Efient* 5 mg film-coated tablets. Efient 10mg film-coated t(七)
l 10 mg compared with those treated with clopidogrel 150 mg. No data are available on switching from a clopidogrel loading dose directly to a prasugrel loading dose.
Efficacy and Safety in Acute Coronary Syndrome (ACS)
The phase 3 TRITON study compared Efient (prasugrel) with clopidogrel, both co-administered with ASA and other standard therapy. TRITON was a 13,608 patient, multi-centre international, randomised, double-blind, parallel group study. Patients had ACS with moderate to high risk UA, NSTEMI, or STEMI and were managed with PCI.
Patients with UA/NSTEMI within 72 hours of symptoms or STEMI between 12 hours to 14 days of symptoms were randomised after knowledge of coronary anatomy. Patients with STEMI within 12 hours of symptoms and planned for primary PCI could be randomised without knowledge of coronary anatomy. For all patients, the loading dose could be administered any time between randomisation and 1 hour after the patient left the catheterisation lab.
Patients randomised to receive prasugrel (60 mg loading dose followed by 10 mg once daily) or clopidogrel (300 mg loading dose followed by 75 mg once daily) were treated for a median of 14.5 months (maximum of 15 months with a minimum of 6 months follow-up). Patients also received ASA (75 mg to 325 mg once daily). Use of any thienopyridine within 5 days before enrolment was an exclusion criterion. Other therapies, such as heparin and GPIIb/IIIa inhibitors, were administered at the discretion of the physician. Approximately 40% of patients (in each of the treatment groups) received GPIIb/IIIa inhibitors in support of PCI (no information available regarding the type of GPIIb/IIIa inhibitor used). Approximately 98% of patients (in each of the treatment groups) received antithrombins (heparin, low molecular weight heparin, bivalirudin, or other agent) directly in support of PCI.
The trial's primary outcome measure was the time to first occurrence of cardiovascular (CV) death, non-fatal myocardial infarction (MI), or non-fatal stroke. Analysis of the composite endpoint in the All ACS population (combined UA/NSTEMI and STEMI cohorts) was contingent on showing statistical superiority of prasugrel versus clopidogrel in the UA/NSTEMI cohort (p<0.05).
All ACS population: Efient showed superior efficacy compared to clopidogrel in reducing the primary composite outcome events as well as the pre-specified secondary outcome events, including stent thrombosis (see Table 3). The benefit of prasugrel was apparent within the first 3 days and it persisted to the end of study. The superior efficacy was accompanied by an increase in major bleeding (see sections 4.4 and 4.8). The patient population was 92% Caucasian, 26% female, and 39% 65 years of age. The benefits associated with prasugrel were independent of the use of other acute and long-term cardiovascular therapies, including heparin/low molecular weight heparin, bivalirudin, intravenous GPIIb/IIIa inhibitors, lipid-lowering medicinal products, beta-blockers, and angiotensin converting enzyme inhibitors. The efficacy of prasugrel was independent of the ASA dose (75 mg to 325 mg once daily). The use of oral anticoagulants, non-study antiplatelet medicinal products and chronic NSAIDs was not allowed in TRITON. In the All ACS population, prasugrel was associated with a lower incidence of CV death, non-fatal MI, or non-fatal stroke compared to clopidogrel, regardless of baseline characteristics such as age, sex, body weight, geographical region, use of |
