J Stroke.  2024 May;26(2):231-241. 10.5853/jos.2024.00367.

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

• Xu Q
• Meng X
• Li H
• Xie X
• Jing J
• Lin J
• Jiang Y
• Wang Y
• Zhao X
• Li Z
• Liu L
• Wang A
• Wang Y

• KMID: 2556043
• DOI: http://doi.org/10.5853/jos.2024.00367

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.

Keyword

CHANCE-2; Stroke; Ticagrelor; Clopidogrel; Non?high-density lipoprotein cholesterol

Figure

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  Figure 1. Flowchart of the study design. HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol.

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  Figure 2. Cumulative probability of stroke recurrence in patients at 3-month follow-up according to non-HDL-C levels and dual antiplatelet therapy. (A) Non-HDL-C and stroke. (B) Low non-HDL-C. (C) High non-HDL-C. Low non-HDL-C represents non-HDL-C <3.5 mmol/L; High non-HDL-C represents non-HDL-C ≥3.5 mmol/L. HDL-C, high-density lipoprotein cholesterol; CI, confidence interval.

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  Figure 3. Effects of non-HDL-C as a continuous variable on the efficacy of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence within 90 days. The shaded areas represent the 95% confidence intervals. non-HDL-C, non-high-density lipoprotein cholesterol; CI, confidence interval; HR, hazard ratio.

Reference

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