Stroke outcomes with vorapaxar versus placebo in patients with acute coronary syndromes: Insights from the TRACER trial

Leo Ungar; Robert M. Clare; Fatima Rodriguez; Bradley J. Kolls; Paul W. Armstrong; Philip Aylward; Claes Held; David J. Moliterno; John Strony; Frans Van de Werf; Lars Wallentin; Harvey D. White; Pierluigi Tricoci; Robert A. Harrington; Kenneth W. Mahaffey; Chiara Melloni

doi:10.1161/JAHA.118.009609

Stroke outcomes with vorapaxar versus placebo in patients with acute coronary syndromes: Insights from the TRACER trial

Leo Ungar, Robert M. Clare, Fatima Rodriguez, Bradley J. Kolls, Paul W. Armstrong, Philip Aylward, Claes Held, David J. Moliterno, John Strony, Frans Van de Werf, Lars Wallentin, Harvey D. White, Pierluigi Tricoci, Robert A. Harrington, Kenneth W. Mahaffey, Chiara Melloni

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Abstract

Background-Vorapaxar, a protease-activated receptor-1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage. Methods and Results-TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow-up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan-Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22-6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58-1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71-1.24]). Conclusions-Stroke occurred in <2% of patients. Vorapaxar-assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.

Original language	English
Article number	e009609
Number of pages	13
Journal	Journal of the American Heart Association
Volume	7
Issue number	24
DOIs	https://doi.org/10.1161/JAHA.118.009609
Publication status	Published - 18 Dec 2018
Externally published	Yes

Bibliographical note

Copyright © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Keywords

Acute coronary syndrome
Stroke
Vorapaxar

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10.1161/JAHA.118.009609Licence: CC BY

Ungar_Stroke_P2018Final published version, 721 KBLicence: CC BY

Cite this

Ungar, L., Clare, R. M., Rodriguez, F., Kolls, B. J., Armstrong, P. W., Aylward, P., Held, C., Moliterno, D. J., Strony, J., Van de Werf, F., Wallentin, L., White, H. D., Tricoci, P., Harrington, R. A., Mahaffey, K. W., & Melloni, C. (2018). Stroke outcomes with vorapaxar versus placebo in patients with acute coronary syndromes: Insights from the TRACER trial. Journal of the American Heart Association, 7(24), Article e009609. https://doi.org/10.1161/JAHA.118.009609

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title = "Stroke outcomes with vorapaxar versus placebo in patients with acute coronary syndromes: Insights from the TRACER trial",

abstract = "Background-Vorapaxar, a protease-activated receptor-1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage. Methods and Results-TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow-up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan-Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22-6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58-1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71-1.24]). Conclusions-Stroke occurred in <2% of patients. Vorapaxar-assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.",

keywords = "Acute coronary syndrome, Stroke, Vorapaxar",

author = "Leo Ungar and Clare, {Robert M.} and Fatima Rodriguez and Kolls, {Bradley J.} and Armstrong, {Paul W.} and Philip Aylward and Claes Held and Moliterno, {David J.} and John Strony and {Van de Werf}, Frans and Lars Wallentin and White, {Harvey D.} and Pierluigi Tricoci and Harrington, {Robert A.} and Mahaffey, {Kenneth W.} and Chiara Melloni",

note = "Copyright {\textcopyright} 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.",

year = "2018",

month = dec,

day = "18",

doi = "10.1161/JAHA.118.009609",

language = "English",

volume = "7",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "AHA Journals",

number = "24",

}

Ungar, L, Clare, RM, Rodriguez, F, Kolls, BJ, Armstrong, PW, Aylward, P, Held, C, Moliterno, DJ, Strony, J, Van de Werf, F, Wallentin, L, White, HD, Tricoci, P, Harrington, RA, Mahaffey, KW & Melloni, C 2018, 'Stroke outcomes with vorapaxar versus placebo in patients with acute coronary syndromes: Insights from the TRACER trial', Journal of the American Heart Association, vol. 7, no. 24, e009609. https://doi.org/10.1161/JAHA.118.009609

TY - JOUR

T1 - Stroke outcomes with vorapaxar versus placebo in patients with acute coronary syndromes

T2 - Insights from the TRACER trial

AU - Ungar, Leo

AU - Clare, Robert M.

AU - Rodriguez, Fatima

AU - Kolls, Bradley J.

AU - Armstrong, Paul W.

AU - Aylward, Philip

AU - Held, Claes

AU - Moliterno, David J.

AU - Strony, John

AU - Van de Werf, Frans

AU - Wallentin, Lars

AU - White, Harvey D.

AU - Tricoci, Pierluigi

AU - Harrington, Robert A.

AU - Mahaffey, Kenneth W.

AU - Melloni, Chiara

N1 - Copyright © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

PY - 2018/12/18

Y1 - 2018/12/18

N2 - Background-Vorapaxar, a protease-activated receptor-1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage. Methods and Results-TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow-up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan-Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22-6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58-1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71-1.24]). Conclusions-Stroke occurred in <2% of patients. Vorapaxar-assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.

AB - Background-Vorapaxar, a protease-activated receptor-1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage. Methods and Results-TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow-up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan-Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22-6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58-1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71-1.24]). Conclusions-Stroke occurred in <2% of patients. Vorapaxar-assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.

KW - Acute coronary syndrome

KW - Stroke

KW - Vorapaxar

UR - http://www.scopus.com/inward/record.url?scp=85058590086&partnerID=8YFLogxK

U2 - 10.1161/JAHA.118.009609

DO - 10.1161/JAHA.118.009609

M3 - Article

C2 - 30526198

AN - SCOPUS:85058590086

SN - 2047-9980

VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 24

M1 - e009609

ER -

Stroke outcomes with vorapaxar versus placebo in patients with acute coronary syndromes: Insights from the TRACER trial

Abstract

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