Genetic influence on bleeding and over-anticoagulation risk in patients undergoing warfarin treatment after heart valve replacements

ABSTRACT

Background: Warfarin acts in heart valve replacement patients to minimize thromboembolic complications. We investigated whether patients can be distinguished based on their genotypes to efficiently and safely administer warfarin therapy after heart valve replacements.

Research design and methods: A retrospective analysis was conducted in patients with warfarin therapy who underwent elective heart valve replacements between January 2013 and September 2018. The patients were divided into normal, sensitive, and highly sensitive bins based on their CYP2C9 and VKORC1 genotypes. The primary endpoints were over-anticoagulation and overt bleeding.

Results: 375 patients were enrolled, with 65 classified as normal, 281 as sensitive, and 29 as highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders spent more time on over-anticoagulation in the first 28 (P < 0.001) and 90 (P = 0.001) days; experienced more frequent bleeding events in the first 28 days (P = 0.029; OR, 2.18; 95% CI, 1.15–4.13); required lower warfarin doses to obtain stable INR (P < 0.001); had higher warfarin sensitivity indices (P < 0.001).

Conclusion: Predicting evidence have been obtained with CYP2C9 and VKORC1 genotypes in identifying heart valve replacement patients with higher efficient sensitivity and with a higher risk of bleeding and over-anticoagulation.

KEYWORDS:

• Bleeding
• CYP2C9
• Heart valve replacement
• Over-anticoagulation
• VKORC1
• Warfarin

Author contributions

L. Zhou, Y.L. Ding, Y. Gao, B.W. Yang, J.A. Bao and J.J. Ma participated in the design of the trial and study methodology. L. Zhou followed up with patients and collected data. Y.L. Ding and B.W. Yang reviewed the complications. J.J. Ma and Y. Gao performed data analysis. J.A. Bao and J.J. Ma wrote the first draft of the manuscript and made critical revisions. All authors reviewed the manuscript and approved the final version of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.