Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin

Kevin P. Bliden; Anand Singla; Martin G. Gesheff; Peter P. Toth; Ali Tabrizchi; