caa a22 4500 606158707 CHVBK 20210128100621.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s10557-015-6615-4 doi (NATIONALLICENCE)springer-10.1007/s10557-015-6615-4 Statin-Induced Cardioprotection Against Ischemia-Reperfusion Injury: Potential Drug-Drug Interactions. Lesson to be Learnt by Translating Results from Animal Models to the Clinical Settings [Elektronische Daten] [Gilad Birnbaum, Itamar Birnbaum, Yumei Ye, Yochai Birnbaum] Numerous interventions have been shown to limit myocardial infarct size in animal models; however, most of these interventions have failed to have a significant effect in clinical trials. One potential explanation for the lack of efficacy in the clinical setting is that in bench models, a single intervention is studied without the background of other interventions or modalities. This is in contrast to the clinical setting in which new medications are added to the "standard of care” treatment that by now includes a growing number of medications. Drug-drug interaction may lead to alteration, dampening, augmenting or masking the effects of the intended intervention. We use the well described model of statin-induced myocardial protection to demonstrate potential interactions with agents which are commonly concomitantly used in patients with stable coronary artery disease and/or acute coronary syndromes. These interactions could potentially explain the reduced efficacy of statins in the clinical trials compared to the animal models. In particular, caffeine and aspirin could attenuate the infarct size limiting effects of statins; morphine could delay the onset of protection or mask the protective effect in patients with ST elevation myocardial infarction, whereas other anti-platelet agents (dipyridamole, cilostazol and ticagrelor) may augment (or mask) the effect due to their favorable effects on adenosine cell reuptake and intracellular cAMP levels. We recommend that after characterizing the effects of new modalities in single intervention bench research, studies should be repeated in the background of standard-of-care medications to assure that the magnitude of the effect is not altered before proceeding with clinical trials. Springer Science+Business Media New York, 2015 Statins nationallicence Adenosine nationallicence Cyclooxygenase-2 nationallicence Infarct size nationallicence Drug interaction nationallicence Animal models nationallicence Clinical trials nationallicence Morphine nationallicence Diabetic drugs nationallicence Birnbaum Gilad The Department of Medicine, Baylor College of Medicine, Houston, TX, USA aut Birnbaum Itamar The Section of Cardiology, Baylor College of Medicine, MS: BCM620, One Baylor Plaza, 77030, Houston, TX, USA aut Ye Yumei The Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA aut Birnbaum Yochai The Section of Cardiology, Baylor College of Medicine, MS: BCM620, One Baylor Plaza, 77030, Houston, TX, USA aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/5(2015-10-01), 461-467 0920-3206 29:5<461 2015 29 10557 https://doi.org/10.1007/s10557-015-6615-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-015-6615-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Birnbaum Gilad The Department of Medicine, Baylor College of Medicine, Houston, TX, USA aut NATIONALLICENCE 700 1- Birnbaum Itamar The Section of Cardiology, Baylor College of Medicine, MS: BCM620, One Baylor Plaza, 77030, Houston, TX, USA aut NATIONALLICENCE 700 1- Ye Yumei The Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA aut NATIONALLICENCE 700 1- Birnbaum Yochai The Section of Cardiology, Baylor College of Medicine, MS: BCM620, One Baylor Plaza, 77030, Houston, TX, USA aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/5(2015-10-01), 461-467 0920-3206 29:5<461 2015 29 10557