Ticagrelor therapy and atrioventricular block: Do we need to worry?

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 lifethreatening 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.