Analysis of platelet α2-adrenergic receptor activity in stable coronary artery disease patients on dual antiplatelet therapy

Bernát János Béres; Emese Tóth-Zsámboki; Katarína Vargová; Ádám László; Tamás Masszi; Gábor Kerecsen; István Préda; Róbert Gábor Kiss

doi:10.1160/TH08-03-0158

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(05): 829-838
DOI: 10.1160/TH08-03-0158

Platelets and Blood Cells

Schattauer GmbH

Analysis of platelet α2-adrenergic receptor activity in stable coronary artery disease patients on dual antiplatelet therapy

Bernát János Béres^*

¹Research Group for Inflammation Biology and Immunogenomics of Hungarian Academy of Sciences and Semmelweis University Budapest, Hungary

,

Emese Tóth-Zsámboki^*

¹Research Group for Inflammation Biology and Immunogenomics of Hungarian Academy of Sciences and Semmelweis University Budapest, Hungary

²State Health Center, Department of Cardiology, Budapest, Hungary

,

Katarína Vargová

¹Research Group for Inflammation Biology and Immunogenomics of Hungarian Academy of Sciences and Semmelweis University Budapest, Hungary

,

Ádám László

³Szent László Hospital, Department of Bone Marrow Transplantation, Budapest, Hungary

,

Tamás Masszi

³Szent László Hospital, Department of Bone Marrow Transplantation, Budapest, Hungary

,

Gábor Kerecsen

²State Health Center, Department of Cardiology, Budapest, Hungary

,

István Préda

¹Research Group for Inflammation Biology and Immunogenomics of Hungarian Academy of Sciences and Semmelweis University Budapest, Hungary

²State Health Center, Department of Cardiology, Budapest, Hungary

,

Róbert Gábor Kiss

¹Research Group for Inflammation Biology and Immunogenomics of Hungarian Academy of Sciences and Semmelweis University Budapest, Hungary

²State Health Center, Department of Cardiology, Budapest, Hungary

› Author Affiliations

Abstract

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Summary

Combined antiplatelet therapy reduces recurrent atherothrombotic events in stable coronary disease patients; however, high residual platelet reactivity measured ex vivo still raises concerns as a condition related to treatment failure. Alpha-2 adrenoceptor enhances platelet reactivity and might contribute to this phenomenon. For the present study, 121 stable angina patients on standard dual antiplatelet therapy (75 mg clopidogrel and 100 mg acetylsalicylic acid) were recruited. Born aggregometry was performed with adenosine diphosphate (ADP),collagen and epnephrine. To verify platelet adrenergic activity, potentiation by low-dose epinephrine and inhibition by selective alpha-2 receptor blocker atipamezole were determined. To assess the P2Y₁₂-specific residual activity, cangrelor was used. Plasma norepinephrine, soluble CD40-ligand, high-sensitivity-C-reactive protein (hsCRP) - and in 24 subjects platelet P-selectin positivity were measured. Epinephrine - at very low concentration (10^-9g/ml) - significantly potentiates (1.25 µM ADP: 26.5% vs. 43%; 5 µM ADP: 53% vs. 64.5%; collagen: 17% vs 42%, p<0.001) while atipamezole inhibits ADP- and collagen-induced platelet aggregations (1.25 µM ADP: 26.5% vs. 23%; 5 µM ADP: 53% vs. 47%;collagen:17% vs.11%,p<0.001).Patients with high adrenergic activity have significantly increased baseline ADP- and collagen-induced platelet aggregation. Based on cangrelor’s efficacy, these patients have significantly more residual P2Y₁₂ activity as well.HsCRP and soluble CD40-ligand levels were similar.In conclusion, stable coronary heart disease patients with prominent adrenoceptor activity in vitro have significantly increased platelet aggregability and more functional P2Y₁₂ receptor, indicating poor inhibitory response to thienopyridines.Therefore,platelet adrenergic receptor represents a considerable, dynamic factor of high residual platelet reactivity and might contribute to cardiovascular events indicating failure of antiplatelet therapy.

Keywords

Antiplatelet agents - cardiology - platelet physiology - receptors

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References

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