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Research Paper|Volume 14, Issue 17|pp 6975—6992

Use of nicorandil is associated with increased risk of incident atrial fibrillation

Chien-Chang Lee1,2, Sheng-Nan Chang3, Babak Tehrani4, Sot Shih-Hung Liu1, Chia-Ying Chan5, Wan-Ting Hsu6, Tzu-Yun Huang5, Pang-Shuo Huang3, Juey-Jen Hwang7, Jien-Jiun Chen3, Chia-Ti Tsai7
  • 1Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • 2Center of Intelligent Healthcare, National Taiwan University Hospital, Taipei, Taiwan
  • 3Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
  • 4Department of Medicine, Brown University/Rhode Island Hospital, Providence, RI 02912, USA
  • 5Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • 6Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
  • 7Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Received: March 22, 2022Accepted: August 17, 2022Published: September 9, 2022
https://doi.org/10.18632/aging.204259

Copyright: © 2022 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Nicorandil will activate ATP-sensitive potassium channel (KATP). However, activation of potassium channels plays an important role in the mechanism of atrial fibrillation (AF) or atrial flutter (AFL). Whether use of nicorandil might contribute to initiation and/or perpetuation of AF/AFL remained unknown. We determined the relationship between use of nicorandil and risk of atrial fibrillation and determined its molecular mechanism.

Methods: We performed a nested case-control study using a cohort from the National Health Insurance Research Database (NHIRD) of Taiwan. The association between nicorandil use and risk of atrial fibrillation/flutter was estimated by logistic regression model. We also performed molecular, cellular and animal studies to explain the association.

Results: A total of 715 individuals who experienced AF/atrial flutter were matched to 72,215 controls. New use of nicorandil was found to be associated with increased risk for AF/AFL (odds ratio [OR], 2.34; 95% CI 1.07–5.13) compared to nitrate use. We found the expression of KATP subunits Kir6.2 and SUR2A in human and rat left atrial tissues. Furthermore, nicorandil directly shortened action potential duration (APD) in rat left atrium and shortened the QT interval of cultured human induced pluripotent stem cell (iPSC) derived cardiomyocytes (iPSC-CMs).

Conclusions: Use of nicorandil was found to be associated with increased risk of AF/AFL. We also showed the expression of KATP subunits in human atria, and a possible mechanism that use of nicorandil increases the risk of AF through activation of KATP and shortening of atrial APD.