Evaluation of Microvascular Injury in Revascularized Patients with ST Elevation Myocardial Infarction Treated with Ticagrelor versus Prasugrel: The REDUCE-MVI Trial

Maarten A. H. van Leeuwen, Nina W. van der Hoeven, Gladys N. Janssens, Henk Everaars, Alexander Nap, Jorrit S. Lemkes, Guus A. de Waard, Peter M. van de Ven, Albert C. van Rossum, Tim J. F. ten Cate, Jan J. Piek, Clemens von Birgelen, Javier Escaned, Marco Valgimigli, Roberto Diletti, Niels P. Riksen, Nicolas M. van Mieghem, Robin Nijveldt, Niels van Royen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy. METHODS: A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month. RESULTS: The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23% versus 43%; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.
Original languageEnglish
Pages (from-to)636-646
JournalCirculation
Volume139
Issue number5
Early online date30 Oct 2018
DOIs
Publication statusPublished - 2019

Cite this

@article{811dc96a74ca419987a9e48193c5cee3,
title = "Evaluation of Microvascular Injury in Revascularized Patients with ST Elevation Myocardial Infarction Treated with Ticagrelor versus Prasugrel: The REDUCE-MVI Trial",
abstract = "BACKGROUND: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy. METHODS: A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month. RESULTS: The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23{\%} versus 43{\%}; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28{\%}) or prasugrel (41{\%}; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.",
author = "{van Leeuwen}, {Maarten A. H.} and {van der Hoeven}, {Nina W.} and Janssens, {Gladys N.} and Henk Everaars and Alexander Nap and Lemkes, {Jorrit S.} and {de Waard}, {Guus A.} and {van de Ven}, {Peter M.} and {van Rossum}, {Albert C.} and {ten Cate}, {Tim J. F.} and Piek, {Jan J.} and {von Birgelen}, Clemens and Javier Escaned and Marco Valgimigli and Roberto Diletti and Riksen, {Niels P.} and {van Mieghem}, {Nicolas M.} and Robin Nijveldt and {van Royen}, Niels",
year = "2019",
doi = "10.1161/CIRCULATIONAHA.118.035931",
language = "English",
volume = "139",
pages = "636--646",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

Evaluation of Microvascular Injury in Revascularized Patients with ST Elevation Myocardial Infarction Treated with Ticagrelor versus Prasugrel : The REDUCE-MVI Trial. / van Leeuwen, Maarten A. H.; van der Hoeven, Nina W.; Janssens, Gladys N.; Everaars, Henk; Nap, Alexander; Lemkes, Jorrit S.; de Waard, Guus A.; van de Ven, Peter M.; van Rossum, Albert C.; ten Cate, Tim J. F.; Piek, Jan J.; von Birgelen, Clemens; Escaned, Javier; Valgimigli, Marco; Diletti, Roberto; Riksen, Niels P.; van Mieghem, Nicolas M.; Nijveldt, Robin; van Royen, Niels.

In: Circulation, Vol. 139, No. 5, 2019, p. 636-646.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Evaluation of Microvascular Injury in Revascularized Patients with ST Elevation Myocardial Infarction Treated with Ticagrelor versus Prasugrel

T2 - The REDUCE-MVI Trial

AU - van Leeuwen, Maarten A. H.

AU - van der Hoeven, Nina W.

AU - Janssens, Gladys N.

AU - Everaars, Henk

AU - Nap, Alexander

AU - Lemkes, Jorrit S.

AU - de Waard, Guus A.

AU - van de Ven, Peter M.

AU - van Rossum, Albert C.

AU - ten Cate, Tim J. F.

AU - Piek, Jan J.

AU - von Birgelen, Clemens

AU - Escaned, Javier

AU - Valgimigli, Marco

AU - Diletti, Roberto

AU - Riksen, Niels P.

AU - van Mieghem, Nicolas M.

AU - Nijveldt, Robin

AU - van Royen, Niels

PY - 2019

Y1 - 2019

N2 - BACKGROUND: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy. METHODS: A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month. RESULTS: The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23% versus 43%; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.

AB - BACKGROUND: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy. METHODS: A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month. RESULTS: The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23% versus 43%; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30586720

U2 - 10.1161/CIRCULATIONAHA.118.035931

DO - 10.1161/CIRCULATIONAHA.118.035931

M3 - Article

VL - 139

SP - 636

EP - 646

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 5

ER -