The Role of Lipid-Lowering Therapy in Post-Stroke Patients: Update and Recommendations

GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):439–58.

GBD 2016 Lifetime Risk of Stroke Collaborators, Feigin VL, Nguyen G, Cercy K, Johnson CO, Alam T, et al. Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016. N Engl J Med. 2018;379(25):2429–37.

Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139-596.

Article  PubMed  Google Scholar 

• Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, et al. 2021 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. Lippincott Williams and Wilkins; 2021. p. E364–467. Updated US guidelines on secondary prevention of stroke.

Hackam DG, Spence JD. Combining multiple approaches for the secondary prevention of vascular events after stroke: a quantitative modeling study. Stroke. 2007;38(6):1881–5.

Article  PubMed  Google Scholar 

•• Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Béjot Y, et al. A comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020;382(1):9–19. Recent RCT demonstrating the added benefit of a strategy that targets lower LDL levels in patients with prior cerebrovascular events.

Article  CAS  PubMed  Google Scholar 

Zhang Y, Tuomilehto J, Jousilahti P, Wang Y, Antikainen R, Hu G. Total and high-density lipoprotein cholesterol and stroke risk. Stroke. 2012;43(7):1768–74.

Article  PubMed  Google Scholar 

Toth PP, Granowitz C, Hull M, Liassou D, Anderson A, Philip S. High triglycerides are associated with increased cardiovascular events, medical costs, and resource use: a real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk. J Am Heart Assoc. 2018;7(15):e008740.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Vol. 139, Circulation.Lippincott Williams and Wilkins; 2019. p. E1046–81.

Bhatt DL, Eagle KA, Ohman EM, Hirsch AT, Goto S, Mahoney EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010;304(12):1350–7.

Article  CAS  PubMed  Google Scholar 

Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22.

Article  CAS  PubMed  Google Scholar 

Amarenco P, Bogousslavsky J, Callahan A, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549–59.

Article  CAS  PubMed  Google Scholar 

Wang X, Dong Y, Qi X, Huang C, Hou L. Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke. 2013;44(7):1833–9.

Article  CAS  PubMed  Google Scholar 

Amarenco P, Goldstein LB, Szarek M, Sillesen H, Rudolph AE, Callahan A, et al. Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke. 2007;38(12):3198–204.

Article  CAS  PubMed  Google Scholar 

Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.

Article  Google Scholar 

Tramacere I, Boncoraglio GB, Banzi R, del Giovane C, Kwag KH, Squizzato A, et al. Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis. BMC Med. 2019;17(1):67.

Article  PubMed  PubMed Central  Google Scholar 

Gladstone DJ, Patrice Lindsay M, Douketis J, Smith EE, Dowlatshahi D, Wein T, et al. Canadian Stroke Best Practice recommendations: secondary prevention of stroke update 2020 – ADDENDUM. Canadian J Neurol Sci/J Canadien des Sciences Neurologiques. 2022;3:1–1.

Google Scholar 

Dawson J, Béjot Y, Christensen LM, de Marchis GM, Dichgans M, Hagberg G, et al. European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack. Eur Stroke J. 2022;7(3):I–II.

Article  PubMed  PubMed Central  Google Scholar 

Nanna MG, Navar AM, Zakroysky P, Xiang Q, Goldberg AC, Robinson J, et al. Association of patient perceptions of cardiovascular risk and beliefs on statin drugs with racial differences in statin use: insights from the patient and provider assessment of lipid management registry. JAMA Cardiol. 2018;3(8):739–48.

Article  PubMed  PubMed Central  Google Scholar 

Dearborn-Tomazos JL, Hu X, Bravata DM, Phadke MA, Baye FM, Myers LJ, et al. Deintensification or no statin treatment is associated with higher mortality in patients with ischemic stroke or transient ischemic attack. Stroke. 2021;52(8):2521–9. https://doi.org/10.1161/STROKEAHA.120.030089.

Oyama K, Giugliano RP, Blazing MA, Park JG, Tershakovec AM, Sabatine MS, et al. Baseline low-density lipoprotein cholesterol and clinical outcomes of combining ezetimibe with statin therapy in IMPROVE-IT. J Am Coll Cardiol. 2021;78(15):1499–507.

