Many treatments have been identified that confer robust cardioprotection in experimental
animal models of acute ischemia and reperfusion injury. However, translation of these
cardioprotective therapies into the clinical setting of acute myocardial infarction
(AMI) for patient benefit has been disappointing. One important reason might be that
AMI is multifactorial, causing cardiomyocyte death via multiple mechanisms, as well
as affecting other cell types, including platelets, fibroblasts, endothelial and smooth
muscle cells, and immune cells. Many cardioprotective strategies act through common
end-effectors and may be suboptimal in patients with comorbidities. In this regard,
emerging data suggest that optimal cardioprotection may require the combination of
additive or synergistic multitarget therapies. This review will present an overview
of the state of cardioprotection today and provide a roadmap for how we might progress
towards successful clinical use of cardioprotective therapies following AMI, focusing
on the rational combination of judiciously selected, multitarget therapies. This paper
emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation
in Science and Technology (COST) Action, CA16225.
