Ticagrelor versus clopidogrel in patients with acute coronary syndromes.
BACKGROUND
Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel.


METHODS
In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation.


RESULTS
At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types.


CONCLUSIONS
In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding. (ClinicalTrials.gov number, NCT00391872.)
Wallentin
Lars
L
Uppsala Clinical Research Center, Uppsala, Sweden. lars.wallentin@ucr.uu.se
Becker
Richard C
RC
Budaj
Andrzej
A
Cannon
Christopher P
CP
Emanuelsson
Håkan
H
Held
Claes
C
Horrow
Jay
J
Husted
Steen
S
James
Stefan
S
Katus
Hugo
H
Mahaffey
Kenneth W
KW
Scirica
Benjamin M
BM
Skene
Allan
A
Steg
Philippe Gabriel
PG
Storey
Robert F
RF
Harrington
Robert A
RA
Freij
Anneli
A
Thorsén
Mona
M
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000077144:Clopidogrel; D004311:Double-Blind Method; D004417:Dyspnea / Q000139:chemically induced; D004562:Electrocardiography; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D058919:Purinergic P2 Receptor Antagonists; D020521:Stroke / Q000401:mortality; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine