Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial

Salahaddin Ubaid; Thomas J Ford; Colin Berry; Heather M Murray; Benjamin Wrigley; Nazish Khan; Mark R Thomas; Angel L Armesilla; Jon N Townend; Saib S Khogali; Shahzad Munir; Joe Martins; Sandeep S Hothi; Elisa J McAlindon; James M Cotton

doi:10.1055/s-0039-1688789

Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial

Salahaddin Ubaid, Thomas J Ford, Colin Berry, Heather M Murray, Benjamin Wrigley, Nazish Khan, Mark R Thomas, Angel L Armesilla, Jon N Townend, Saib S Khogali, Shahzad Munir, Joe Martins, Sandeep S Hothi, Elisa J McAlindon, James M Cotton

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

BACKGROUND: Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery.

OBJECTIVES: This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI).

MATERIALS AND METHODS: In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341).

RESULTS: P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups.

CONCLUSION: Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.

Original language	English
Pages (from-to)	1171-1181
Number of pages	11
Journal	Thrombosis and Haemostasis
Volume	119
Issue number	7
DOIs	https://doi.org/10.1055/s-0039-1688789
Publication status	Published - Jul 2019

Bibliographical note

Georg Thieme Verlag KG Stuttgart · New York.

Keywords

Adenosine Monophosphate/analogs & derivatives
Aged
Blood Platelets/drug effects
Blood Vessels/drug effects
Cells, Cultured
Female
Humans
Male
Microcirculation/drug effects
Middle Aged
Myocardial Infarction/drug therapy
Myocardium/metabolism
Percutaneous Coronary Intervention
Platelet Activation
Platelet Function Tests
Receptors, Purinergic P2Y12/metabolism
Regional Blood Flow/drug effects
Ticagrelor/therapeutic use

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Ubaid, S., Ford, T. J., Berry, C., Murray, H. M., Wrigley, B., Khan, N., Thomas, M. R., Armesilla, A. L., Townend, J. N., Khogali, S. S., Munir, S., Martins, J., Hothi, S. S., McAlindon, E. J., & Cotton, J. M. (2019). Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial. Thrombosis and Haemostasis, 119(7), 1171-1181. https://doi.org/10.1055/s-0039-1688789

@article{566aa2c4178346878939bb8c1b8bb24f,

title = "Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial",

abstract = "BACKGROUND: Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery.OBJECTIVES: This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI).MATERIALS AND METHODS: In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341).RESULTS: P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups.CONCLUSION: Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.",

keywords = "Adenosine Monophosphate/analogs & derivatives, Aged, Blood Platelets/drug effects, Blood Vessels/drug effects, Cells, Cultured, Female, Humans, Male, Microcirculation/drug effects, Middle Aged, Myocardial Infarction/drug therapy, Myocardium/metabolism, Percutaneous Coronary Intervention, Platelet Activation, Platelet Function Tests, Receptors, Purinergic P2Y12/metabolism, Regional Blood Flow/drug effects, Ticagrelor/therapeutic use",

author = "Salahaddin Ubaid and Ford, {Thomas J} and Colin Berry and Murray, {Heather M} and Benjamin Wrigley and Nazish Khan and Thomas, {Mark R} and Armesilla, {Angel L} and Townend, {Jon N} and Khogali, {Saib S} and Shahzad Munir and Joe Martins and Hothi, {Sandeep S} and McAlindon, {Elisa J} and Cotton, {James M}",

note = "Georg Thieme Verlag KG Stuttgart · New York.",

year = "2019",

month = jul,

doi = "10.1055/s-0039-1688789",

language = "English",

volume = "119",

pages = "1171--1181",

journal = "Thrombosis and Haemostasis",

issn = "0340-6245",

publisher = "Schattauer",

number = "7",

}

Ubaid, S, Ford, TJ, Berry, C, Murray, HM, Wrigley, B, Khan, N, Thomas, MR, Armesilla, AL, Townend, JN, Khogali, SS, Munir, S, Martins, J, Hothi, SS, McAlindon, EJ & Cotton, JM 2019, 'Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial', Thrombosis and Haemostasis, vol. 119, no. 7, pp. 1171-1181. https://doi.org/10.1055/s-0039-1688789

Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial. / Ubaid, Salahaddin; Ford, Thomas J; Berry, Colin et al.
In: Thrombosis and Haemostasis, Vol. 119, No. 7, 07.2019, p. 1171-1181.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention

T2 - Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial

AU - Ubaid, Salahaddin

AU - Ford, Thomas J

AU - Berry, Colin

AU - Murray, Heather M

AU - Wrigley, Benjamin

AU - Khan, Nazish

AU - Thomas, Mark R

AU - Armesilla, Angel L

AU - Townend, Jon N

AU - Khogali, Saib S

AU - Munir, Shahzad

AU - Martins, Joe

AU - Hothi, Sandeep S

AU - McAlindon, Elisa J

AU - Cotton, James M

N1 - Georg Thieme Verlag KG Stuttgart · New York.

PY - 2019/7

Y1 - 2019/7

N2 - BACKGROUND: Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery.OBJECTIVES: This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI).MATERIALS AND METHODS: In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341).RESULTS: P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups.CONCLUSION: Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.

AB - BACKGROUND: Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery.OBJECTIVES: This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI).MATERIALS AND METHODS: In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341).RESULTS: P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups.CONCLUSION: Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.

KW - Adenosine Monophosphate/analogs & derivatives

KW - Aged

KW - Blood Platelets/drug effects

KW - Blood Vessels/drug effects

KW - Cells, Cultured

KW - Female

KW - Humans

KW - Male

KW - Microcirculation/drug effects

KW - Middle Aged

KW - Myocardial Infarction/drug therapy

KW - Myocardium/metabolism

KW - Percutaneous Coronary Intervention

KW - Platelet Activation

KW - Platelet Function Tests

KW - Receptors, Purinergic P2Y12/metabolism

KW - Regional Blood Flow/drug effects

KW - Ticagrelor/therapeutic use

U2 - 10.1055/s-0039-1688789

DO - 10.1055/s-0039-1688789

M3 - Article

C2 - 31129911

SN - 0340-6245

VL - 119

SP - 1171

EP - 1181

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

IS - 7

ER -