The Incidence of Bradyarrhythmias and Clinical Bradyarrhythmic Events in Patients With Acute Coronary Syndromes Treated With Ticagrelor or Clopidogrel in the PLATO (Platelet Inhibition and Patient Outcomes) Trial: Results of the Continuous Electrocardiographic Assessment Substudy

Study Questions:

Does ticagrelor cause bradyarrhythmias?


This was a substudy of the PLATO trial, in which 2,908 patients (mean age 63) with acute coronary syndrome (ACS) were randomly assigned to 1 year of therapy with ticagrelor (n = 1,472) or clopidogrel (n = 1,436), and underwent 7-day Holter monitoring at randomization and at 1-4 weeks of follow-up. The primary endpoint was the incidence of ventricular pauses ≥3 seconds.


A ventricular pause ≥3 seconds in duration occurred significantly more often during the first week of therapy with ticagrelor (5.8%) than with clopidogrel (3.6%). The difference was attributable to a higher incidence of nocturnal sinus pauses in the ticagrelor group. Ventricular pauses ≥3 seconds were less frequent at 1 month of therapy, and there no longer was a significant difference between the ticagrelor (2.1%) and clopidogrel (1.7%) groups. There were no differences between the ticagrelor and clopidogrel groups in the incidence of syncope (0.3% and 0.1%) or pacemaker placement (0.5% and 1.0%).


Ticagrelor predisposes to nocturnal sinus pauses in the acute phase of ACS without increasing the risk of syncope or the need for a pacemaker.


This study was prompted by the unanticipated finding that ticagrelor increased the risk of ventricular pauses in a prior ACS trial (DISPERSE-2). Ticagrelor is known to increase adenosine concentrations by interfering with adenosine metabolism, and this probably explains the higher incidence of nocturnal pauses in the setting of ischemia. The findings suggest that ticagrelor should be used with caution in patients with sick sinus syndrome.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Implantable Devices, EP Basic Science

Keywords: Acute Coronary Syndrome, Follow-Up Studies, Platelet Aggregation Inhibitors, Sick Sinus Syndrome, Syncope, Ticlopidine, Organoplatinum Compounds, Bradycardia

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