Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38).
BACKGROUND
Dual antiplatelet therapy with aspirin and clopidogrel is standard for prevention of thrombotic complications of percutaneous coronary intervention (PCI). Prasugrel is a thienopyridine that is more potent, more rapid in onset, and more consistent in inhibition of platelets than clopidogrel. TRITON-TIMI 38 is designed to compare prasugrel with clopidogrel in moderate to high-risk patients with acute coronary syndrome (ACS).


METHODS
TRITON-TIMI 38 is a phase 3, randomized, double-blind, parallel-group, multinational, clinical trial. Approximately 13,000 patients with moderate to high-risk ACS undergoing PCI (9500 unstable angina/non-ST-segment elevation myocardial infarction [MI], 3500 ST-segment elevation MI) will be randomized to prasugrel 60 mg loading dose followed by 10 mg daily or clopidogrel 300 mg loading dose followed by 75 mg daily for up to 15 months. The primary end point is the time of the first event of cardiovascular death, MI, or stroke. Analyses will be performed first in the unstable angina/non-ST-segment elevation MI cohort and, conditionally, on the whole ACS population. Major safety end points include TIMI major and minor bleeding unrelated to coronary artery bypass graft surgery.


CONCLUSIONS
TRITON-TIMI 38 is a phase 3 comparison of prasugrel versus clopidogrel in patients with moderate to high-risk ACS undergoing PCI. In addition, it is the first large-scale clinical events trial to assess whether a thienopyridine regimen that achieves a higher level of inhibition of platelet aggregation than the standard therapy results in an improvement in clinical outcomes.
Wiviott
Stephen D
SD
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. swiviott@partners.org
Antman
Elliott M
EM
Gibson
C Michael
CM
Montalescot
Gilles
G
Riesmeyer
Jeffrey
J
Weerakkody
Govinda
G
Winters
Kenneth J
KJ
Warmke
Jeffrey W
JW
McCabe
Carolyn H
CH
Braunwald
Eugene
E
D000208:Acute Disease; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy* / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D012107:Research Design; D013577:Syndrome; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine