Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54

Marc P. Bonaca, Deepak L. Bhatt, P. Gabriel Steg, Robert F. Storey, Marc Cohen, Kyungah Im, Ton Oude Ophuis, Andrej Budaj, Shinya Goto, José López-Sendón, Rafael Diaz, Anthony Dalby, Frans Van De Werf, Diego Ardissino, Gilles Montalescot, Philip Aylward, Giulia Magnani, Eva C. Jensen, Peter Held, Eugene Braunwald & 1 others Marc S. Sabatine

Research output: Contribution to journalArticle

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Abstract

Aims Ticagrelor reduced major adverse cardiovascular event (MACE) by 15-16% in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y12 inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of therapy. Methods and results Patients in PEGASUS-TIMI 54 were categorized by time from last P2Y12 inhibitor (days: ≤30, >30-360, >360). The risk of MACE and the efficacy of ticagrelor were compared across categories. In the placebo arm, patients who more recently stopped P2Y12 inhibitor therapy had a greater number of risk factors but still had a higher risk of MACE after multivariable adjustment [≤30 days, hazard ratio (HR)adj 1.47, 95% confidence interval (CI) 1.12-1.93, P = 0.0051; 30 days-1 year, HRadj 1.28, 95% CI 0.98-1.67, P = 0.073] compared with those who stopped >1 year prior (P-trend = 0.0097). The benefit of ticagrelor depended on the time from last dose, with HRs (95% CI) for ticagrelor (pooled doses) vs. placebo of 0.73 (0.61-0.87), 0.86 (0.71-1.04), and 1.01 (0.80-1.27), respectively, by category (P-trend for interaction < 0.001). The benefit in those ≤30 days of stopping was similar regardless of time from MI (<2 years, HR 0.73, 95% CI 0.60-0.89 vs. ≥2 years, HR 0.71, 95% CI 0.50-1.00). Conclusion The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and at least one additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y12 inhibition, when compared with patients who had proved themselves stable more than 2 years from their MI and off P2Y12 inhibitor therapy for more than a year. The increase in bleeding events with ticagrelor was similar regardless of this time interval. For clinicians considering a strategy of prolonged P2Y12 inhibitor therapy in high-risk patients, these data suggest greater benefit in the continuation of such therapy without interruption after MI, rather than re-initiating such therapy in patients who have remained stable for an extended period. Future analyses may help to clarify further the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy.

LanguageEnglish
Pages1133-1142
Number of pages10
JournalEuropean Heart Journal
Volume37
Issue number14
DOIs
Publication statusPublished - 7 Apr 2016

