Leukocyte count is a modulating factor for the mortality benefit of bivalirudin in st-segment-elevation acute myocardial infarction the horizons-ami trial

Tullio Palmerini, Sorin J. Brener, Roxana Mehran, George Dangas, Philippe Genereux, Diego Della Riva, Andrea Mariani, Ke Xu, Gregg W. Stone

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background-Although the reduction in mortality with bivalirudin compared with unfractionated heparin plus glycoprotein 2b/3a inhibitors in the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial has been attributed to lower rates of major bleeding, alternative mechanisms have not been investigated in depth. We sought to investigate whether there might be an interaction between white blood cell (WBC) count and bivalirudin for the risk of mortality, and whether this interaction is independent of major bleeding. Methods and Results-Among the 3602 patients enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3%) patients. Patients were stratified according to WBC tertiles. At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with unfractionated heparin plus glycoprotein 2b/3a inhibitors in patients in the upper WBC tertile (all-cause death: 4.1% versus 9.3%, respectively; P=0.0004; cardiac death: 2.0% versus 6.9%; respectively; P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles. The reduction of mortality with bivalirudin across WBC tertiles was independent of major bleeding, and a significant interaction was apparent for 1-year all-cause mortality and cardiac mortality between WBC and bivalirudin therapy. Similar findings were apparent at 3 years. Conclusions-In patients with ST-segment-elevation myocardial infarction, a significant interaction between bivalirudin therapy and admission WBC count was apparent for 1-year mortality. The reduction in mortality was independent of major bleeding, suggesting that other mechanisms may be implicated in the survival benefit observed with bivalirudin. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Original languageEnglish (US)
Pages (from-to)518-526
Number of pages9
JournalCirculation: Cardiovascular Interventions
Volume6
Issue number5
DOIs
StatePublished - Oct 1 2013

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Leukocyte Count
Myocardial Infarction
Mortality
Leukocytes
Hemorrhage
Stents
Heparin
Glycoproteins
bivalirudin
Cell- and Tissue-Based Therapy
Cause of Death
Clinical Trials
Survival

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Palmerini, Tullio ; Brener, Sorin J. ; Mehran, Roxana ; Dangas, George ; Genereux, Philippe ; Riva, Diego Della ; Mariani, Andrea ; Xu, Ke ; Stone, Gregg W. / Leukocyte count is a modulating factor for the mortality benefit of bivalirudin in st-segment-elevation acute myocardial infarction the horizons-ami trial. In: Circulation: Cardiovascular Interventions. 2013 ; Vol. 6, No. 5. pp. 518-526.
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title = "Leukocyte count is a modulating factor for the mortality benefit of bivalirudin in st-segment-elevation acute myocardial infarction the horizons-ami trial",
abstract = "Background-Although the reduction in mortality with bivalirudin compared with unfractionated heparin plus glycoprotein 2b/3a inhibitors in the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial has been attributed to lower rates of major bleeding, alternative mechanisms have not been investigated in depth. We sought to investigate whether there might be an interaction between white blood cell (WBC) count and bivalirudin for the risk of mortality, and whether this interaction is independent of major bleeding. Methods and Results-Among the 3602 patients enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3{\%}) patients. Patients were stratified according to WBC tertiles. At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with unfractionated heparin plus glycoprotein 2b/3a inhibitors in patients in the upper WBC tertile (all-cause death: 4.1{\%} versus 9.3{\%}, respectively; P=0.0004; cardiac death: 2.0{\%} versus 6.9{\%}; respectively; P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles. The reduction of mortality with bivalirudin across WBC tertiles was independent of major bleeding, and a significant interaction was apparent for 1-year all-cause mortality and cardiac mortality between WBC and bivalirudin therapy. Similar findings were apparent at 3 years. Conclusions-In patients with ST-segment-elevation myocardial infarction, a significant interaction between bivalirudin therapy and admission WBC count was apparent for 1-year mortality. The reduction in mortality was independent of major bleeding, suggesting that other mechanisms may be implicated in the survival benefit observed with bivalirudin. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.",
author = "Tullio Palmerini and Brener, {Sorin J.} and Roxana Mehran and George Dangas and Philippe Genereux and Riva, {Diego Della} and Andrea Mariani and Ke Xu and Stone, {Gregg W.}",
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Leukocyte count is a modulating factor for the mortality benefit of bivalirudin in st-segment-elevation acute myocardial infarction the horizons-ami trial. / Palmerini, Tullio; Brener, Sorin J.; Mehran, Roxana; Dangas, George; Genereux, Philippe; Riva, Diego Della; Mariani, Andrea; Xu, Ke; Stone, Gregg W.

In: Circulation: Cardiovascular Interventions, Vol. 6, No. 5, 01.10.2013, p. 518-526.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Leukocyte count is a modulating factor for the mortality benefit of bivalirudin in st-segment-elevation acute myocardial infarction the horizons-ami trial

AU - Palmerini, Tullio

AU - Brener, Sorin J.

AU - Mehran, Roxana

AU - Dangas, George

AU - Genereux, Philippe

AU - Riva, Diego Della

AU - Mariani, Andrea

AU - Xu, Ke

AU - Stone, Gregg W.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Background-Although the reduction in mortality with bivalirudin compared with unfractionated heparin plus glycoprotein 2b/3a inhibitors in the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial has been attributed to lower rates of major bleeding, alternative mechanisms have not been investigated in depth. We sought to investigate whether there might be an interaction between white blood cell (WBC) count and bivalirudin for the risk of mortality, and whether this interaction is independent of major bleeding. Methods and Results-Among the 3602 patients enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3%) patients. Patients were stratified according to WBC tertiles. At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with unfractionated heparin plus glycoprotein 2b/3a inhibitors in patients in the upper WBC tertile (all-cause death: 4.1% versus 9.3%, respectively; P=0.0004; cardiac death: 2.0% versus 6.9%; respectively; P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles. The reduction of mortality with bivalirudin across WBC tertiles was independent of major bleeding, and a significant interaction was apparent for 1-year all-cause mortality and cardiac mortality between WBC and bivalirudin therapy. Similar findings were apparent at 3 years. Conclusions-In patients with ST-segment-elevation myocardial infarction, a significant interaction between bivalirudin therapy and admission WBC count was apparent for 1-year mortality. The reduction in mortality was independent of major bleeding, suggesting that other mechanisms may be implicated in the survival benefit observed with bivalirudin. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

AB - Background-Although the reduction in mortality with bivalirudin compared with unfractionated heparin plus glycoprotein 2b/3a inhibitors in the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial has been attributed to lower rates of major bleeding, alternative mechanisms have not been investigated in depth. We sought to investigate whether there might be an interaction between white blood cell (WBC) count and bivalirudin for the risk of mortality, and whether this interaction is independent of major bleeding. Methods and Results-Among the 3602 patients enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3%) patients. Patients were stratified according to WBC tertiles. At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with unfractionated heparin plus glycoprotein 2b/3a inhibitors in patients in the upper WBC tertile (all-cause death: 4.1% versus 9.3%, respectively; P=0.0004; cardiac death: 2.0% versus 6.9%; respectively; P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles. The reduction of mortality with bivalirudin across WBC tertiles was independent of major bleeding, and a significant interaction was apparent for 1-year all-cause mortality and cardiac mortality between WBC and bivalirudin therapy. Similar findings were apparent at 3 years. Conclusions-In patients with ST-segment-elevation myocardial infarction, a significant interaction between bivalirudin therapy and admission WBC count was apparent for 1-year mortality. The reduction in mortality was independent of major bleeding, suggesting that other mechanisms may be implicated in the survival benefit observed with bivalirudin. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

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