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)

Simple item page
dc.contributor.authorCaplice, Noel M.
dc.contributor.authorDeVoe, Mary C.
dc.contributor.authorChoi, Janet
dc.contributor.authorDahly, Darren L.
dc.contributor.authorMurphy, Theodore
dc.contributor.authorSpitzer, Ernest
dc.contributor.authorVan Geuns, Robert
dc.contributor.authorMaher, Michael M.
dc.contributor.authorTuite, David
dc.contributor.authorKerins, David M.
dc.contributor.authorAli, Mohammed T.
dc.contributor.authorKalyar, Imtiaz
dc.contributor.authorFahy, Eoin F.
dc.contributor.authorKhider, Wisam
dc.contributor.authorKelly, Peter
dc.contributor.authorKearney, Peter P.
dc.contributor.authorCurtin, Ronan J.
dc.contributor.authorO'Shea, Conor
dc.contributor.authorVaughan, Carl J.
dc.contributor.authorEustace, Joseph A.
dc.contributor.authorMcFadden, Eugene P.
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2018-04-16T11:13:06Z
dc.date.available2018-04-16T11:13:06Z
dc.date.issued2018-04-03
dc.date.updated2018-04-16T10:59:27Z
dc.description.abstractBackground: 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.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationCaplice, 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.2018.03.018en
dc.identifier.doi10.1016/j.ahj.2018.03.018
dc.identifier.endpage24en
dc.identifier.issn0002-8703
dc.identifier.journaltitleAmerican Heart Journalen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/5770
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo: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
dc.relation.urihttps://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.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectAcute myocardial infarctionen
dc.subjectPost-infarction left ventricular (LV) dysfunctionen
dc.subjectSTEMIen
dc.subjectClinical trialen
dc.titleRandomized 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.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
5233.pdf
Size:
684.19 KB
Format:
Adobe Portable Document Format
Description:
Accepted version
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Medicine - Journal Articles