Vol. 2 No. 1 (2025)

Research Articles

Causal Relationship between PCSK9 Inhibitor and Atrial Fibrillation/ A Drug Target Mendelian Randomization Study

Published 2025-05-31

  • Xinlong Zhang
    • ,
  • Zihong Yang
    • ,
  • Rongjie Huang

Xinlong Zhang
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanling, China

Zihong Yang
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanling, China；People's Hospital of Bobai County, Yulin, China

Rongjie Huang
Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanling, China；Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention, Nanling, China; Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanling, China

Abstract

In addition to reducing cholesterol levels, proprotein convertase subtilis kexin 9 (PCSK9) inhibitors exhibit pleiotropic effects, including potential prevention of atrial fibrillation; however, their impact on this cardiac arrhythmia remains controversial. To investigate this relationship, we employed drug-target Mendelian randomization (MR) analysis, collecting single-nucleotide polymorphisms (SNPs) of PCSK9 from published genome-wide association study statistics. Our findings demonstrated that PCSK9 inhibitors significantly reduced the risk of atrial fibrillation (OR [95%CI] = 0.59 [0.45 to 0.78], p=1.38×10-4). For comparison, we also evaluated the effects of 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors (targeting statins), using coronary heart disease risk as a positive control, and observed that HMGCR inhibitors may conversely increase the risk of atrial fibrillation. These results suggest that PCSK9 inhibitors confer a protective effect against atrial fibrillation, while HMGCR inhibitors could pose a potential risk for this condition.

Keywords

Drug-target Mendelian , randomization, PCSK9, HMGCR, Atrial Fibrillation

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