Results of the PLATO trial suggest the antiplatelet therapy ticagrelor is superior to clopidogrel in patients with acute coronary syndromes, with or without ST-segment elevation.
Ticagrelor significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in major bleeding.
Investigators published the results of the study in The New England Journal of Medicine.
Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12. It has a faster onset and greater platelet inhibition than clopidogrel, which also blocks the adenosine diphosphate receptor P2Y12, but irreversibly.
Lars Wallentin, MD, PhD, of Uppsala Clinical Research Center in Sweden, and his colleagues set out to ascertain whether ticagrelor is superior to clopidogrel for the prevention of vascular events and death.
They enrolled 18,624 patients from 862 centers in 43 countries from October 2006 through July 2008. They randomized the patients to receive 90 mg of ticagrelor twice daily after a loading dose of 180 mg, or 75 mg of clopidogrel after a 300 mg loading dose. Patients in both cohorts took 75-100 mg aspirin daily.
Baseline patient characteristics were similar in the 2 groups.
After a 12-month follow-up, investigators determined that patients in the ticagrelor group experienced significantly fewer deaths from vascular causes, myocardial infarction, or stroke (9.8%) than those in the clopidogrel group (11.7%; P<0.001). And the treatment effect was noticeable within the first 30 days.
Investigators also observed that ticagrelor significantly reduced myocardial infarction alone (5.8% vs 6.9%; P=0.005), death from vascular causes (4.0% vs 5.1%; P=0.001), and death from any cause (4.5% vs 5.9%; P<0.001).
However, ticagrelor did not reduce stroke alone compared to clopidogrel (P=0.22). And patients on tricagrelor experienced more hemorrhagic strokes than those on clopidogrel.
The investigators also determined that ticagrelor did not increase the rate of overall bleeding. However, it did increase the rate of non-procedure-related bleeding.
The investigators noted more dyspnea in the ticagrelor group than the clopidogrel group (14.2% vs 9.2%; P<0.001). The investigators pointed out that few patients dropped out of the study, however, because of dyspnea.
In an accompanying editorial, Albert Schömig, MD, of the Deutsches Herzzentrum München in Germany, emphasized that the absence of increased bleeding with ticagrelor “highlights the important advantage of reversibility in the mechanism of action of ticagrelor.”
Dr Schömig felt that the study would have been stronger, however, if ticagrelor had been administered for at least a year, if the clopidogrel loading dose had been used for all patients in that arm irrespective of whether they had previously been treated with clopidogrel, and if patients had used proton-pump inhibitors less frequently after randomization.
Nevertheless, Dr Schömig concluded that “efforts to develop new effective and safe antithrombotic drug regimens should not be discouraged by the perception that an increase in antithrombotic efficacy is necessarily associated with a higher risk of bleeding.”
The study was supported by AstraZeneca, the company developing ticagrelor. The drug is not yet on the market.
