvastatin against the risk of myopathy. N Engl J Med. 2011 Jul 28;365(4):285–287. doi: 10.1056/NEJMp1106689
  • Sirtori CR, Mombelli G, Triolo M, et al. Clinical response to statins: mechanism(s) of variable activity and adverse effects. Ann Med. 2012 Aug;44(5):419–432. doi: 10.3109/07853890.2011.582135
  • Trompet S, Postmus I, Slagboom PE, et al. Non-response to (statin) therapy: the importance of distinguishing non-responders from non-adherers in pharmacogenetic studies. Eur J Clin Pharmacol. 2016 Apr;72(4):431–437. doi: 10.1007/s00228-015-1994-9
  • Brunham LR, Baker S, Mammen A, et al. Role of genetics in the prediction of statin-associated muscle symptoms and optimization of statin use and adherence. Cardiovasc Res. 2018 Jul 1;114(8):1073–1081. doi: 10.1093/cvr/cvy119
  • Kajinami K, Brousseau ME, Ordovas JM, et al. CYP3A4 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin in primary hypercholesterolemia. Am J Cardiol. 2004 Jan 1;93(1):104–107. doi: 10.1016/j.amjcard.2003.08.078
  • Bi Q, Zhou X, Lu Y, et al. Polymorphisms of the apolipoprotein E gene affect response to atorvastatin therapy in acute ischemic stroke [original research]. Front Cardiovasc Med. 2022 2022Nov 8;9. doi: 10.3389/fcvm.2022.1024014
  • Fiegenbaum M, da Silveira FR, Van der Sand CR, et al. The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. Clin Pharmacol Ther. 2005 Nov;78(5):551–558. doi: 10.1016/j.clpt.2005.08.003
  • Couvert P, Giral P, Dejager S, et al. Association between a frequent allele of the gene encoding OATP1B1 and enhanced LDL-lowering response to fluvastatin therapy. Pharmacogenomics. 2008 Sep;9(9):1217–1227. doi: 10.2217/14622416.9.9.1217
  • Igel M, Arnold KA, Niemi M, et al. Impact of the SLCO1B1 polymorphism on the pharmacokinetics and lipid-lowering efficacy of multiple-dose pravastatin. Clin Pharmacol Ther. 2006 May;79(5):419–426. doi: 10.1016/j.clpt.2006.01.010
  • Tompkins R, Schwartzbard A, Gianos E, et al. A current approach to statin intolerance. Clin Pharmacol Ther. 2014 Jul;96(1):74–80. doi: 10.1038/clpt.2014.84
  • Hua WJ, Hua WX, Fang HJ. The role of OATP1B1 and BCRP in pharmacokinetics and DDI of novel statins. Cardiovasc Ther. 2012 Oct;30(5):e234–41. doi: 10.1111/j.1755-5922.2011.00290.x
  • Rosenson RS, Miller K, Bayliss M, et al. The statin-associated muscle Symptom clinical index (SAMS-CI): revision for clinical use, content validation, and inter-rater reliability. Cardiovasc Drugs Ther. 2017 Apr;31(2):179–186. doi: 10.1007/s10557-017-6723-4
  • Link E, Parish S, Armitage J, et al. SLCO1B1 variants and statin-induced myopathy–a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789–799.
