NEW YORK (Reuters Health) – Ventricular pauses associated with the use of ticagrelor don’t result in clinically significant bradycardia, according to a report in the May 10th Journal of the American College of Cardiology.
“These results offer important, and reassuring, safety data for ticagrelor in terms of the risk of clinically significant bradycardic among patients presenting with acute coronary syndrome (ACS),” Dr. Benjamin M. Scirica from Brigham and Women’s Hospital, Boston, Massachusetts told Reuters Health in an email.
“It is important to remember that patients with significant cardiac conduction disorders who did not have a pacemaker were excluded from the PLATO trial, so these results could not be generalized to those patients.”
Dr. Scirica and colleagues in the Platelet Inhibition and Patient Outcomes (PLATO) trial investigated whether ticagrelor increases the risk of ventricular pauses and whether these pauses were associated with any clinical bradycardic events.
The study included 1472 patients randomized to ticagrelor and 1436 patients randomized to clopidogrel, 964 and 985 of which, respectively, had continuous ECG monitoring for approximately 6 days both during week 1 and at 1 month after randomization.
“The objective of the continuous ECG assessment was to evaluate rigorously whether ticagrelor does in fact result in electrocardiographic captured slowing of the conduction system and whether these bradycardic events have any clinical significance,” Dr. Scirica said.
During the first week, ventricular pauses of at least 3 seconds occurred significantly more frequently in patients assigned to ticagrelor (5.8%) than in patients assigned to clopidogrel (3.6%). By 1 month after randomization, ventricular pauses occurred at less than one-half the rates at week 1 but remained numerically more common in the ticagrelor group.
Among the patients with paired recordings, the pattern was similar: more ticagrelor patients had ventricular pauses, in particular sinoatrial node pauses, compared with clopidogrel patients.
The rates of clinical bradycardic events were far lower than the rates of ventricular pauses. Five ticagrelor patients (0.3%) and 2 clopidogrel patients (0.1%) experienced syncope; 6 ticagrelor patients (0.4%) and 15 clopidogrel patients (1.0%) developed heart block; and 7 ticagrelor patients (0.5%) and 14 clopidogrel patients (1.0%) required pacemaker placement.
Although a few more patients had asymptomatic bradycardia or bradyarrhythmias on ticagrelor than on clopidogrel, the numbers of patients with symptomatic adverse events on the same day as the ventricular pauses didn’t differ between the treatments.
The risk for supraventricular or ventricular tachyarrhythmias didn’t differ between the ticagrelor and clopidogrel groups, and total mortality over the duration of the trial was significantly lower in the ticagrelor group (2.4%) than in the clopidogrel group (3.9%).
“The demonstration that ticagrelor does have physiologic action on the electrical conduction system furthers the knowledge regarding the potential ‘off-target’ action of ticagrelor, which is an important avenue of future research,” Dr. Scirica said. “The overall safety in terms of a lack of any excess in clinical bradycardic events with ticagrelor offers important safety data as ticagrelor is incorporated into clinical practice.”
This study, along with the PLATO trial, was supported by AstraZeneca, manufacturer of ticagrelor. Twelve of the 14 authors of this report indicated some financial relationship with AstraZeneca, including 2 authors who are employed by the company.
The EU’s European Medicines Agency approved ticagrelor for marketing in December 2010.
Although an FDA advisory panel recommended approval for ticagrelor last July, the FDA has delayed approval of the drug while awaiting further analysis of clinical trial data.
J Am Coll Cardiol 2011
