Reperfusion after Fibrinolytic Therapy (RAFT): An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention

Amir Faour; Nicholas Collins; Trent Williams; Arshad Khan; Craig P. Juergens; Sidney Lo; Darren L. Walters; Derek P. Chew; John K. French

doi:10.1371/journal.pone.0259148

Reperfusion after Fibrinolytic Therapy (RAFT): An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention

Amir Faour, Nicholas Collins, Trent Williams, Arshad Khan, Craig P. Juergens, Sidney Lo, Darren L. Walters, Derek P. Chew, John K. French

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Abstract

Background The safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI. Objectives We conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI. Methods Between 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score. Results The trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin. Conclusions Whether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022).

Original language	English
Article number	e0259148
Number of pages	18
Journal	PLoS One
Volume	16
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0259148
Publication status	Published - Oct 2021
Externally published	Yes

Bibliographical note

Funding Information:
JKF received an unrestricted educational research grant from The Medicines Company (New Jersey, USA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Medicines Company provided support in the form of salary for author DC almost a decade predating this study (2001-2002 [12-months]), with no ongoing direct funding support since. The specific roles of these authors are articulated in the ?author contributions? section. The authors wish to thank the many cardiologists and nursing staff whose help was critical to recruiting patients for this trial.

Publisher Copyright:
Copyright: © 2021 Faour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

Reperfusion After Fibrinolytic Therapy
bivalirudin
heparin
coronary intervention

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Faour, A., Collins, N., Williams, T., Khan, A., Juergens, C. P., Lo, S., Walters, D. L., Chew, D. P., & French, J. K. (2021). Reperfusion after Fibrinolytic Therapy (RAFT): An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention. PLoS One, 16(10), Article e0259148. https://doi.org/10.1371/journal.pone.0259148

@article{590a7588bbc54def8704e89b9b3baaaf,

title = "Reperfusion after Fibrinolytic Therapy (RAFT): An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention",

abstract = "Background The safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI. Objectives We conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI. Methods Between 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score. Results The trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin. Conclusions Whether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022).",

keywords = "Reperfusion After Fibrinolytic Therapy, bivalirudin, heparin, coronary intervention",

author = "Amir Faour and Nicholas Collins and Trent Williams and Arshad Khan and Juergens, {Craig P.} and Sidney Lo and Walters, {Darren L.} and Chew, {Derek P.} and French, {John K.}",

note = "Funding Information: JKF received an unrestricted educational research grant from The Medicines Company (New Jersey, USA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Medicines Company provided support in the form of salary for author DC almost a decade predating this study (2001-2002 [12-months]), with no ongoing direct funding support since. The specific roles of these authors are articulated in the ?author contributions? section. The authors wish to thank the many cardiologists and nursing staff whose help was critical to recruiting patients for this trial. Publisher Copyright: Copyright: {\textcopyright} 2021 Faour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2021",

month = oct,

doi = "10.1371/journal.pone.0259148",

language = "English",

volume = "16",

journal = "PLoS One",

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publisher = "PlosOne",

number = "10",

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TY - JOUR

T1 - Reperfusion after Fibrinolytic Therapy (RAFT)

T2 - An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention

AU - Faour, Amir

AU - Collins, Nicholas

AU - Williams, Trent

AU - Khan, Arshad

AU - Juergens, Craig P.

AU - Lo, Sidney

AU - Walters, Darren L.

AU - Chew, Derek P.

AU - French, John K.

N1 - Funding Information: JKF received an unrestricted educational research grant from The Medicines Company (New Jersey, USA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Medicines Company provided support in the form of salary for author DC almost a decade predating this study (2001-2002 [12-months]), with no ongoing direct funding support since. The specific roles of these authors are articulated in the ?author contributions? section. The authors wish to thank the many cardiologists and nursing staff whose help was critical to recruiting patients for this trial. Publisher Copyright: Copyright: © 2021 Faour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2021/10

Y1 - 2021/10

N2 - Background The safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI. Objectives We conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI. Methods Between 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score. Results The trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin. Conclusions Whether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022).

AB - Background The safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI. Objectives We conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI. Methods Between 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score. Results The trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin. Conclusions Whether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022).

KW - Reperfusion After Fibrinolytic Therapy

KW - bivalirudin

KW - heparin

KW - coronary intervention

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ER -

Reperfusion after Fibrinolytic Therapy (RAFT): An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention

Abstract

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Keywords

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