The Influence of Non-High-Density Lipoprotein Cholesterol on the Efficacy of Genotype-Guided Dual Antiplatelet Therapy in Preventing Stroke Recurrence

Overview

Journal J Stroke

Date 2024 Jun 5

PMID 38836270

Authors

Qin Xu

Xia Meng

Hao Li

Xuewei Xie

Jing Jing

Jinxi Lin

Yong Jiang

Yilong Wang

Xingquan Zhao

Zixiao Li

Liping Liu

Anxin Wang

Yongjun Wang

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence.

Methods: This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days.

Results: Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40-0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67-1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425).

Conclusion: CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Citing Articles

Non-high-density Lipoprotein Cholesterol for Secondary Prevention after Minor Stroke.

Wang Y, Jiang Z, Wu S J Atheroscler Thromb. 2024; 32(2):122-124.

PMID: 39551491 PMC: 11802247. DOI: 10.5551/jat.ED272.

References

Jager B, Piackova E, Haller P, Andric T, Kahl B, Christ G . Increased platelet reactivity in dyslipidemic patients with coronary artery disease on dual anti-platelet therapy. Arch Med Sci. 2019; 15(1):65-71. PMC: 6348363. DOI: 10.5114/aoms.2018.81035. View

Bornstein N, Karepov V, Aronovich B, Gorbulev A, Treves T, Korczyn A . Failure of aspirin treatment after stroke. Stroke. 1994; 25(2):275-7. DOI: 10.1161/01.str.25.2.275. View

Carvalho A, Colman R, Lees R . Platelet function in hyperlipoproteinemia. N Engl J Med. 1974; 290(8):434-8. DOI: 10.1056/NEJM197402212900805. View

Helgadottir A, Thorleifsson G, Snaebjarnarson A, Stefansdottir L, Sveinbjornsson G, Tragante V . Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles: a Mendelian randomization analysis. Eur J Prev Cardiol. 2022; 29(18):2374-2385. DOI: 10.1093/eurjpc/zwac219. View

Kleindorfer D, Towfighi A, Chaturvedi S, Cockroft K, Gutierrez J, Lombardi-Hill D . 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. 2021; 52(7):e364-e467. DOI: 10.1161/STR.0000000000000375. View

Kameda S, Sakata T, Kokubo Y, Mitsuguro M, Okamoto A, Sano M . Association of platelet aggregation with lipid levels in the Japanese population: the Suita study. J Atheroscler Thromb. 2011; 18(7):560-7. DOI: 10.5551/jat.6288. View

Kim J, Park C, Ahn K, Cho J, Choi K, Kang J . Non-HDL cholesterol is an independent risk factor for aspirin resistance in obese patients with type 2 diabetes. Atherosclerosis. 2014; 234(1):146-51. DOI: 10.1016/j.atherosclerosis.2014.01.015. View

Elshazly M, Martin S, Blaha M, Joshi P, Toth P, McEvoy J . Non-high-density lipoprotein cholesterol, guideline targets, and population percentiles for secondary prevention in 1.3 million adults: the VLDL-2 study (very large database of lipids). J Am Coll Cardiol. 2013; 62(21):1960-1965. DOI: 10.1016/j.jacc.2013.07.045. View

Wang G, Jing J, Wang A, Zhang X, Zhao X, Li Z . Non-High-Density Lipoprotein Cholesterol Predicts Adverse Outcomes in Acute Ischemic Stroke. Stroke. 2021; 52(6):2035-2042. DOI: 10.1161/STROKEAHA.120.030783. View

10.

Wang N, Tall A . Cholesterol in platelet biogenesis and activation. Blood. 2016; 127(16):1949-53. PMC: 4841038. DOI: 10.1182/blood-2016-01-631259. View

11.

Li J, Wang Y, Wang D, Lin J, Wang A, Zhao X . Glycated albumin predicts the effect of dual and single antiplatelet therapy on recurrent stroke. Neurology. 2015; 84(13):1330-6. DOI: 10.1212/WNL.0000000000001421. View

12.

Grundy S, Stone N, Bailey A, Beam C, Birtcher K, Blumenthal R . 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. 2018; 139(25):e1082-e1143. PMC: 7403606. DOI: 10.1161/CIR.0000000000000625. View

13.

Bobescu E, Covaciu A, Rus H, Rogozea L, Badea M, Marceanu L . Low Response to Clopidogrel in Coronary Artery Disease. Am J Ther. 2019; 27(2):e133-e141. DOI: 10.1097/MJT.0000000000001099. View

14.

Marnane M, Prendeville S, McDonnell C, Noone I, Barry M, Crowe M . Plaque inflammation and unstable morphology are associated with early stroke recurrence in symptomatic carotid stenosis. Stroke. 2014; 45(3):801-6. DOI: 10.1161/STROKEAHA.113.003657. View

15.

Scioli M, Storti G, DAmico F, Rodriguez Guzman R, Centofanti F, Doldo E . Oxidative Stress and New Pathogenetic Mechanisms in Endothelial Dysfunction: Potential Diagnostic Biomarkers and Therapeutic Targets. J Clin Med. 2020; 9(6). PMC: 7355625. DOI: 10.3390/jcm9061995. View

16.

Wang Y, Johnston C, Bath P, Meng X, Jing J, Xie X . Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial. Stroke Vasc Neurol. 2021; 6(2):280-285. PMC: 8258075. DOI: 10.1136/svn-2020-000791. View

17.

Kamtchum-Tatuene J, Noubiap J, Wilman A, Saqqur M, Shuaib A, Jickling G . Prevalence of High-risk Plaques and Risk of Stroke in Patients With Asymptomatic Carotid Stenosis: A Meta-analysis. JAMA Neurol. 2020; 77(12):1524-1535. PMC: 7400201. DOI: 10.1001/jamaneurol.2020.2658. View

18.

Shen H, Herzog W, Drolet M, Pakyz R, Newcomer S, Sack P . Aspirin Resistance in healthy drug-naive men versus women (from the Heredity and Phenotype Intervention Heart Study). Am J Cardiol. 2009; 104(4):606-12. PMC: 3674572. DOI: 10.1016/j.amjcard.2009.04.027. View

19.

Xu J, Tao Y, Li H, Gu H, Xie X, Meng X . Different levels of blood pressure, different benefit from dual antiplatelet therapy in minor stroke or TIA patients. Sci Rep. 2017; 7(1):3884. PMC: 5478626. DOI: 10.1038/s41598-017-04169-8. View

20.

. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993; 329(10):673-82. DOI: 10.1056/NEJM199309023291001. View