TRITON-TIMI 38 was a head-to-head study comparing Prasugrel ( 60-mg loading dose [LD], followed by a 10-mg once-daily maintenance dose ) plus Aspirin ( ASA; Acetylsalicylic acid ) with Clopidogrel ( 300-mg LD, followed by a 75-mg once-daily maintenance dose ) plus ASA in 13,608 patients with acute coronary syndrome ( ACS ) managed with percutaneous coronary intervention ( PCI ), a procedure to open blockages in heart arteries, including the use of coronary stenting.
The median duration of study treatment was 14.5 months.
The primary endpoint of the study was the combined incidence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke in patients followed for 6-15 months following PCI. The study showed that Prasugrel taken with Aspirin had a 19% relative risk reduction of the combined endpoint of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke versus Clopidogrel taken with Aspirin ( 9.9% vs 12.1% respectively, p less than 0.001 ). This corresponds to a 2.2% absolute risk reduction for acute coronary syndrome patients treated with Prasugrel.
In TRITON-TIMI 38, patients treated with Prasugrel also experienced a 50% relative risk reduction ( corresponding to 1.1% absolute risk reduction ) in stent-related clots when compared with Clopidogrel, regardless of stent type ( 1.1% vs 2.4% respectively, p less than 0.001 ).
In TRITON, the risk of non-coronary artery bypass graft ( non-CABG ) major bleeding, including fatal bleeding, was higher with Prasugrel ( 2.4% incidence ) compared with Clopidogrel ( 1.8% incidence ) ( p=0.03 ).
The rate of TIMI major or minor bleeding was significantly greater with Prasugrel than Clopidogrel ( 5.0% vs 3.8% respectively, p=0.002 ).
The risk of coronary artery bypass graft ( CABG ) major bleeding, including fatal bleeding, was higher with Prasugrel ( 13.4% incidence ) than Clopidogrel ( 3.2% incidence ) ( p less than 0.001 ).
Compared with the overall study population, a higher risk of serious bleeding among Prasugrel patients was most evident in three distinct patient populations that are readily identifiable: patients who weighed less than 60 kg, patients who were 75 years of age or older and patients who have had a prior transient ischemic attack ( TIA ) or stroke.
A 5 mg maintenance dose should be used for patients who weigh less than 60 kg.
Prasugrel is generally not recommended for use in patients 75 years or older. If, after a careful individual benefit/risk evaluation by the prescribing physician treatment is deemed necessary a 5 mg maintenance dose should be prescribed. Patients with prior TIA or stroke should not be treated with Prasugrel.
In this study, survival analysis methods were used to compare outcomes by treatment assignment ( Prasugrel vs Clopidogrel ) and to compare outcomes by whether subjects were included in the core clinical cohort, non-core cohort or contraindicated cohort.
The principal limitation of this analysis is that the subgroups examined were identified in a post-hoc fashion.
Source: Eli Lilly, 2011