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We review the clinical efficacy of mitoprotective drugs that have progressed to clinical testing comprising cyclosporine A, KAI\u20109803, MTP131 and TRO 40303. Whereas cyclosporine may reduce infarct size in patients undergoing primary angioplasty as evaluated by release of myocardial ischaemic biomarkers and infarct size imaging, the other drugs were not capable of demonstrating this effect in the clinical setting. The absent effect leaves the role of the mitochondrial permeability transition pore for reperfusion injury in humans unanswered and indicates that targeting one single mechanism to provide mitoprotection may not be efficient. Moreover, the lack of effect may relate to favourable outcome with current optimal therapy, but conditions such as age, sex, diabetes, dyslipidaemia and concurrent medications may also alter mitochondrial function. However, as long as the molecular structure of the pore remains unknown and specific inhibitors of its opening are lacking, the mitochondrial permeability transition pore remains a target for alleviation of reperfusion injury. Nevertheless, taking conditions such as ageing, sex, comorbidities and co\u2010medication into account may be of paramount importance during the design of pre\u2010clinical and clinical studies testing mitoprotective drugs.<\/jats:p>","DOI":"10.1111\/jcmm.14953","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T11:20:20Z","timestamp":1579692020000},"page":"2717-2729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST\u2010segment elevation myocardial infarction"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-8962","authenticated-orcid":false,"given":"Hans Erik","family":"B\u00f8tker","sequence":"first","affiliation":[{"name":"Department of Cardiology Aarhus University Hospital Aarhus N Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector Alejandro","family":"Cabrera\u2010Fuentes","sequence":"additional","affiliation":[{"name":"SingHealth Duke\u2010NUS Cardiovascular Sciences Academic Clinical Programme and Cardiovascular and Metabolic Disorders Program Duke\u2010National University of Singapore Medical School Singapore Singapore"},{"name":"National Heart Research Institute Singapore National Heart Centre Singapore Singapore"},{"name":"Institute of Biochemistry Medical School Justus\u2010Liebig University Giessen Germany"},{"name":"Tecnologico de Monterrey Centro de Biotecnologia\u2010FEMSA Monterrey Mexico"},{"name":"Institute of Fundamental Medicine and Biology Kazan (Volga Region) Federal University Kazan Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Ruiz\u2010Meana","sequence":"additional","affiliation":[{"name":"Vall d'Hebron Institut de Recerca University Hospital Vall d'Hebron\u2010Universitat Aut\u00f2noma Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red\u2010CV CIBER\u2010CV Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Heusch","sequence":"additional","affiliation":[{"name":"Institute for Pathophysiology West German Heart and Vascular Center University of Essen. 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