New Drugs Antiplatelets-Antithrombotics - John Fanikos, RPh, MBA ...

Total major bleedingK-M estimated rate (% per year)13121110987654321011.6NS11.2PLATO majorbleeding7.9NS7.7TIMI majorbleedingNS8.9 8.9Red celltransfusion *NS5.8 5.8PLATO lifethreatening/fatal bleedingTicagrelorClopidogrelNS0.3 0.3Fatal bleedingMajor bleeding and major or minor bleeding according to TIMI criteria refer to non-adjudicated events analysed with the useof a statistically programmed analysis in accordance with definition described in Wiviott SD et al. NEJM 2007;357:2001–15;* Proportion of patients (%); NS = not significantSubjectsSubjects who require PCI (with or without stent)1:1 randomization to main treatment groupsDouble blind, double dummyPlacebocapsules(to match)IndexProcedureEndpoints+Cangrelorbolus (30 µg/kg) &infusion (4 µg/kg/min)Clopidogrelcapsules(600 mg)Subjects who require PCIStudy drug infusion: for at least 2 hours or the durationof the procedure, whichever is longerClopidogrel capsules(600 mg)Placebo capsules(to match)Clopidogrel maintenance (at the discretion of the physician)+Placebobolus & infusion(to match)At 48 hours after randomization—• 1° efficacy endpoint: composite incidence of all-cause mortality, MI, and IDR• 2° efficacy endpoint: incidence of individual components, stroke & abrupt vessel closure• Safety endpoints: hemorrhage and transfusion• Safety: AEs/SAEsPrimary Endpoint:48-hour Death/MI/IDR (MITT)7.5%INNOVATE-PCI: Phase II TrialNon-Urgent PCI18-75 Years7.1%P = 0.59RRRClopidogrel 300or 600 mg Load,then 75 mg DailyElinogrel 80 mgIV then 50 mg,Oral Twice Daily60 DaysElinogrel 80 mgIV then 100 mg,Oral Twice DailyElinogrel 80 mgIV then 150 mg,Oral Twice DailyCangrelor: 3897 3623 3619 3619 3614 3606 3604 3603 3599Clopidogrel: 3871 3607 3606 3606 3602 3599 3598 3595 35881. Platelet activity2. Efficacy3.Safety4.TolerabilitySantilli F, Dabi G. Thromb Haemost 2009;101:220-221.