Current State of Clinical Translation of Cardioprotective Agents for Acute Myocardial Infarction

Abstract

Abstract:There is continued interest in the concept of limiting myocardial infarct size with adjunctive agents administered along with reperfusion injury; however, there remains considerable controversy in the literature. The purpose of this article is to review the medical literature on clinical trials performed during the past 3 years that have attempted to reduce myocardial infarct size by administration of adjunctive therapies along with reperfusion therapy. A PubMed-driven literature search revealed a host of clinical trials focusing on the following prominent types of therapies: endogenous conditioning (postconditioning and remote ischemic conditioning); rapid cooling; pharmacological therapy (cyclosporine, abciximab, clopidogrel, tirofiban, erythropoietin, thrombus aspiration, adenosine, glucose-insulin-potassium, statins, antidiabetic agents, FX06, iron chelation, and ranolazine). Although there remains some controversy, quite a few of these studies showed that adjunctive therapy further reduced myocardial infarct size when coupled with reperfusion. Antiplatelet agents are emerging as some of the newest agents that seem to have cardioprotective capabilities. Postconditioning has become a bit more controversial in the clinical literature; remote conditioning, early and rapid cooling, adenosine, and ranolazine are intriguing therapies deserving of larger studies. Certain agents and maneuvers, such as erythropoietin, protein kinase C δ inhibitors, iron chelation, and intra-aortic balloon counterpulsation, perhaps should be retired. The correct adjunctive therapy administered along with reperfusion has the capability of further reducing myocardial injury during ST-segment-elevation myocardial infarction. ( infarct size reducing agents in clinical trials. Some of these disappointing agents included antibodies that prevent white blood cell adhesion to the endothelium; eniporide, a sodium/hydrogen exchange inhibitor; caldaret, an intracellular calcium-handling modulator; nicorandil, a potassium ATP channel opener/vasodilator; glucose-insulin-potassium (GIK); delcasertib (a protein kinase C δ inhibitor); and erythropoietin. 5 However, some agents and maneuvers that were observed to work in experimental models did show promise in clinical trials of MI under the right circumstances: postconditioning; remote conditioning; cyclosporine (maintains the mitochondrial permeability transition pore closed); intravenous adenosine infusions; atrial natriuretic peptide; mild hypothermia induced before reperfusion; supersaturated oxygen therapy and others. [4][5][6][7] The reasons for discrepancies between experimental findings and clinical trials have been reviewed in detail. 6,7 Since these reviews were written there have been a large number of new clinical trials recently published during the past 3 years, on the basis of literature searches through PubMed. These trials cover additional new studies on therapies, such as conditioning, abciximab, clopidogrel, erythropoietin, hypothermia, thrombectomy, intracoronary adenosine...

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