Abstract
BACKGROUND: Ticagrelor is a reversible, direct inhibitor of the platelet adenosine diphosphate (P2Y12) receptor, widely used in combination with acetylsalicylic acid (ASA) as dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) to prevent cardiovascular events. Despite its well-established efficacy, ticagrelor may cause adverse effects ranging from common ones (e.g., bleeding, dyspnea) to rare but potentially serious reactions such as bradyarrhythmias. These rare events are likely related to elevated adenosine levels secondary to inhibition of the human equilibrative nucleoside transporter 1 (hENT1). METHODS: We describe two clinical cases of ticagrelor-associated bradyarrhythmia observed in patients following ACS. Both cases were analyzed in terms of clinical presentation, ECG findings, management strategy, and outcomes after discontinuation of the drug. RESULTS: The first case concerns a 67-year-old woman with non-ST-segment elevation myocardial infarction (NSTEMI) who developed complete atrioventricular block (third degree) with a 45 s asystolic pause and syncope. The second case involves a 67-year-old man with anterior ST-segment elevation myocardial infarction (STEMI) who experienced recurrent sinus pauses lasting up to 5 s. In both cases, symptoms resolved following ticagrelor discontinuation and theophylline administration. No recurrence of arrhythmia was observed after switching to prasugrel. CONCLUSIONS: Ticagrelor-induced bradyarrhythmias, although rare, represent an important and reversible adverse effect that clinicians should be aware of, particularly during the early post-ACS phase. Prompt recognition and drug withdrawal may prevent severe outcomes and avoid unnecessary interventions such as pacemaker implantation. Further studies are warranted to identify patient-specific risk factors predisposing to ticagrelor-related conduction disturbances.