The Effect of Platelet Activity, ABCB1 Genetic Polymorphism, and Renal Function on the Development of Ticagrelor-Related Dyspnea in Patients with Acute Coronary Syndrome

Abstract

Purpose

The aim of this study was to determine the effect of ABCB1 genetic polymorphism and renal function on the occurrence of ticagrelor-related dyspnea.

Patients and Methods

A total of 299 patients with acute with type 1, 2, or 3 myocardial infarction (with and without ST-segment elevation), who underwent coronary angiography and PTCA with stent implantation and were treated with antiplatelet drugs (ticagrelor and aspirin), were enrolled in this prospective study. For all enrolled patient’s platelet aggregation (induction with high-sensitivity adenosine diphosphate, ADP HS) testing was performed using a MULTIPLATE^® analyzer. Venous blood was also collected for genotyping.

Results

Patients experiencing ticagrelor-related dyspnea had lower ADP HS value (ADP HS ≤ 19.5 U; OR = 2.254; P = 0.009), higher creatinine concentration (>90 µmol/l; OR = 3.414; P = 0.019), and lower GFR value (<60 mL/min/1.73 m²; OR = 2.211; P = 0.035). ABCB1 T allele was associated with ticagrelor-related dyspnea (OR = 2.550; P = 0.04).

Conclusion

Ticagrelor-related dyspnea was found to be related to low platelet aggregation, increased plasma creatinine concentration, decreased GFR, and ABCB1 T allele. Carriers of the ABCB1 T allele had a higher plasma creatinine concentration that could be associated with an inhibitory effect of ticagrelor on P-glycoprotein function.

Keywords:

• ticagrelor
• ticagrelor pharmacogenomics
• ticagrelor related dyspnea
• ABCB1 gene polymorphisms
• platelet aggregation

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by Kaunas Regional Biomedical Research Ethics Committee (permission No. P1-BE-2-19/2019, dated 10 June 2019).

Data Sharing Statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical restrictions and data protection policies.

Informed Consent Statement

Informed consent was obtained from all subjects involved in this study.

Disclosure

The author reports no conflicts of interest in this work.

Additional information

Funding

This research received no external funding.