Ticagrelor is currently considered a first-line choice in dual antiplatelet therapy (DAPT) following revascularization of acute coronary syndrome (ACS). However, its use is correlated with an increased incidence of two side effects, dyspnea and bradyarrhythmias, whose molecular mechanisms have not yet been defined with certainty and, consequently, neither of the therapeutic decisions they imply. We report the case of a patient with acute myocardial infarction treated with ticagrelor and aspirin as oral antithrombotic therapy after primary percutaneous coronary intervention (PCI), manifesting in a significant bradyarrhythmic episode that required a switch of antiplatelet therapy. Starting from this case report, this article aims to gather the currently available evidence regarding the molecular mechanisms underlying these side effects and propose possible decision-making algorithms regarding their management in clinical practice.

A 47-year-old female presented to emergency clinic due to non-ST-elevation myocardial infarction (NSTEMI). After receiving acetylsalicylic acid, a loading dose of ticagrelor 180 mg and intravenous unfractionated heparin, she underwent successful placement of drug eluting stent on the distal part of non-dominant left circumflex artery. The patient had no pre-existing atrioventricular (AV) block and did not use AV blocking agent. Approximately 10 h after taking a loading dose of ticagrelor, baseline normal rhythm degenerated to the first and then complete AV block, with mild dizziness. Following cessation of ticagrelor, cardiac rhythm returned to normal level within 2 days. The close monitoring of patients after starting ticagrelor is imperative, so ticagrelor may result in advanced conduction disorders. Here, we report a patient who developed various types of AV block associated with the ticagrelor taken during successful percutaneous coronary intervention for NSTEMI. We also reviewed the literature on the association between ticagrelor use and conduction abnormalities.

Ticagrelor is a potent, direct P2Y12 antagonist with rapid onset of action and intense platelet inhibition, indicated in patients with acute coronary syndromes (ACS). This drug is usually well tolerated, but some patients experience serious adverse effects: Major bleeding; gastrointestinal disturbances; dyspnoea; ventricular pauses > 3 s. Given the unexpected high incidence of bradyarrhythmias, a PLATO substudy monitored this side effect, showing that ticagrelor was associated with an increase in the rate of sinus bradycardia and sinus arrest compared to clopidogrel. This side effect was usually transient, asymptomatic and not associated with higher incidence of severe atrioventricular (AV) block or pacemaker needs. A panel of experts from Food and Drug Administration did not consider bradyarrhythmias a serious problem in clinical practice and, accordingly, current labeling of the drug does not give any precaution or contraindication regarding this issue. However, recently some articles have described ACS patients with high-degree, life-threatening, AV block requiring drug discontinuation and, in some cases, pacemaker implantation. In this paper, we describe and discuss five published case reports of severe AV block following ticagrelor therapy and two other cases managed in our Hospital. The analysis of literature suggests that, although rarely, ticagrelor can be associated with life-threatening AV block. Caution and careful monitoring are required especially in patients with already compromised conduction system and/or treated with AV blocking agents. Future studies, with long-term rhythm monitoring, would help to define the outcome of patients at higher risk of developing this complication.

Ticagrelor is an antiplatelet agent prescribed to prevent the development of adverse cardiac events after acute coronary syndrome (ACS). According to the PLATO trial, ticagrelor is associated with ventricular pauses in the first week of treatment; however, these episodes were felt to be asymptomatic and nonfatal to the patient. We present a case of ticagrelor related second-degree type II heart block causing severe dizziness and diaphoresis that resolved after discontinuation of the medication.