Efient* 5 mg film-coated tablets. Efient 10mg film-coated t(八)
GPIIb/IIIa inhibitors, and stent type. The benefit was primarily due to a significant decrease in non-fatal MI (see Table 3). Subjects with diabetes had significant reductions in the primary, and all secondary composite endpoints.
The observed benefit of prasugrel in patients 75 years was less than that observed in patients <75 years. Patients 75 years were at increased risk of bleeding, including fatal (see sections 4.2, 4.4, and 4.8). Patients 75 years in whom the benefit with prasugrel was more evident included those with diabetes, STEMI, higher risk of stent thrombosis, or recurrent events.
Patients with a history of TIA or a history of ischaemic stroke more than 3 months prior to prasugrel therapy had no reduction in the primary composite endpoint.
Table 3: Patients with Outcome Events in TRITON Primary Analysis
In the All ACS population, analysis of each of the secondary endpoints showed a significant benefit (p<0.001) for prasugrel versus clopidogrel. These included definite or probable stent thrombosis at study end (0.9% vs. 1.8%; HR 0.498; CI 0.364, 0.683); CV death, non-fatal MI, or urgent target vessel revascularisation through 30 days (5.9% vs. 7.4%; HR 0.784; CI 0.688,0.894); all cause death, non-fatal MI, or non-fatal stroke through study end (10.2% vs. 12.1%; HR 0.831; CI 0.751, 0.919); CV death, non-fatal MI, non-fatal stroke or rehospitalisation for cardiac ischaemic event through study end (11.7 % vs. 13.8%; HR 0.838; CI 0.762, 0.921). Analysis of all cause death did not show any significant difference between prasugrel and clopidogrel in the All ACS population (2.76% vs. 2.90%), in the UA/NSTEMI population (2.58% vs. 2.41%), and in the STEMI population (3.28% vs. 4.31%).
Prasugrel was associated with a 50% reduction in stent thrombosis through the 15-month follow-up period. The reduction in stent thrombosis with Efient was observed both early and beyond 30 days for both bare metal and drug eluting stents.
In an analysis of patients who survived an ischaemic event, prasugrel was associated with a reduction in the incidence of subsequent primary endpoint events (7.8% for prasugrel vs. 11.9% for clopidogrel).
Although bleeding was increased with prasugrel, an analysis of the composite endpoint of death from any cause, non-fatal myocardial infarction, non-fatal stroke, and Non-CABG-related TIMI major haemorrhage favoured Efient compared to clopidogrel (Hazard Ratio, 0.87; 95% CI, 0.79 to 0.95; p=0.004). In TRITON, for every 1000 patients treated with Efient, there were 22 fewer patients with myocardial infarction, and 5 more with Non–CABG-related TIMI major haemorrhages, compared with patients treated with clopidogrel.
Results of a pharmacodynamic/pharmacogenomic study in 720 Asian ACS PCI patients demonstrated that higher levels of platelet inhibition are achieved with prasugrel compared to clopidogrel, and that prasugrel 60-mg loading dose/10-mg maintenance dose is an appropriate dose regimen in Asian subjects who weigh at least 60 kg and are less than 75 years of age (see section 4.2).
5.2 Pharmacokinetic properties
Prasugrel is a prodrug and is rapidly metabolised in vivo to an active metabolite and inactive metabolites. The active metabolite's exposure (AUC) has moderate to low between-subject (27%) and within-subject (19%) variability. Prasugrel's pharmacokinetics are similar in healthy subjects, patients with stable atherosclerosis, and patients undergoing percutaneous coronary |
