Randomized placebo controlled trial evaluating the safety and efficacy of single low dose intracoronary insulin like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI)

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dc.contributor.author Caplice, Noel M.
dc.contributor.author DeVoe, Mary C.
dc.contributor.author Choi, Janet
dc.contributor.author Dahly, Darren L.
dc.contributor.author Murphy, Theodore
dc.contributor.author Spitzer, Ernest
dc.contributor.author Van Geuns, Robert
dc.contributor.author Maher, Michael M.
dc.contributor.author Tuite, David
dc.contributor.author Kerins, David M.
dc.contributor.author Ali, Mohammed T.
dc.contributor.author Kalyar, Imtiaz
dc.contributor.author Fahy, Eoin F.
dc.contributor.author Khider, Wisam
dc.contributor.author Kelly, Peter
dc.contributor.author Kearney, Peter P.
dc.contributor.author Curtin, Ronan J.
dc.contributor.author O'Shea, Conor
dc.contributor.author Vaughan, Carl J.
dc.contributor.author Eustace, Joseph A.
dc.contributor.author McFadden, Eugene P.
dc.date.accessioned 2018-04-16T11:13:06Z
dc.date.available 2018-04-16T11:13:06Z
dc.date.issued 2018-04-03
dc.identifier.citation Caplice, N. M., DeVoe, M. C., Choi, J., Dahly, D., Murphy, T., Spitzer, E., Van Geuns, R., Maher, M. M., Tuite, D., Kerins, D. M., T.Ali, M., Kalyar, I., Fahy, E. F., Khider, W., Kelly, P., Kearney, P. P., Curtin, R. J., O’Shea, C., Vaughan, C. J., Eustace, J. A. and McFadden, E. P. 'Randomized placebo controlled trial evaluating the safety and efficacy of single low dose intracoronary insulin like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI)', American Heart Journal, In Press. doi: 10.1016/j.ahj.2018.03.018 en
dc.identifier.startpage 1 en
dc.identifier.endpage 24 en
dc.identifier.issn 0002-8703
dc.identifier.uri http://hdl.handle.net/10468/5770
dc.identifier.doi 10.1016/j.ahj.2018.03.018
dc.description.abstract Background: Residual and significant post-infarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models low dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodelling effects. We studied the safety and efficacy of immediate post PCI low dose intracoronary IGF1 infusion in STEMI patients. Methods: Using a double-blind, placebo controlled, multi-dose study design, we randomized 47 STEMI patients with significantly reduced (≤ 40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n=15), 1.5ng IGF1 (n=16) or 15ng IGF1 (n=16). All received optimal medical therapy. Safety endpoints were freedom from hypoglycaemia, hypotension or significant arrhythmias within 1 hour of therapy. The primary efficacy endpoint was LVEF and secondary endpoints were LV volumes, mass, stroke volume, and infarct size at 2 months follow up, all assessed by MRI. Treatment effects were estimated by analysis of covariance adjusted for baseline (24hrs) outcome. Results: No significant differences in safety endpoints occurred between treatment groups out to 30 days (chi squared test, p-value = 0.77).There were no statistically significant differences in baseline (24 hrs post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5ng IGF1, treatment with 15ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (p=0.018), LV mass (p=0.004) and stroke volume (p=0.016). Late gadolinium enhancement (±SD) at 2 months was lower in 15ng IGF1 (34.5±29.6g) compared to placebo (49.1±19.3g) or 1.5ng IGF1 (47.4±22.4g) treated patients, though the result was not statistically significant (p = 0.095). Conclusion: In this pilot trial, low dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose dependent benefit on post MI remodeling that may warrant further study. Despite timely reperfusion by primary PCI (PPCI) a significant cohort of patients develop adverse left ventricular remodelling with clinical sequelae such as arrhythmia and heart failure[1].Therapeutic approaches to avert such remodeling, including a variety of cell therapy and ischemia- reperfusion-injury mitigation trials have achieved modest success 2.;3. Thus, there remains a significant opportunity for novel therapies in this field. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.uri https://www.sciencedirect.com/science/article/pii/S0002870318301029
dc.rights © 2018 Published by Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Acute myocardial infarction en
dc.subject Post-infarction left ventricular (LV) dysfunction en
dc.subject STEMI en
dc.subject Clinical trial en
dc.title Randomized placebo controlled trial evaluating the safety and efficacy of single low dose intracoronary insulin like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI) en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Noel Caplice, Medicine Department, University College Cork, Cork, Ireland. +353-21-490-3000 Email: n.caplice@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2019-04-03
dc.date.updated 2018-04-16T10:59:27Z
dc.description.version Accepted Version en
dc.internal.rssid 434076154
dc.contributor.funder Health Research Board en
dc.description.status Peer reviewed en
dc.identifier.journaltitle American Heart Journal en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress n.caplice@ucc.ie en
dc.internal.bibliocheck In Press April 2018. Update citation details, page numbers, add vol, issue en
dc.relation.project info:eu-repo/grantAgreement/SFI/HRB-SFI Translational Research Awards/TRA/2010/20/IE/Mechanism of benefit and clinical efficacy of low insulin-like growth factor 1 in acute myocardial infarct repair/ en


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© 2018 Published by Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. Except where otherwise noted, this item's license is described as © 2018 Published by Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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