Article  CAS  PubMed  Google Scholar 

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97.

Article  CAS  PubMed  Google Scholar 

Bohula EA, Wiviott SD, Giugliano RP, Blazing MA, Park JG, Murphy SA, et al. Prevention of stroke with the addition of ezetimibe to statin therapy in patients with acute coronary syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation. 2017;136(25):2440–50.

Article  CAS  PubMed  Google Scholar 

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22.

Article  CAS  PubMed  Google Scholar 

Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097–107.

Article  CAS  PubMed  Google Scholar 

Jukema JW, Zijlstra LE, Bhatt DL, Bittner VA, Diaz R, Drexel H, et al. Effect of alirocumab on stroke in ODYSSEY OUTCOMES. Circulation. 2019;140(25):2054–62.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ray KK, Bays HE, Catapano AL, Lalwani ND, Bloedon LT, Sterling LR, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med. 2019;380(11):1022–32.

Article  CAS  PubMed  Google Scholar 

Goldberg AC, Leiter LA, Stroes ESG, Baum SJ, Hanselman JC, Bloedon LT, et al. Effect of bempedoic acid vs placebo added to maximally tolerated statins on low-density lipoprotein cholesterol in patients at high risk for cardiovascular disease: the CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019;322(18):1780–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nissen SE, Menon V, Nicholls SJ, Brennan D, Laffin L, Ridker P, et al. Bempedoic acid for primary prevention of cardiovascular events in statin-intolerant patients. JAMA. 2023

Klempfner R, Erez A, Sagit BZ, Goldenberg I, Fisman E, Kopel E, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the bezafibrate infarction prevention study and registry. Circ Cardiovasc Qual Outcomes. 2016;9(2):100–8.

Article  PubMed  Google Scholar 

Nichols GA, Philip S, Reynolds K, Granowitz CB, Fazio S. Increased cardiovascular risk in hypertriglyceridemic patients with statin-controlled LDL cholesterol. J Clin Endocrinol Metab. 2018;103(8):3019–27.

Article  PubMed  Google Scholar 

Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090–8.

Article  CAS  PubMed  Google Scholar 

Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals. JAMA Cardiol. 2018;3(3):225–34.

Article  PubMed  Google Scholar 

Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH Randomized Clinical Trial. JAMA. 2020;324(22):2268–80.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kalstad AA, Myhre PL, Laake K, Tveit SH, Schmidt EB, Smith P, et al. Effects of n-3 fatty acid supplements in elderly patients after myocardial infarction: a randomized, controlled trial. Circulation. 2021;143(6):528–39.

Article  CAS  PubMed  Google Scholar 

Kastelein JJP, Stroes ESG. FISHing for the miracle of eicosapentaenoic acid. N Engl J Med. 2019;380(1):89–90.

Article  PubMed  Google Scholar 

Nissen SE. When Is a Placebo Not a Placebo. JAMA Cardiol. 2022;7(12):1183–4. https://doi.org/10.1001/jamacardio.2022.3698.

Article  PubMed  Google Scholar 

Rudolph DA, Hald SM, García Rodríguez LA, Möller S, Hallas J, Goldstein LB, Gaist D. Association of long-term statin use with the risk of intracerebral hemorrhage: A Danish nationwide case-control study. Neurology. 2022:10.1212/WNL.0000000000200713. https://doi.org/10.1212/WNL.0000000000200713.

Saito I, Yamagishi K, Kokubo Y, Yatsuya H, Iso H, Sawada N, et al. Non-high-density lipoprotein cholesterol and risk of stroke subtypes and coronary heart disease: The Japan Public Health Center-Based Prospective (JPHC) Study. J Atheroscler Thromb. 2020;27(4):363–74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pezzini A, Grassi M, Iacoviello L, Zedde M, Marcheselli S, Silvestrelli G, et al. Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy). J Neurol Neurosurg Psychiatry. 2016;87(9):924–9.

Article  PubMed 

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