Ticagrelor and Intracoronary Morphine in Patients Undergoing Primary Percutaneous Coronary Intervention

• Myocardial salvage index measured by magnetic resonance imaging (MRI) at 3-5 days after the index procedure [ Time Frame: Post-PCI 3-5 days ] [ Designated as safety issue: No ]
  

• Rate of complete ST-segment resolution on ECG obtained 30 minutes after the procedure [ Time Frame: 30 min after completion of PCI ] [ Designated as safety issue: No ]
  
• Enzymatic Infarct size by creatine kinase-MB (area under curve) [ Time Frame: 1 month later ] [ Designated as safety issue: No ]
  
• Myocardial infarct size measured by MRI [ Time Frame: Post-PCI 3-5 days ] [ Designated as safety issue: No ]
  
• Major adverse cardiac events (a composite of death, myocardial infarction, severe heart failure, or stent thrombosis) [ Time Frame: 1Month later ] [ Designated as safety issue: Yes ]
  
• The extent of microvascular obstruction measured by MRI [ Time Frame: post-PCI 3-5days ] [ Designated as safety issue: No ]
  
• The number of segments with >75% of infarct transmurality measured by MRI [ Time Frame: post-PCI 3-5 days ] [ Designated as safety issue: No ]
  
• The presence of myocardial hemorrhage measured by MRI [ Time Frame: post-PCI 3-5 days ] [ Designated as safety issue: No ]
  

1.1. Ticagrelor versus Clopidogrel

1. In spite of timely and successful reperfusion with primary percutaneous coronary intervention (PCI), the mortality rate still remains high1 and substantial numbers of patients suffer from subsequent left ventricular dysfunction or heart failure after ST-segment elevation myocardial infarction (STEMI).
2. One of limitations of primary PCI is distal embolization and effective antiplatelet therapy is needed in patients with STEMI.
3. Clopidogrel is a representative P2Y12 receptor antagonist and has shown consistent efficacy in patients with acute coronary syndromes. However, clopidogrel is a prodrug and has to be converted to an active metabolite to inhibit P2Y12 receptor. Therefore, onset of effect is relatively slow, antiplatelet effect is moderate, and response to clopidogrel shows wide individual variability.
4. Ticagrelor is a new, direct, reversible P2Y12 receptor antagonist, which has rapid and potent antiplatelet effect. In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding.
5. However, there has been no data whether ticagrelor can reduce infarct size compared with clopidogrel in patients undergoing primary PCI.

1.2. Intracoronary morphine administration

1. Lethal reperfusion injury accounts for up to 50% of the final size of a myocardial infarct.5,6 Therefore, adjunctive therapy that is effective in preventing lethal reperfusion injury is needed to potentiate the benefits of primary PCI.
2. During the past few decades, a large number of animal studies demonstrated that commonly used opioids could provide cardioprotection against ischemia-reperfusion injury. Opioid-induced preconditioning or postconditioning mimics ischemic preconditioning or ischemic postconditioning.
3. Recent small clinical trial demonstrated the cardioprotective effect of remote ischemic preconditioning and morphine during primary PCI. But this study was small and did not demonstrate the separate effect of morphine-induced cardioprotection.

2. Study Objective

1. To investigate the effects of ticagrelor on myocardial salvage in patients with STEMI undergoing primary PCI compared with clopidogrel
2. To investigate the effects of morphine-induced cardioprotection during primary PCI in patients with STEMI