Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel

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

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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
Number of pages11
JournalCirculation
Volume139
Issue number5
DOIs
Publication statusPublished - 29 Jan 2019
Externally publishedYes

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Wounds and Injuries
Percutaneous Coronary Intervention
Ticagrelor
ST Elevation Myocardial Infarction
Prasugrel Hydrochloride
Adenosine
Therapeutics
Microcirculation
Arteries
Magnetic Resonance Imaging
Clinical Trials
Hemorrhage

Keywords

  • microvessels
  • prasugrel hydrochloride
  • ST elevation myocardial infarction
  • ticagrelor

Cite this

van Leeuwen, M. A. H., van der Hoeven, N. W., Janssens, G. N., Everaars, H., Nap, A., Lemkes, J. S., ... van Royen, N. (2019). Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel. Circulation, 139(5), 636-646. https://doi.org/10.1161/CIRCULATIONAHA.118.035931
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. / Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel. In: Circulation. 2019 ; Vol. 139, No. 5. pp. 636-646.
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title = "Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel",
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.",
keywords = "microvessels, prasugrel hydrochloride, ST elevation myocardial infarction, ticagrelor",
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",
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van Leeuwen, MAH, van der Hoeven, NW, Janssens, GN, Everaars, H, Nap, A, Lemkes, JS, de Waard, GA, van de Ven, PM, van Rossum, AC, Ten Cate, TJF, Piek, JJ, von Birgelen, C, Escaned, J, Valgimigli, M, Diletti, R, Riksen, NP, van Mieghem, NM, Nijveldt, R & van Royen, N 2019, 'Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel' Circulation, vol. 139, no. 5, pp. 636-646. https://doi.org/10.1161/CIRCULATIONAHA.118.035931

Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel. / 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, 29.01.2019, p. 636-646.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel

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 - 2019/1/29

Y1 - 2019/1/29

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.

KW - microvessels

KW - prasugrel hydrochloride

KW - ST elevation myocardial infarction

KW - ticagrelor

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U2 - 10.1161/CIRCULATIONAHA.118.035931

DO - 10.1161/CIRCULATIONAHA.118.035931

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VL - 139

SP - 636

EP - 646

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 5

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