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Individualised Antiplatelet Therapy


Table 3: Studies Evaluating the Merit of Changing Therapy Based on Platelet Reactivity Study


Design and GRAVITAS107


Estimated Accrual (n) Design:


Treatment, randomised, double-blind, placebo- controlled, parallel assignment, safety/ efficacy study


Estimated accrual: ACS–PCI–DES (2,783)


ARCTIC108 Design:


Treatment, randomised, open-label, active control, parallel assignment, safety/efficacy study


Estimated accrual: Elective PCI–DES (2,500)


Second randomisation after one year of follow-up: C: Pursuit arm: Pursuit of a dual oral antiplatelet therapy (aspirin and clopidogrel) beyond one year. D: Interruption arm: Interruption of clopidogrel therapy.


DANTE109 Design:


Treatment, randomised, open-label, active control, parallel assignment,


efficacy study Estimated accrual:


TOPAS-1110


Unstable or NSTEMI–PCI (442) Design:


A: Active comparator:


Screening, non-randomised, Patients with previously experienced ST while on dual antiplatelet open-label, active control, parallel assignment,


treatment within 6 months after coronary stenting for CAD; clopidogrel 75mg once daily. Patients not already on clopidogrel


pharmacodynamics study Estimated accrual:


Previous PCI or stenting for CAD (450)


treatment will receive a loading dose of clopidogrel 600mg. B: Active comparator:


Patients with previously experienced MI while on dual antiplatelet treatment within 6 months after coronary stenting for CAD;


clopidogrel 75mg once daily. Patients not already on clopidogrel treatment will receive a loading dose of clopidogrel 600mg. C: Active comparator:


TRIGGER-PCI111 Design:


Treatment, randomised, double-blind, active-


Patients without previously experienced MI or ST within 6 months after coronary stenting for CAD (matched controls for group A and B); clopidogrel 75mg once daily. Patients not already on clopidogrel treatment will receive a loading dose of clopidogrel 600mg. A: Experimental (drug: prasugrel):


One-time 60mg oral loading dose and 10mg once-daily oral maintenance dose up to 6 months.


controlled, parallel assignment, B: Active comparator (drug: clopidogrel): safety/efficacy study


Estimated accrual: CAD–DES (2,150)


ACS = acute coronary syndromes; CAD = coronary artery disease; CV = cardiovascular; DES = drug-eluting stent; MACE = major cardiovascular events; MI = myocardial infarction; NSTEMI = non-ST-segment-elevation myocardial infarction; PCI = percutaneous coronary intervention; ST = stent thrombosis; TLVR = target lesion vessel revascularisation.


care platelet function test). A composite end-point of death, MI, stroke, urgent coronary revascularisation and stent thrombosis will be assessed at one-year follow-up.


INTERVENTIONAL CARDIOLOGY Future Perspectives


Studies show point-of-care platelet function tests to be promising for the measurement of patient response to antiplatelet therapy, with the


101 75mg oral daily maintenance dose up to 6 months.


VerifyNow P2Y12 (platelet reactvitiy units).


Time-frame: within 6 months


A: Placebo comparator: standard therapy: Clopidogrel 75mg/day.


B: Active comparator: doubled therapy: Clopidogrel 150mg/day.


6- and 12-month incidence of MACE (CV death, non-fatal MI, TLVR by PCI or coronary bypass).


Treatment Arms A: Active comparator:


‘Tailored’ clopidogrel regimen – clopidogrel 450mg loading dose then clopidogrel 75mg daily for 6 months. B: Placebo comparator:


‘Standard’ clopidogrel regimen – a placebo loading dose and Responders: a random sample of clopidogrel responders treated


with a placebo loading dose and then the standard clopidogrel regimen of 75mg and 1 placebo tablet every day for 6 months. First randomisation: A: Monitoring arm:


Dose adjustment of both aspirin and clopidogrel in suboptimal responders identified based on a point of care assay (VerifyNow). B: Conventional arm:


Fixed-dose regimen of both aspirin and clopidogrel in all patients following DES implantation according to international guidelines.


Composite end-point of death, MI, stroke, ST and urgent coronary


revascularisation assessed at specified time-points (one year in both


‘monitoring’ and ‘conventional’ arms and during the period from 6 up to 18 months in the ‘interruption’ and ‘pursuit’ arms).


Primary Outcome Measure Time to first occurrence of post-


randomisation CV death, non-fatal MI or ARC definite/probable ST in non- responders randomised to standard versus tailored dosage.


then clopidogrel 75mg and 1 placebo tablet every day for 6 months. Time-frame: 6 months. C: Placebo comparator:


Time to first occurrence of heart attack or CV death.


Time-frame: through 6 months.


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