Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: A phase 2 randomised clinical trial

Thomas Engstrøm; Lars Nepper-Christensen; Steffen Helqvist; Lene Kløvgaard; Lene Holmvang; Erik Jørgensen; Frants Pedersen; Kari Saunamaki; Hans Henrik Tilsted; Adam Steensberg; Søren Fabricius; Ulrik Mouritzen; Niels Vejlstrup; Kiril A. Ahtarovski; Christoffer Göransson; Litten Bertelsen; Kasper Kyhl; Göran Olivecrona; Henning Kelbæk; Jens Flensted Lassen; Lars Køber; Jacob Lønborg

doi:10.1136/heartjnl-2017-312774

Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: A phase 2 randomised clinical trial

Thomas Engstrøm^*, Lars Nepper-Christensen, Steffen Helqvist, Lene Kløvgaard, Lene Holmvang, Erik Jørgensen, Frants Pedersen, Kari Saunamaki, Hans Henrik Tilsted, Adam Steensberg, Søren Fabricius, Ulrik Mouritzen, Niels Vejlstrup, Kiril A. Ahtarovski, Christoffer Göransson, Litten Bertelsen, Kasper Kyhl, Göran Olivecrona, Henning Kelbæk, Jens Flensted LassenLars Køber, Jacob Lønborg

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

11 Citationer (Scopus)

Abstract

Objectives Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions Administration of danegaptide to patients with STEMI did not improve myocardial salvage.

Originalsprog	Engelsk
Tidsskrift	Heart
Vol/bind	104
Udgave nummer	19
Sider (fra-til)	1593-1599
Antal sider	7
ISSN	1355-6037
DOI	https://doi.org/10.1136/heartjnl-2017-312774
Status	Udgivet - 2018

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10.1136/heartjnl-2017-312774

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Citationsformater

Engstrøm, T., Nepper-Christensen, L., Helqvist, S., Kløvgaard, L., Holmvang, L., Jørgensen, E., Pedersen, F., Saunamaki, K., Tilsted, H. H., Steensberg, A., Fabricius, S., Mouritzen, U., Vejlstrup, N., Ahtarovski, K. A., Göransson, C., Bertelsen, L., Kyhl, K., Olivecrona, G., Kelbæk, H., ... Lønborg, J. (2018). Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: A phase 2 randomised clinical trial. Heart, 104(19), 1593-1599. https://doi.org/10.1136/heartjnl-2017-312774

Engstrøm, T, Nepper-Christensen, L, Helqvist, S, Kløvgaard, L, Holmvang, L, Jørgensen, E, Pedersen, F, Saunamaki, K, Tilsted, HH, Steensberg, A, Fabricius, S, Mouritzen, U, Vejlstrup, N, Ahtarovski, KA, Göransson, C, Bertelsen, L, Kyhl, K, Olivecrona, G, Kelbæk, H, Lassen, JF, Køber, L & Lønborg, J 2018, 'Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: A phase 2 randomised clinical trial', Heart, bind 104, nr. 19, s. 1593-1599. https://doi.org/10.1136/heartjnl-2017-312774

@article{3bf4ea3b110f40b6a3286763fa7e3659,

title = "Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: A phase 2 randomised clinical trial",

abstract = "Objectives Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions Administration of danegaptide to patients with STEMI did not improve myocardial salvage.",

keywords = "acute myocardial infarction, cardiac magnetic resonance (cmr) imaging, percutaneous coronary intervention",

author = "Thomas Engstr{\o}m and Lars Nepper-Christensen and Steffen Helqvist and Lene Kl{\o}vgaard and Lene Holmvang and Erik J{\o}rgensen and Frants Pedersen and Kari Saunamaki and Tilsted, {Hans Henrik} and Adam Steensberg and S{\o}ren Fabricius and Ulrik Mouritzen and Niels Vejlstrup and Ahtarovski, {Kiril A.} and Christoffer G{\"o}ransson and Litten Bertelsen and Kasper Kyhl and G{\"o}ran Olivecrona and Henning Kelb{\ae}k and Lassen, {Jens Flensted} and Lars K{\o}ber and Jacob L{\o}nborg",

year = "2018",

doi = "10.1136/heartjnl-2017-312774",

language = "English",

volume = "104",

pages = "1593--1599",

journal = "Heart",

issn = "1355-6037",

publisher = "B M J Group",

number = "19",

}

TY - JOUR

T1 - Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients

T2 - A phase 2 randomised clinical trial

AU - Engstrøm, Thomas

AU - Nepper-Christensen, Lars

AU - Helqvist, Steffen

AU - Kløvgaard, Lene

AU - Holmvang, Lene

AU - Jørgensen, Erik

AU - Pedersen, Frants

AU - Saunamaki, Kari

AU - Tilsted, Hans Henrik

AU - Steensberg, Adam

AU - Fabricius, Søren

AU - Mouritzen, Ulrik

AU - Vejlstrup, Niels

AU - Ahtarovski, Kiril A.

AU - Göransson, Christoffer

AU - Bertelsen, Litten

AU - Kyhl, Kasper

AU - Olivecrona, Göran

AU - Kelbæk, Henning

AU - Lassen, Jens Flensted

AU - Køber, Lars

AU - Lønborg, Jacob

PY - 2018

Y1 - 2018

N2 - Objectives Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions Administration of danegaptide to patients with STEMI did not improve myocardial salvage.

AB - Objectives Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions Administration of danegaptide to patients with STEMI did not improve myocardial salvage.

KW - acute myocardial infarction

KW - cardiac magnetic resonance (cmr) imaging

KW - percutaneous coronary intervention

U2 - 10.1136/heartjnl-2017-312774

DO - 10.1136/heartjnl-2017-312774

M3 - Journal article

C2 - 29602883

AN - SCOPUS:85049134939

SN - 1355-6037

VL - 104

SP - 1593

EP - 1599

JO - Heart

JF - Heart

IS - 19

ER -

Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: A phase 2 randomised clinical trial

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