Concomitant Milrinone and Esmolol Treatment in Patients with Acute Myocardial Infarction

Summary

Heart attack is the leading cause of death in the developed world. Following heart attack, re-establishing blood flow in a clogged heart vessel using percutaneous coronary intervention (PCI) is the standard of care. This therapy is called reperfusion therapy. Unfortunately, reperfusion therapy itself poses additional heart muscle damaging effect, a process called reperfusion injury. Excessive reperfusion injury can offset the net benefit of heart vessel blood flow restoration in patients with heart attacks. For those heart attack survivors, massive reperfusion injury can contribute to heart failure which carries high risk for death and long-term disabilities. To date, there is no drug available that can reduce reperfusion injury in heart attack patients. Our group has demonstrated in a preclinical study that combining two available medications (milrinone and esmolol) when given right before the onset of reperfusion therapy greatly reduces heart muscle damage in an animal heart attack model. Furthermore, in a clinical safety, we demonstrated that combination therapy with milrinone and esmolol is safe in patients with heart attack undergoing PCI. If the heart-protective effect observed in our preclinical study can be replicated in human subjects, this proposed therapy will become the first of this kind to treat clinical reperfusion injury. The present trial is a proof-of-concept study to determine whether the combination administration of milrinone and esmolol at the onset of reperfusion reduces the heart muscle damage in heart attack patients who receive reperfusion therapy with PCI.

Timeline

Start

2015-05

Primary completion

2023-03

Completion

2024-12

Publications

• Background Huang MH, Wu Y, Nguyen V, Rastogi S, McConnell BK, Wijaya C, Uretsky BF, Poh KK, Tan HC, Fujise K. Heart protection by combination therapy with esmolol and milrinone at late-ischemia and early reperfusion. Cardiovasc Drugs Ther. 2011 Jun;25(3):223-32. doi: 10.1007/s10557-011-6302-z.
• Background Poh KK, Xu X, Chan MY, Lee CH, Tay EL, Low AF, Chan KH, Sia W, Tang LQ, Tan HC, Lui CY, Nguyen V, Fujise K, Huang MH. Safety of combination therapy with milrinone and esmolol for heart protection during percutaneous coronary intervention in acute myocardial infarction. Eur J Clin Pharmacol. 2014 May;70(5):527-30. doi: 10.1007/s00228-014-1650-9. Epub 2014 Jan 25.

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