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PLATO: Ticagrelor an effective alternative to clopidogrel for ACS

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ESC Congress 2009

Ticagrelor, an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor (P2Y12), significantly reduced rates of death from vascular causes, MI or stroke compared with clopidogrel. In addition, the drug did not increase overall major bleeding risks, according to the results of the PLATO trial.

PLATO included 18,624 patients admitted to the hospital with acute coronary syndromes (with or without ST-segment elevation).

Lars C. Wallentin, MD, Uppsala Clinical Research Center, Uppsala, Sweden, noted on Sunday during a presentation at the European Society of Cardiology 2009 Annual Meeting that although guidelines recommend dual antiplatelet therapy with aspirin and clopidogrel for acute coronary syndromes, patient response to clopidogrel can vary, and bleeding risks are increased in patients with acute coronary syndromes who are undergoing percutaneous coronary interventions.

Patients included in the multicenter, double blind, PLATO trial were randomly assigned a 180 mg loading dose and 90 mg twice-daily maintenance dose of ticagrelor (Brilinta, AstraZeneca; n=9,333), or a 300 mg to 600 mg loading dose and 75 mg daily dose of clopidogrel (n=9,291).

The primary endpoint was a composite of death from vascular causes, MI or stroke.

At 12 months, the primary composite endpoint occurred less often in the ticagrelor group than in the clopidogrel group (9.8% vs. 11.7%; P<0.001). This treatment effect appeared within 30 days and was maintained throughout the study period.

Secondary endpoints favoring ticagrelor included incidence of MI (5.8% vs. 6.9%; P=0.005), death from vascular causes (4% vs. 5.1%, P=0.001) and death from any cause (4.5% vs. 5%, P<0.001).

Major bleeding was similar between treatment groups (11.6% vs. 11.2%; P=0.43). Major bleeding not related to CABG was higher with ticagrelor (4.5% vs. 3.8%; P=0.03), with more fatal intracranial bleeding but less bleeding of other types. Dyspnea was more common in patients assigned ticagrelor, leading to discontinuation of treatment in 0.9% of patients compared with 0.1% assigned clopidogrel (P<0.001).

“Replacing clopidogrel with ticagrelor in 1,000 patients admitted to hospitals for acute coronary syndrome [for] 12 months treatment would lead to 14 fewer deaths, 11 fewer MIs and six to eight fewer cases of stent thrombosis, without increasing the need for transfusions,” Wallentin said. “Ticagrelor is a more effective alternative [to] clopidogrel for the continuous prevention of ischemic events, stent thrombosis and death in the acute and long-term treatment of patients with ACS.” – Walter Alexander

For more information:

• Wallentin LC. Presented at: ESC Congress 2009; Aug. 29-Sept. 2, 2009; Barcelona.