Early Thienopyridine Treatment to Improve Primary PCI in Patients With Acute MI
Condition: Myocardial Infarction; STEMI
MeSH terms: Myocardial Infarction; Infarction
Study type: Interventional
Phase: Phase 3

Summary: 
      Acute myocardial infarction is generally caused by a thrombotic occlusion of coronary
      arteries. Primary aim of early therapy is a fast and complete reperfusion of the infarcted
      myocardium.
    

Detailed description: 
      This could be achieved by either thrombolytic therapy or primary Percutaneous coronary
      intervention (PCI).

      Comparison of the different therapies in randomized trials shows an advantage of primary PCI
      regarding rates of recanalisation of the infarct vessel, preservation of left ventricular
      (LV) function, and reduction in the rate of reinfarctions. In addition, the in-hospital
      mortality is lower in patients undergoing primary PCI. Nevertheless, primary PCI does not
      always result in a successful reperfusion despite of successful restoration of blood flow in
      the epicardial infarct related artery.

      Effective platelet inhibition is a cornerstone of therapy in patients with STEMI. In the
      ISIS-2 study acetylsalicylic acid (ASA) has been shown to improve short- and long-term
      clinical outcome in the same extent as fibrinolysis with streptokinase. Dual platelet
      inhibition with ASA and a thienopyridine has been repeatedly demonstrated to be more
      effective than ASA alone. Clopidogrel on top of ASA improved outcome in patients with acute
      coronary syndromes with and without PCI in the CURE study. Furthermore, a loading dose of 300
      mg clopidogrel was advantageous in elective PCI in the CREDO trial and the addition of
      clopidogrel to ASA improved the patency rate of the infarct related artery in patients with
      STEMI undergoing fibrinolysis. In the BRAVE 3 study, the addition of abciximab to a
      background therapy of a high loading dose of 600 mg clopidogrel plus ASA did not result in an
      additional clinical benefit in terms of prevention of ischemic complications in primary
      elective PCI, suggesting a near optimal platelet inhibition with this treatment in primary
      PCI. The advantage of a 600 mg loading dose seems mainly related to the more rapid onset of
      the full antiplatelet effect within 2-4 hours as compared to 6-8 hours after 300 mg.

      However, in patients with STEMI scheduled for primary PCI an earlier effective inhibition of
      ADP-induced platelet aggregation, preferably within 60-90 min after administration of the
      drug, is needed.

      The new thienopyridine prasugrel has been shown to achieve a more complete and even more
      rapid platelet inhibition compared to clopidogrel. This might be especially important in
      patients with STEMI scheduled for primary PCI. In these patients activation of platelets is
      more pronounced compared to patients undergoing PCI for stable CAD.

      In a small substudy of the TRITON-TIMI 38 trial inhibition of platelet aggregation measured
      with the VASP assay was more effective with prasugrel than with clopidogrel. However, this
      substudy was done predominantly in patients with unstable angina and NSTEMI. In addition,
      none of these patients were treated in the pre-hospital phase. Therefore it is necessary to
      determine if in patients with acute STEMI an early administration of a high loading dose of
      prasugrel in comparison with clopidogrel before planned primary PCI improves the inhibition
      of platelet aggregation, therefore facilitates this procedure and results in an improved
      myocardial reperfusion before and after PCI.
    

Intervention name(s): Prasugrel; Clopidogrel
Intervention type(s): Drug; Drug
Intervention description(s): treatment with a 60 mg loading dose prasugrel, followed by a maintenance dose of 10 mg for 30 days; treatment with a 600 mg loading dose clopidogrel, followed by a maintenance dose of 75 mg for 30 days
Other intervention name(s): Effient; Efient; Plavix
Intervention MeSH terms: Clopidogrel; Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: STEMI; clopidogrel; prasugrel; platelet reactivity index; ST resolution