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 IIb/IIIa 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 IIb/IIIa 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.

• Authors: Tullio Palmerini, Sorin J Brener, Roxana Mehran, George Dangas, Philippe Genereux, Diego Della Riva, Andrea Mariani, Ke Xu, Gregg W Stone
• Journal: Circulation. Cardiovascular interventions (Circ Cardiovasc Interv) Vol. 6 Issue 5 Pg. 518-26 (Oct 01 2013) ISSN: 1941-7632 [Electronic] United States
• PMID: 24084625 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hirudins
• Integrin beta3
• Peptide Fragments
• Platelet Membrane Glycoprotein IIb
• Recombinant Proteins
• Heparin
• bivalirudin

Topics

• Acute Disease
• Aged
• Electrocardiography
• Female
• Follow-Up Studies
• Hemorrhage (etiology, prevention & control)
• Heparin (administration & dosage)
• Hirudins (administration & dosage, adverse effects)
• Humans
• Integrin beta3 (metabolism)
• Leukocyte Count
• Male
• Middle Aged
• Myocardial Infarction (complications, drug therapy, mortality)
• Peptide Fragments (administration & dosage, adverse effects)
• Platelet Membrane Glycoprotein IIb (metabolism)
• Prospective Studies
• Recombinant Proteins (administration & dosage, adverse effects)
• Survival Analysis