Type

Journal Article

Authors

Eugene P. McFadden
Joseph A Eustace
Carl J. Vaughan
Conor O'Shea
Ronan J Curtin
Peter P. Kearney
Peter Kelly
Wisam Khider
Eoin F. Fahy
Imtiaz Kalyar
and 11 others

Subjects

Medicine & Nursing

Topics
acute myocardial infarction stemi clinical trial reperfusion injury controlled growth post infarction left ventricular lv dysfunction stroke volume low dose

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) (2018)

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.
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Full list of authors on original publication

Eugene P. McFadden, Joseph A Eustace, Carl J. Vaughan, Conor O'Shea, Ronan J Curtin, Peter P. Kearney, Peter Kelly, Wisam Khider, Eoin F. Fahy, Imtiaz Kalyar and 11 others

Experts in our system

1
Joseph A Eustace
University College Cork
Total Publications: 36
 
2
Conor O'Shea
University College Cork
Total Publications: 4
 
3
Ronan J Curtin
University College Cork
Total Publications: 6
 
4
Peter J Kelly
University College Dublin
Total Publications: 48
 
5
Wisam Khider
University College Cork
Total Publications: 4