Heart Block Caused by Ticagrelor Use in a Patient Who Underwent Adenosine Diastolic Fractional Reserve Assessment: A Case Report

Abstract

Ticagrelor is a direct and rapid-acting antagonist of the P2Y12-adenosine diphosphate receptor found on platelets. The drug is recommended as a first-line antiplatelet agent in patients with acute coronary syndromes, as evidenced in its superiority compared to clopidogrel according to the Platelet Inhibition and Patient Outcomes study. Specifically, the mechanism of action has been proven to show higher inhibition and less variability in its action on P2Y12 receptors compared to clopidogrel. Additionally, ticagrelor inhibits the equilibrative nucleoside transporter 1 adenosine transporter protein leading to an increased concentration of adenosine in the blood, particularly at sites of ischemia. This effect increases the biological efficacy of ticagrelor in terms of cardioprotection, anticoagulation effects, and anti-inflammatory effects. However, the effects are also thought to be responsible for some of the adverse pharmacological effects reported with ticagrelor, such as bradycardia and ventricular pauses > 3 seconds. Herein, we report a case of recurrent sinus arrest and ventricular asystole in a patient pre-treated with ticagrelor and subsequent physiological assessment of a coronary lesion with fractional flow reserve using intravenous adenosine infusion.

A disproportionality analysis of FDA adverse event reporting system (FAERS) events for ticagrelor

“…Among them, bradycardia is mentioned in the drug labels/datasheets. There are multiple case reports about bradycardia-related ADEs caused by ticagrelor and serious bradyarrhythmia, both as early effects or in a delayed fashion ( Al-Bayati et al, 2021 ; Aranganathan et al, 2021 ; Kotaru and Kalavakunta, 2021 ). The EMA identified ticagrelor-related bradyarrhythmia as a potential safety issue and included it in the European Risk Management Plan in 2011 ( Pujade et al, 2020 ).…”

“…Furthermore, new safety information about central sleep apnea (CSA) and Cheyne-Stokes respiration was added in September 2020, and a new section about CSA and Cheyne-Stokes respiration was added to the “WARNINGS AND PRECAUTIONS” section in August 2021 ( FDA, 2020 ; FDA, 2021 ). Over the past years, several case reports have emerged showing the possibility of serious ticagrelor-induced bradyarrhythmia ( Al-Bayati et al, 2021 ; Aranganathan et al, 2021 ; Kotaru and Kalavakunta, 2021 ). A sub-study of the PLATO trial showed that more patients treated with ticagrelor had ventricular pauses compared to clopidogrel-treated patients, but there were no apparent clinical consequences related to the increase in ventricular pauses in patients receiving ticagrelor ( Scirica et al, 2011 ).…”