PLATO: Ticagrelor an effective alternative to clopidogrel for ACS

European Society of Cardiology 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 the PLATO trial.

Ticagrelor (Brilinta, AstraZeneca) also did not increase overall major bleeding risks. PLATO included 18,624 patients admitted to the hospital with ACS (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 while guidelines recommend dual antiplatelet therapy with aspirin and clopidogrel (Plavix, Sanofi Aventis) for ACS, clopidogrel responses can be variable, and bleeding risks are increased in ACS patients undergoing percutaneous coronary interventions.

The 18,624 patients included in the multicenter, double-blind, randomized PLATO trial were assigned by researchers to a 180-mg loading dose and 90 mg twice-daily maintenance dose of Ticagrelor (n=9,333) or a 300-600 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 was significantly less often in the ticagrelor group than in the clopidogrel group (9.8% vs. 11.7%; 95% CI 0.77-0.92; P<0.001). This treatment effect appeared within 30 days and was maintained throughout the study period. Secondary endpoints favoring ticagrelor included MI (5.8% ticagrelor, 6.9% clopidogrel; P=0.005), death from vascular causes (4% ticagrelor vs. 5.1% clopidogrel, P=0.001) and death from any cause (4.5% ticagrelor vs. 5% clopidogrel, P<0.001).

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

“Replacing clopidogrel with ticagrelor in 1,000 patients admitted to hospitals for ACS [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.”

ESC discussant Steen D. Kristensen, MD, of Aarhus University, Skejby, Denmark, called ticagrelor “a promising drug” that might, because of its reversibility, make it easier to manage patients on antiplatelet therapy undergoing surgery. — Walter Alexander

Wallentin LC. #179. Presented at: European Society of Cardiology Congress 2009; Aug. 29-Sept. 2, 2009; Barcelona