Antithrombotic therapy and bleeding risk in the era of aggressive lipid-lowering: current evidence, clinical implications, and future perspectives.

Abstract

ABSTRACT:

The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease (ASCVD) has been well established in recent large randomized outcome trials. Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive, current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol (LDL-C). Consequently, the emerging concept of "the lower the better" has become the paradigm of ASCVD prevention. However, there is evidence from observational studies of a U-shaped association between baseline LDL-C levels and all-cause mortality in population-based cohorts. Among East Asian populations, low LDL-C was associated with an increased risk for hemorrhagic stroke in patients not on antithrombotic therapy. Accumulating evidence showed that low LDL-C was associated with an enhanced bleeding risk in patients on dual antiplatelet therapy following percutaneous coronary intervention. Additionally, low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby, a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy. The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated. This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk, underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.

• Authors: Xin Zhou, Ziping Li, Hangkuan Liu, Yongle Li, Dong Zhao, Qing Yang
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 136 Issue 6 Pg. 645-652 (Mar 20 2023) ISSN: 2542-5641 [Electronic] China
• PMID: 36806078 (Publication Type: Review, Journal Article)
• Copyright: Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

Chemical References

• Cholesterol, LDL
• Fibrinolytic Agents
• Cholesterol
• Anticholesteremic Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors

Topics

• Humans
• Cholesterol, LDL
• Fibrinolytic Agents (adverse effects)
• Cholesterol
• Atherosclerosis (chemically induced)
• Treatment Outcome
• Anticholesteremic Agents (adverse effects)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)