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Joint utilisation of medications to block platelets optimally - JUMBO-TIMI 26
Description:
The goal of the trial was to evaluate the safety of the novel thienopyridine P2Y12 antagonist prasugrel compared with clopidogrel among patients undergoing elective or urgent percutaneous coronary intervention (PCI) with intended coronary stenting.
Study Design
Study Design:
Patients Enrolled: 904
Mean Follow Up: 30 days
Mean Patient Age: Median age 59 years
Female: 23
Patient Populations:
Age 18-75 years, candidate for elective or urgent PCI with intended coronary stenting, and a native target coronary artery stenosis >60% by visual estimation amenable to stenting with ≥2 stents
Exclusions:
Planned PCI procedure as initial treatment for an ST elevation MI (STEMI) or within 24 hours of fibrinolytic therapy for STEMI, left main stenosis ≥50% not protected by at least one patent bypass graft, left ventricular ejection fraction <30% or New York Heart Association class III or IV congestive heart failure or cardiogenic shock, increased bleeding risks, stroke within two years, uncontrolled hypertension, or treatment with a thienopyridine within five days
Primary Endpoints:
Significant non-CABG bleeding (TIMI major or minor bleeding) at 30 days
Secondary Endpoints:
MACE at 30 days, defined as death, MI, cardiac target vessel thrombosis, stroke, or rehospitalization for recurrent ischemia
Drug/Procedures Used:
Patients were randomized to clopidogrel (300 mg loading dose and 75 mg/day maintenance dose for 30 days; n=250) or one of three doses of prasugrel: 40 mg loading dose plus 7.5 mg maintenance dose (n=200); 60 mg loading dose plus 10 mg maintenance dose (n=200); or 60 mg loading dose plus 15 mg maintenance dose (n=250). Glycoprotein IIb/IIIa inhibitor use was at the discretion of the investigator.
Concomitant Medications:
Aspirin 325 mg
Principal Findings:
The primary endpoint of significant non-CABG bleeding at 30 days occurred in 1.7% of patients in the pooled prasugrel group and 1.2% of patients in the clopidogrel group (p=0.77), with rates of 1.5% in low-dose prasugrel, 2.0% in intermediate dose prasugrel, and 1.6% in high dose prasugrel. Any bleeding, including TIMI major, minor, and minimal bleeding, trended higher in the high dose prasugrel group compared with the low and intermediate dose group, but there was no difference between the pooled prasugrel group compared with clopidogrel (4.2% vs. 3.5%, p=0.685).
The secondary endpoint of major adverse cardiac events (MACE) at 30 days occurred in 7.2% of patients in the pooled prasugrel group and 9.4% of patients in the clopidogrel group (hazard ratio [HR] 0.76, p=0.26), with rates of 7.5% in low dose prasugrel, 7.5% in intermediate dose prasugrel, and 6.8% in high dose prasugrel.
Myocardial infarction (MI) occurred in 5.7% of patients in the pooled prasugrel group and 7.9% of patients in the clopidogrel group (HR 0.72, p=0.23), with rates of 7.0%, 6.5%, and 4.0% in the low, intermediate, and high doses, respectively. Target vessel thrombosis occurred less frequently in the pooled prasugrel group (0.6% vs. 2.4%, p=0.024), with a dose ranging response (1.0% for low dose prasugrel, 0.5% for intermediate dose, and 0.4% for high dose prasugrel). Severe recurrent ischemia trended lower in the pooled prasugrel group (1.7% vs. 3.5%, HR 0.47, p=0.086).
Interpretation:
Among patients undergoing elective or urgent PCI with intended coronary stenting, treatment with the novel thienopyridine prasugrel was not associated with a difference in the rate of the primary endpoint of significant non-CABG bleeding compared with clopidogrel. The trial was designed to evaluate the safety of this novel thienopyridine, but despite being underpowered, there were consistent but nonsignificant trends toward lower ischemic event rates. Clopidogrel resistance has been associated with increased ischemic events, a population that may potentially benefit from prasugrel.
The upcoming 13,000-patient TRITON-TIMI 38 trial will evaluate the efficacy of prasugrel compared with clopidogrel on the composite endpoint of death, MI, or stroke in acute coronary syndrome patients with PCI.
References:
Wiviott SD, et al. Randomized Comparison of Prasugrel (CS-747, LY640315), a Novel Thienopyridine P2Y12 Antagonist, With Clopidogrel in Percutaneous Coronary Intervention. Circulation. 2005;111:3366-3373.
Wiviott SD. JUMBO-TIMI 26: Joint utilisation of medications to block platelets optimally. Paper presented at the European Society of Cardiology Congress 2004, 29 August-1 September, Munich, Germany.
Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Thiophenes, Ticlopidine, Piperazines, Polyethylene Glycols, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Stents, Coronary Stenosis, Thrombosis, Research Personnel
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