  • Brunham LR, Lansberg PJ, Zhang L, et al. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. Pharmacogenomics J. 2012 Jun;12(3):233–237. doi: 10.1038/tpj.2010.92
  • Frudakis TN, Thomas MJ, Ginjupalli SN, et al. CYP2D6*4 polymorphism is associated with statin-induced muscle effects. Pharmacogenet Genom. 2007 Sep;17(9):695–707. doi: 10.1097/FPC.0b013e328012d0a9
  • Wilke RA, Moore JH, Burmester JK. Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage. Pharmacogenet Genom. 2005 Jun;15(6):415–421. doi: 10.1097/01213011-200506000-00007
  • Keskitalo JE, Zolk O, Fromm MF, et al. ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther. 2009 Aug;86(2):197–203. doi: 10.1038/clpt.2009.79
  • Voora D, Shah SH, Spasojevic I, et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol. 2009 Oct 20;54(17):1609–1616. doi: 10.1016/j.jacc.2009.04.053
  • Carr DF, O’Meara H, Jorgensen AL, et al. SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink. Clin Pharmacol Ther. 2013 Dec;94(6):695–701. doi: 10.1038/clpt.2013.161
  • Roth EM, Davidson MH. PCSK9 inhibitors: mechanism of action, efficacy, and safety. Rev Cardiovasc Med. 2018;19(S1):S31–s46. doi: 10.3909/ricm19S1S0002
  • Liu A, Frostegård J. PCSK9 plays a novel immunological role in oxidized LDL-induced dendritic cell maturation and activation of T cells from human blood and atherosclerotic plaque. J Intern Med. 2018;284(2):193–210. doi: 10.1111/joim.12758
  • Marfella R, Prattichizzo F, Sardu C, et al. Evidence of an anti-inflammatory effect of PCSK9 inhibitors within the human atherosclerotic plaque. Atherosclerosis. 2023 Jun;29:117180.
  • Basiak M, Hachula M, Kosowski M, et al. The effect of PCSK9 inhibition on the stabilization of atherosclerotic plaque determined by biochemical and diagnostic imaging methods. Molecules. 2023;28(15):5928. doi: 10.3390/molecules28155928
  • Yang SH, Du Y, Li S, et al. Plasma PCSK9 level is unrelated to blood pressure and not associated independently with carotid intima-media thickness in hypertensives. Hypertens Res. 2016 Aug;39(8):598–605. doi: 10.1038/hr.2016.38
  • Chan DC, Pang J, McQuillan BM, et al. Plasma proprotein convertase subtilisin kexin type 9 as a predictor of carotid atherosclerosis in asymptomatic adults. Heart Lung Circ. 2016 May;25(5):520–525. doi: 10.1016/j.hlc.2015.10.017
  • Xie W, Liu J, Wang W, et al. Association between plasma PCSK9 levels and 10-year progression of carotid atherosclerosis beyond LDL-C: a cohort study. Int J Cardiol. 2016 Jul 15;215:293–298. doi: 10.1016/j.ijcard.2016.04.103
  • Posadas-Sánchez R, Vargas-Alarcón G, Pérez-Méndez Ó, et al. Increased carotid intima-media thickness in asymptomatic individuals is associated with the PCSK9 (rs2149041) gene polymorphism in the Mexican mestizo population: results of the GEA cohort. Life. 2022 Sep 30;12(10):1531. doi: 10.3390/life12101531
  • Liberale L, Carbone F, Bertolotto M, et al. Serum PCSK9 levels predict the occurrence of acute coronary syndromes in patients with severe carotid artery stenosis. Int J Cardiol. 2018 Jul 15;263:138–141. doi: 10.1016/j.ijcard.2018.03.081
  • Ogata A, Oho K, Matsumoto N, et al. Stabilization of vulnerable carotid plaques with proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab. Acta Neurochir (Wien). 2019 Mar;161(3):597–600. doi: 10.1007/s00701-019-03825-4
  • FDA. Cholesterol Medicines, [cited 2023 Aug 4]. Available from: https://www.fda.gov/media/161328/download?attachment
  • Aranzulla TC, Musumeci G. Morphological stabilization and regression of carotid plaque following therapy with evolocumab in a high-risk patient. Catheter Cardiovasc Interv. 2021 May 1;97(6):E835–e841. doi: 10.1002/ccd.29231
  • Lepor NE, Sun J, Canton G, et al. Regression in carotid plaque lipid content and neovasculature with PCSK9 inhibition: a time course study. Atherosclerosis. 2021 Jun;327:31–38.
