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
