• Noel M Caplice, Mary C DeVoe, Janet Choi, Darren Dahly, Theodore Murphy, Ernest Spitzer, Robert Van Geuns, Michael M Maher, David Tuite, David M Kerins, Mohammed T Ali, Imtiaz Kalyar, Eoin F Fahy, Wisam Khider, Peter Kelly, Peter P Kearney, Ronan J Curtin, Conor O'Shea, Carl J Vaughan, Joseph A Eustace, and Eugene P McFadden.
• Department of Cardiology, Cork University Hospital, Wilton Rd, Cork, Ireland; Centre for Research in Vascular Biology, University College Cork, Cork, Ireland. Electronic address: n.caplice@ucc.ie.
• Am. Heart J. 2018 Jun 1; 200: 110-117.

BackgroundResidual and significant postinfarction 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 remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients.MethodsUsing a double-blind, placebo-controlled, multidose 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), 1.5 ng IGF1 (n = 16), or 15 ng IGF1 (n = 16). All received optimal medical therapy. Safety end points were freedom from hypoglycemia, hypotension, or significant arrhythmias within 1 hour of therapy. The primary efficacy end point was LVEF, and secondary end points were LV volumes, mass, stroke volume, and infarct size at 2-month follow-up, all assessed by magnetic resonance imaging. Treatment effects were estimated by analysis of covariance adjusted for baseline (24 hours) outcome.ResultsNo significant differences in safety end points occurred between treatment groups out to 30 days (χ2 test, P value = .77). There were no statistically significant differences in baseline (24 hours 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 1.5 ng IGF1, treatment with 15 ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (P = .018), LV mass (P = .004), and stroke volume (P = .016). Late gadolinium enhancement (±SD) at 2 months was lower in 15 ng IGF1 (34.5 ± 29.6 g) compared to placebo (49.1 ± 19.3 g) or 1.5 ng IGF1 (47.4 ± 22.4 g) treated patients, although the result was not statistically significant (P = .095).ConclusionsIn 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.Copyright © 2018. Published by Elsevier Inc.

38 keywords...

hide…