  • Hoogeveen RM, Opstal TSJ, Kaiser Y, et al. PCSK9 antibody alirocumab attenuates arterial wall inflammation without changes in circulating inflammatory markers. JACC Cardiovasc Imaging. 2019 Dec;12(12):2571–2573. doi: 10.1016/j.jcmg.2019.06.022
  • Sun J, Lepor NE, Cantón G, et al. Serial magnetic resonance imaging detects a rapid reduction in plaque lipid content under PCSK9 inhibition with alirocumab. Int J Cardiovasc Imaging. 2021 Apr;37(4):1415–1422. doi: 10.1007/s10554-020-02115-w
  • Shingai Y, Kimura N, Doijiri R, et al. Effect of preoperative administration of proprotein convertase subtilisin/kexin type 9 inhibitor on carotid artery stenting. World Neurosurg. 2020 Mar;135:e36–e42.
  • Giugliano RP, Pedersen TR, Saver JL, et al. Stroke prevention with the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis. Stroke. 2020 May;51(5):1546–1554. doi: 10.1161/STROKEAHA.119.027759
  • Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017 May 4;376(18):1713–1722. doi: 10.1056/NEJMoa1615664
  • Huang YC, Chang CH, Tsai YH, et al. PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging. BMJ Open. 2022 Apr 29;12(4):e060068. doi: 10.1136/bmjopen-2021-060068
  • Kazi DS, Lu CY, Lin GA, et al. Nationwide coverage and cost-sharing for PCSK9 inhibitors among medicare part D plans. JAMA Cardiol. 2017;2(10):1164–1166. doi: 10.1001/jamacardio.2017.3051
  • Arrieta A, Page TF, Veledar E, et al. Economic evaluation of PCSK9 inhibitors in reducing cardiovascular risk from Health system and Private payer perspectives. PLoS One. 2017;12(1):e0169761. doi: 10.1371/journal.pone.0169761
  • Jukema JW, Zijlstra LE, Bhatt DL, et al. Effect of alirocumab on stroke in ODYSSEY OUTCOMES. Circulation. 2019 Dec 17;140(25):2054–2062. doi: 10.1161/CIRCULATIONAHA.119.043826
  • Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of Inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16):1507–1519. doi: 10.1056/NEJMoa1912387
  • Zhang Y, Chen H, Hong L, et al. Inclisiran: a new generation of lipid-lowering siRNA therapeutic. Front Pharmacol. 2023;14:1260921. doi: 10.3389/fphar.2023.1260921
  • Raschi E, Casula M, Cicero AFG, et al. Beyond statins: new pharmacological targets to decrease LDL-cholesterol and cardiovascular events. Pharmacol Ther. 2023 Oct;250:108507.
  • Rubino J, MacDougall DE, Sterling LR, et al. Lipid lowering with bempedoic acid added to a proprotein convertase subtilisin/kexin type 9 inhibitor therapy: a randomized, controlled trial. J Clin Lipidol. 2021 Jul;15(4):593–601. doi: 10.1016/j.jacl.2021.05.002
  • Stroes ESG, Bays HE, Banach M, et al. Bempedoic acid lowers high-sensitivity C-reactive protein and low-density lipoprotein cholesterol: analysis of pooled data from four phase 3 clinical trials. Atherosclerosis. 2023 May;373:1–9.
  • Chandramahanti S, Farzam K. Bempedoic acid. Treasure Island, FL: StatPearls Publishing; 2023. https://www.ncbi.nlm.nih.gov/books/NBK594232/
  • Dybiec J, Baran W, Dąbek B, et al. Advances in treatment of Dyslipidemia. Int J Mol Sci. 2023;24(17):13288. doi: 10.3390/ijms241713288
  • Migrino RQ, Bowers M, Harmann L, et al. Carotid plaque regression following 6-month statin therapy assessed by 3T cardiovascular magnetic resonance: comparison with ultrasound intima media thickness. J Cardiovasc Magn Reson. 2011;13(1). doi: 10.1186/1532-429X-13-37

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