Ticagrelor outdoes clopidogrel in ACS management
Upstream use of the P2Y12 receptor antagonist ticagrelor provides benefit over clopidogrel in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) with a relatively rapid time to angiography, according to a post hoc analysis of the PLATO* trial.
“[Our findings suggest that] the clinical benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography in patients with NSTE-ACS,” said the researchers. “[However], it is possible that the duration of therapy prior to angiography influences the efficacy of upstream therapy.”
Researchers evaluated 6,792 patients with unstable angina/NSTE myocardial infarction (NSTEMI) who have undergone angiography within 72 hours of randomization. Of these, 3,486 underwent early angiography (<3 hours) while 3,306 had late angiography (≥3 hours). Participants were randomized to receive ticagrelor 180 mg loading dose followed by 90 mg twice daily (n=3,446) or clopidogrel 300–600 mg loading dose followed by 75 mg once daily (n=3,346). [Clin Cardiol 2017;40:390-398]
Compared with clopidogrel, ticagrelor reduced the overall risk of cardiovascular death, myocardial infarction, and/or stroke postangiography (hazard ratio [HR], 0.67; p=0.002 for day 7, HR, 0.81; p=0.042 for day 30, and HR, 0.80; p=0.0045 for 1 year).
Major bleeding rates were lower in patients with early angiography in the ticagrelor vs the clopidogrel arms (HR, 0.79 at day 7, HR, 0.88 at day 30, and HR, 0.88 at 1 year).
However, bleeding rates increased in those with late angiography in the ticagrelor vs the clopidogrel arms (HR, 1.51; pinteraction=0.002 at day 7, HR, 1.22; pinteraction=0.037 at day 30, and HR, 1.33, pinteraction=0.003 at 1 year), consistent with previous analyses which also showed increased bleeding events with ticagrelor during late angiography. [Am J Emerg Med 2013;31:1005-1011; EuroIntervention 2015;11:737-745]
“These findings are not surprising, as the level of platelet inhibition is higher with the more potent agent, and thus a higher risk of bleeding would be expected over a long period of treatment,” said the researchers.
The higher bleeding risk is a downside of upstream P2Y12 inhibition especially in cases requiring coronary artery bypass grafting, they added, citing a previous trial showing an increased bleeding risk with upstream therapy with the irreversible thienopyridine, prasugrel. [J Am Coll Cardiol 2014;64:2563-2571]
“The underlying concept behind upstream oral antiplatelet therapy with P2Y12 antagonists is that these agents require time to be absorbed after dosing and then exert their effects on plaque instability and thrombus formation,” said the researchers.
Overall, the results support the upstream approach using the more potent and rapid-onset ticagrelor in early invasive management, noted the researchers. “[O]ur results with ticagrelor help to build the case that this reversible agent can play an important role in the upstream management of patients with ACS.”
Furthermore, the results are consistent with the most recent American College of Cardiology and American Heart Association NSTEMI guidelines favouring ticagrelor over clopidogrel in patients who “undergo an early invasive or ischaemia-guided strategy”, noted the researchers.