Ticagrelor associated with lower rate of death from vascular causes, MI, and stroke

In the Study of Platelet Inhibition and Patient Outcomes (PLATO) published in the New England Journal of Medicine, patients with acute coronary syndrome (ACS) who were treated with ticagrelor had significant reductions in the rate of death from vascular causes, myocardial infarction (MI), or stroke, and no significant increase in the rate of overall major bleeding versus patients treated with clopidogrel.

In this multicenter, double-blind, randomized trial, 18,624 patients who were hospitalized for ACS with or without ST-segment elevation with onset of symptoms during the previous 24 hours were randomized to treatment with either ticagrelor or clopidogrel. Ticagrelor was administered as a 180-mg loading dose followed by a 90-mg dose twice/d; clopidogrel was administered as a 300-mg loading dose followed by a 75-mg dose once/d. Patients who underwent percutaneous coronary intervention (PCI) after randomization received an additional loading dose of the study drug at the time of PCI. The primary end point was the time to the first occurrence of the composite of death from vascular causes, MI, or stroke. The principal secondary end point was the occurrence of the primary end point in the subgroup of patients with invasive management planned at randomization.

Both groups began treatment at a median of 11.3 hours after the onset of chest pain. The primary end point occurred in 9.8% of ticagrelor-treated patients and 11.7% of clopidogrel-treated patients at 12 months (HR=0.84; 95% CI, 0.77–0.92; PPP=.0005); and death from vascular causes (P=.001). The secondary end point occurred less frequently in patients treated with ticagrelor (8.9%) than in patients treated with clopidogrel (10.6%; P=.003). There was no significant difference between the ticagrelor and clopidogrel groups in the rate of major bleeding (P=.43); however, ticagrelor-treated patients were more likely to experience non-coronary artery bypass grafting (CABG) major bleeding than clopidogrel-treated patients (4.5% vs 3.8%; P=.03).

The authors pointed out that because P2Y12 inhibition is reversible with ticagrelor, the agent’s antiplatelet effect “dissipates more rapidly than with the thienopyridines, which are irreversible P2Y12 inhibitors.” This reversible P2Y12 inhibition contributes to the lower incidence of procedure-related bleeding with ticagrelor. The authors concluded that “treatment with ticagrelor as compared with clopidogrel in patients with acute coronary syndromes significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke,” and this benefit was achieved without a significant increase in major bleeding.

In a related editorial, Albert Schomig, MD, states that because new side effects, including dyspnea, bradyarrhythmia, and increased uric acid and creatinine levels, were observed with ticagrelor, healthcare professionals should “carefully monitor patients receiving this drug to establish the overall impact of its side effects.” Dr Schomig also suggested that “the whole story concerning the adverse effects of ticagrelor may require evaluation in a much larger number of patients, something that may be beyond the capacity of a randomized trial.”

Wallentin L, Becker RC, Budaj A, et al; for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361.

Schomig A. Ticagrelor-Is there need for a new player in the antiplatelet-therapy field [editorial]? N Engl J Med. 2009;361.