LDL cholesterol levels and in-hospital bleeding in patients on high-intensity antithrombotic therapy: findings from the CCC-ACS project.

Abstract

AIMS:

Emerging evidence has linked cholesterol metabolism with platelet responsiveness. We sought to examine the dose-response relationship between low-density lipoprotein cholesterol (LDL-C) and major in-hospital bleeds in acute coronary syndrome (ACS) patients.

METHODS AND RESULTS:

Among 42 378 ACS patients treated with percutaneous coronary intervention (PCI) enrolled in 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with the higher risk at lower LDL-C levels. No dose-response relationship was identified for ischaemic events and mortality. A threshold value of LDL-C <70 mg/dL was associated with an increased risk for major bleeds (adjusted odds ratio: 1.49; 95% confidence interval: 1.21-1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at <88 mg/dL, whereas for clopidogrel-treated patients, the threshold was <54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, but no difference at higher LDL-C levels.

CONCLUSIONS:

In a nationwide ACS registry, a non-linear association was identified between LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. As the potential for confounding may exist, further studies are warranted.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT02306616.

• Authors: Qing Yang, Dongdong Sun, Chongzhe Pei, Yuhong Zeng, Zhuoqun Wang, Ziping Li, Yongchen Hao, Xiwen Song, Yongle Li, Gang Liu, Yida Tang, Sidney C Smith, Yaling Han, Yong Huo, Junbo Ge, Changsheng Ma, Gregg C Fonarow, Louise Morgan, Jing Liu, Jun Liu, Mengge Zhou, Dong Zhao, Yujie Zhou, Xin Zhou, CCC-ACS Investigators
• Journal: European heart journal (Eur Heart J) Vol. 42 Issue 33 Pg. 3175-3186 (08 31 2021) ISSN: 1522-9645 [Electronic] England
• PMID: 34347859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected].

Chemical References

• Cholesterol, LDL
• Fibrinolytic Agents
• Platelet Aggregation Inhibitors

Topics

• Acute Coronary Syndrome (drug therapy)
• Cholesterol, LDL
• Fibrinolytic Agents (adverse effects)
• Hospitals
• Humans
• Percutaneous Coronary Intervention
• Platelet Aggregation Inhibitors (adverse effects)
• Treatment Outcome