Keywords

  • Antiplatelet therapy
  • Coronary artery disease
  • Ischaemic risk
  • P2Y12 inhibition
  • Platelet inhibition
  • Secondary prevention
  • Ticagrelor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Bonaca, Marc P. ; Bhatt, Deepak L. ; Steg, P. Gabriel ; Storey, Robert F. ; Cohen, Marc ; Im, Kyungah ; Oude Ophuis, Ton ; Budaj, Andrej ; Goto, Shinya ; López-Sendón, José ; Diaz, Rafael ; Dalby, Anthony ; Van De Werf, Frans ; Ardissino, Diego ; Montalescot, Gilles ; Aylward, Philip ; Magnani, Giulia ; Jensen, Eva C. ; Held, Peter ; Braunwald, Eugene ; Sabatine, Marc S. / Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction : insights from PEGASUS-TIMI 54. In: European Heart Journal. 2016 ; Vol. 37, No. 14. pp. 1133-1142.
@article{79026bc1bb9648878f60b60cc034b45e,
title = "Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54",
abstract = "Aims Ticagrelor reduced major adverse cardiovascular event (MACE) by 15-16{\%} in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y12 inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of therapy. Methods and results Patients in PEGASUS-TIMI 54 were categorized by time from last P2Y12 inhibitor (days: ≤30, >30-360, >360). The risk of MACE and the efficacy of ticagrelor were compared across categories. In the placebo arm, patients who more recently stopped P2Y12 inhibitor therapy had a greater number of risk factors but still had a higher risk of MACE after multivariable adjustment [≤30 days, hazard ratio (HR)adj 1.47, 95{\%} confidence interval (CI) 1.12-1.93, P = 0.0051; 30 days-1 year, HRadj 1.28, 95{\%} CI 0.98-1.67, P = 0.073] compared with those who stopped >1 year prior (P-trend = 0.0097). The benefit of ticagrelor depended on the time from last dose, with HRs (95{\%} CI) for ticagrelor (pooled doses) vs. placebo of 0.73 (0.61-0.87), 0.86 (0.71-1.04), and 1.01 (0.80-1.27), respectively, by category (P-trend for interaction < 0.001). The benefit in those ≤30 days of stopping was similar regardless of time from MI (<2 years, HR 0.73, 95{\%} CI 0.60-0.89 vs. ≥2 years, HR 0.71, 95{\%} CI 0.50-1.00). Conclusion The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and at least one additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y12 inhibition, when compared with patients who had proved themselves stable more than 2 years from their MI and off P2Y12 inhibitor therapy for more than a year. The increase in bleeding events with ticagrelor was similar regardless of this time interval. For clinicians considering a strategy of prolonged P2Y12 inhibitor therapy in high-risk patients, these data suggest greater benefit in the continuation of such therapy without interruption after MI, rather than re-initiating such therapy in patients who have remained stable for an extended period. Future analyses may help to clarify further the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy.",
keywords = "Antiplatelet therapy, Coronary artery disease, Ischaemic risk, P2Y12 inhibition, Platelet inhibition, Secondary prevention, Ticagrelor",
author = "Bonaca, {Marc P.} and Bhatt, {Deepak L.} and Steg, {P. Gabriel} and Storey, {Robert F.} and Marc Cohen and Kyungah Im and {Oude Ophuis}, Ton and Andrej Budaj and Shinya Goto and Jos{\'e} L{\'o}pez-Send{\'o}n and Rafael Diaz and Anthony Dalby and {Van De Werf}, Frans and Diego Ardissino and Gilles Montalescot and Philip Aylward and Giulia Magnani and Jensen, {Eva C.} and Peter Held and Eugene Braunwald and Sabatine, {Marc S.}",
year = "2016",
month = "4",
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doi = "10.1093/eurheartj/ehv531",
language = "English",
volume = "37",
pages = "1133--1142",
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Bonaca, MP, Bhatt, DL, Steg, PG, Storey, RF, Cohen, M, Im, K, Oude Ophuis, T, Budaj, A, Goto, S, López-Sendón, J, Diaz, R, Dalby, A, Van De Werf, F, Ardissino, D, Montalescot, G, Aylward, P, Magnani, G, Jensen, EC, Held, P, Braunwald, E & Sabatine, MS 2016, 'Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54', European Heart Journal, vol. 37, no. 14, pp. 1133-1142. https://doi.org/10.1093/eurheartj/ehv531

Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction : insights from PEGASUS-TIMI 54. / Bonaca, Marc P.; Bhatt, Deepak L.; Steg, P. Gabriel; Storey, Robert F.; Cohen, Marc; Im, Kyungah; Oude Ophuis, Ton; Budaj, Andrej; Goto, Shinya; López-Sendón, José; Diaz, Rafael; Dalby, Anthony; Van De Werf, Frans; Ardissino, Diego; Montalescot, Gilles; Aylward, Philip; Magnani, Giulia; Jensen, Eva C.; Held, Peter; Braunwald, Eugene; Sabatine, Marc S.

In: European Heart Journal, Vol. 37, No. 14, 07.04.2016, p. 1133-1142.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction

T2 - European heart journal

AU - Bonaca, Marc P.

AU - Bhatt, Deepak L.

AU - Steg, P. Gabriel

AU - Storey, Robert F.

AU - Cohen, Marc

AU - Im, Kyungah

AU - Oude Ophuis, Ton

AU - Budaj, Andrej

AU - Goto, Shinya

AU - López-Sendón, José

AU - Diaz, Rafael

AU - Dalby, Anthony

AU - Van De Werf, Frans

AU - Ardissino, Diego

AU - Montalescot, Gilles

AU - Aylward, Philip

AU - Magnani, Giulia

AU - Jensen, Eva C.

AU - Held, Peter

AU - Braunwald, Eugene

AU - Sabatine, Marc S.

PY - 2016/4/7

Y1 - 2016/4/7

N2 - Aims Ticagrelor reduced major adverse cardiovascular event (MACE) by 15-16% in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y12 inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of therapy. Methods and results Patients in PEGASUS-TIMI 54 were categorized by time from last P2Y12 inhibitor (days: ≤30, >30-360, >360). The risk of MACE and the efficacy of ticagrelor were compared across categories. In the placebo arm, patients who more recently stopped P2Y12 inhibitor therapy had a greater number of risk factors but still had a higher risk of MACE after multivariable adjustment [≤30 days, hazard ratio (HR)adj 1.47, 95% confidence interval (CI) 1.12-1.93, P = 0.0051; 30 days-1 year, HRadj 1.28, 95% CI 0.98-1.67, P = 0.073] compared with those who stopped >1 year prior (P-trend = 0.0097). The benefit of ticagrelor depended on the time from last dose, with HRs (95% CI) for ticagrelor (pooled doses) vs. placebo of 0.73 (0.61-0.87), 0.86 (0.71-1.04), and 1.01 (0.80-1.27), respectively, by category (P-trend for interaction < 0.001). The benefit in those ≤30 days of stopping was similar regardless of time from MI (<2 years, HR 0.73, 95% CI 0.60-0.89 vs. ≥2 years, HR 0.71, 95% CI 0.50-1.00). Conclusion The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and at least one additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y12 inhibition, when compared with patients who had proved themselves stable more than 2 years from their MI and off P2Y12 inhibitor therapy for more than a year. The increase in bleeding events with ticagrelor was similar regardless of this time interval. For clinicians considering a strategy of prolonged P2Y12 inhibitor therapy in high-risk patients, these data suggest greater benefit in the continuation of such therapy without interruption after MI, rather than re-initiating such therapy in patients who have remained stable for an extended period. Future analyses may help to clarify further the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy.

AB - Aims Ticagrelor reduced major adverse cardiovascular event (MACE) by 15-16% in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y12 inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of therapy. Methods and results Patients in PEGASUS-TIMI 54 were categorized by time from last P2Y12 inhibitor (days: ≤30, >30-360, >360). The risk of MACE and the efficacy of ticagrelor were compared across categories. In the placebo arm, patients who more recently stopped P2Y12 inhibitor therapy had a greater number of risk factors but still had a higher risk of MACE after multivariable adjustment [≤30 days, hazard ratio (HR)adj 1.47, 95% confidence interval (CI) 1.12-1.93, P = 0.0051; 30 days-1 year, HRadj 1.28, 95% CI 0.98-1.67, P = 0.073] compared with those who stopped >1 year prior (P-trend = 0.0097). The benefit of ticagrelor depended on the time from last dose, with HRs (95% CI) for ticagrelor (pooled doses) vs. placebo of 0.73 (0.61-0.87), 0.86 (0.71-1.04), and 1.01 (0.80-1.27), respectively, by category (P-trend for interaction < 0.001). The benefit in those ≤30 days of stopping was similar regardless of time from MI (<2 years, HR 0.73, 95% CI 0.60-0.89 vs. ≥2 years, HR 0.71, 95% CI 0.50-1.00). Conclusion The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and at least one additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y12 inhibition, when compared with patients who had proved themselves stable more than 2 years from their MI and off P2Y12 inhibitor therapy for more than a year. The increase in bleeding events with ticagrelor was similar regardless of this time interval. For clinicians considering a strategy of prolonged P2Y12 inhibitor therapy in high-risk patients, these data suggest greater benefit in the continuation of such therapy without interruption after MI, rather than re-initiating such therapy in patients who have remained stable for an extended period. Future analyses may help to clarify further the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy.

KW - Antiplatelet therapy

KW - Coronary artery disease

KW - Ischaemic risk

KW - P2Y12 inhibition

KW - Platelet inhibition

KW - Secondary prevention

KW - Ticagrelor

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U2 - 10.1093/eurheartj/ehv531

DO - 10.1093/eurheartj/ehv531

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SP - 1133

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JO - European heart journal

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SN - 0195-668X

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