[The association of lipid profile and bleeding in patients with minor stroke or transient ischemic attack on antiplatelet therapy: subgroup analysis of CHANCE]

Zhonghua Nei Ke Za Zhi. 2018 Oct 1;57(10):723-730. doi: 10.3760/cma.j.issn.0578-1426.2018.10.006.
[Article in Chinese]

Abstract

Objective: Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods: Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3 044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results: A total of 59 (1.9%) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95%CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04; 95%CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05; 95%CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions: Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.

目的: 探究轻型卒中或短暂性脑缺血发作(TIA)抗血小板治疗患者的血脂水平与出血之间的关系。 方法: 共纳入"氯吡格雷用于急性非致残性脑血管事件高危人群的疗效研究(CHANCE)"血样亚组3 044例急性轻型卒中或中高危TIA患者,检测总胆固醇、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯等血清指标。主要终点事件为90 d内的任意出血事件。次要终点事件为根据"全球应用链激酶和组织型纤溶酶原激活剂治疗闭塞冠状动脉研究(GUSTO)"定义的严重出血。采用多因素Cox比例风险模型分析血脂水平与任意出血/严重出血之间的关系。 结果: 90 d随访期内共发生了59例任意出血、30例严重出血事件。HDL-C、年龄与任意出血之间存在显著相关性:HDL-C每升高1 mmol/L,任意出血风险增加至2.16倍(HR=2.16,95%CI 1.17~4.00,P=0.014);年龄每增加1岁,任意出血风险增加至1.04倍(HR=1.04,95%CI 1.01~1.06,P=0.006)。另外,HDL-C与严重出血之间也具有显著相关性:HDL-C每升高1 mmol/L,严重出血风险增加至3.05倍(HR=3.05,95%CI 1.39~6.68,P=0.005)。总胆固醇、LDL-C和甘油三酯水平与任意出血/严重出血之间未见相关。抗血小板治疗分组与血脂不存在交互作用。 结论: 高HDL-C水平与急性轻型卒中/中高危TIA患者抗血小板治疗后的任意出血或严重出血独立相关。.

Keywords: Antiplatelet therapy; Hemorrhage; Ischemic attack, transient; Lipid; Stroke.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Clopidogrel
  • Drug Therapy, Combination
  • Hemorrhage / chemically induced*
  • Humans
  • Ischemic Attack, Transient / complications*
  • Ischemic Attack, Transient / drug therapy
  • Lipids / blood*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / complications*
  • Stroke / drug therapy
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Tissue Plasminogen Activator
  • Treatment Outcome

Substances

  • Lipids
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • PLAT protein, human
  • Tissue Plasminogen Activator
  • Ticlopidine
  • Aspirin