Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease

Marc P. Bonaca, Deepak L. Bhatt, Robert F. Storey, Ph Gabriel Steg, Marc Cohen, Julia Kuder, Erica Goodrich, José C. Nicolau, Alexander Parkhomenko, José López-Sendón, Mikael Dellborg, Anthony Dalby, Jindřich Špinar, Philip Aylward, Ramón Corbalán, Maria Teresa B Abola, Eva C. Jensen, Peter Held, Eugene Braunwald, Marc S. Sabatine

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Background Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). Objectives This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. Methods PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. Results A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026). Conclusions Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562)

LanguageEnglish
Pages2719-2728
Number of pages10
JournalJournal of the American College of Cardiology
Volume67
Issue number23
DOIs
Publication statusPublished - 2016

Keywords

  • acute limb ischemia
  • major adverse cardiovascular events
  • major adverse limb events
  • peripheral arterial disease
  • ticagrelor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Bonaca, Marc P. ; Bhatt, Deepak L. ; Storey, Robert F. ; Steg, Ph Gabriel ; Cohen, Marc ; Kuder, Julia ; Goodrich, Erica ; Nicolau, José C. ; Parkhomenko, Alexander ; López-Sendón, José ; Dellborg, Mikael ; Dalby, Anthony ; Špinar, Jindřich ; Aylward, Philip ; Corbalán, Ramón ; Abola, Maria Teresa B ; Jensen, Eva C. ; Held, Peter ; Braunwald, Eugene ; Sabatine, Marc S. / Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. In: Journal of the American College of Cardiology. 2016 ; Vol. 67, No. 23. pp. 2719-2728.
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abstract = "Background Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). Objectives This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. Methods PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. Results A total of 1,143 patients (5{\%}) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3{\%} vs. 8.4{\%}; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95{\%} confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0{\%} vs. 0.1{\%}) and peripheral revascularization procedures (9.15{\%} vs. 0.46{\%}). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1{\%} (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12{\%} (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95{\%} confidence interval: 0.44 to 0.95; p = 0.026). Conclusions Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562)",
keywords = "acute limb ischemia, major adverse cardiovascular events, major adverse limb events, peripheral arterial disease, ticagrelor",
author = "Bonaca, {Marc P.} and Bhatt, {Deepak L.} and Storey, {Robert F.} and Steg, {Ph Gabriel} and Marc Cohen and Julia Kuder and Erica Goodrich and Nicolau, {Jos{\'e} C.} and Alexander Parkhomenko and Jos{\'e} L{\'o}pez-Send{\'o}n and Mikael Dellborg and Anthony Dalby and Jindřich Špinar and Philip Aylward and Ram{\'o}n Corbal{\'a}n and Abola, {Maria Teresa B} and Jensen, {Eva C.} and Peter Held and Eugene Braunwald and Sabatine, {Marc S.}",
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Bonaca, MP, Bhatt, DL, Storey, RF, Steg, PG, Cohen, M, Kuder, J, Goodrich, E, Nicolau, JC, Parkhomenko, A, López-Sendón, J, Dellborg, M, Dalby, A, Špinar, J, Aylward, P, Corbalán, R, Abola, MTB, Jensen, EC, Held, P, Braunwald, E & Sabatine, MS 2016, 'Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease', Journal of the American College of Cardiology, vol. 67, no. 23, pp. 2719-2728. https://doi.org/10.1016/j.jacc.2016.03.524

Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease. / Bonaca, Marc P.; Bhatt, Deepak L.; Storey, Robert F.; Steg, Ph Gabriel; Cohen, Marc; Kuder, Julia; Goodrich, Erica; Nicolau, José C.; Parkhomenko, Alexander; López-Sendón, José; Dellborg, Mikael; Dalby, Anthony; Špinar, Jindřich; Aylward, Philip; Corbalán, Ramón; Abola, Maria Teresa B; Jensen, Eva C.; Held, Peter; Braunwald, Eugene; Sabatine, Marc S.

In: Journal of the American College of Cardiology, Vol. 67, No. 23, 2016, p. 2719-2728.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease

AU - Bonaca, Marc P.

AU - Bhatt, Deepak L.

AU - Storey, Robert F.

AU - Steg, Ph Gabriel

AU - Cohen, Marc

AU - Kuder, Julia

AU - Goodrich, Erica

AU - Nicolau, José C.

AU - Parkhomenko, Alexander

AU - López-Sendón, José

AU - Dellborg, Mikael

AU - Dalby, Anthony

AU - Špinar, Jindřich

AU - Aylward, Philip

AU - Corbalán, Ramón

AU - Abola, Maria Teresa B

AU - Jensen, Eva C.

AU - Held, Peter

AU - Braunwald, Eugene

AU - Sabatine, Marc S.

PY - 2016

Y1 - 2016

N2 - Background Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). Objectives This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. Methods PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. Results A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026). Conclusions Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562)

AB - Background Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). Objectives This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. Methods PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin—Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. Results A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026). Conclusions Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562)

KW - acute limb ischemia

KW - major adverse cardiovascular events

KW - major adverse limb events

KW - peripheral arterial disease

KW - ticagrelor

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U2 - 10.1016/j.jacc.2016.03.524

DO - 10.1016/j.jacc.2016.03.524

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