Evaluation of Ticagrelor Anti Platelet and Pleiotropic Effects in Patients Undergoing Percutaneous Coronary Intervention for an Acute Coronary Syndrome
Condition: Acute Coronary Syndrome
MeSH terms: Acute Coronary Syndrome; Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      Ticagrelor is a new P2Y12 ADP receptor antagonist. This drug demonstrated a faster onset of
      action and a higher potency compared to clopidogrel standard regimen. Consistently these
      properties were associated in the PLATO trial, and particularly in the percutaneous coronary
      intervention (PCI) arm of the study, with a lower incidence of thrombotic complications at
      one year follow-up but at a price of increased major bleedings (7,8). The major finding of
      the trial was a significant reduction in one year mortality in patients treated with
      ticagrelor. This reduction in mortality may not be related to the anti-platelet effect of the
      drug since another potent anti-platelet agent which was recently commercialized a did not
      exhibit any improvement in death compared to clopidogrel. Therefore there may be non anti
      platelet directed properties, or pleiotropic effects, of ticagrelor that could be involved in
      a reduction in mortality in acute coronary syndrome (ACS) patients. In fact together with its
      anti platelet properties, ticagrelor, has been shown to inhibit the uptake of adenosine by
      red cells, leading to an increase in adenosine plasma level and then activating the low
      affinity adenosine receptor thus potentially affecting the vascular homeostasis including
      endothelial cells. Therefore, it is hypothesis that the side effects and its benefit on
      mortality may be related to its interaction with adenosine metabolism. In line with this
      hypothesis, some adverse effects of ticagrelor (bradycardia and modulation of
      bronchoconstriction) are compatible with the activation of low affinity A1 or A2A adenosine
      receptors.

      In addition the investigators have recently demonstrated that P2Y12 ADP blockade did impact
      the endothelial compartment during PCI (9). In fact the investigators have observed that the
      level of PR inhibition achieved by clopidogrel before PCI correlated with the extent of
      endothelial damage during PCI. More potent anti platelet drugs such as ticagrelor may thus be
      associated with reduced peri-procedural endothelial lesion which could further improve the
      clinical prognosis of patients. The investigators have previously observed that endothelial
      marker of lesion and regeneration could be measured in the blood post PCI (10).

      Finally, in the response trial no patients in the ticagrelor arm had HTPR compared to 50% in
      the clopidogrel arm (7). This finding is surprising since recent data suggest that some
      patients still exhibit HTPR following the use of the very potent third generation
      thienopyridine prasugrel. This may be related to the fact that in the response trial only
      stable patients were included.

      The investigators aimed to evaluate the anti-platelet efficacy and pleiotropic effects of
      ticagrelor in acute coronary syndromes patients undergoing percutaneous coronary
      intervention.
    


Intervention name(s): Clopidogrel; trigagrelor
Intervention type(s): Drug; Drug
Intervention description(s): 600mg loading dose then 75mg/day; 180 mg loading dose then 90 mg Twice a day
Intervention MeSH terms: Clopidogrel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment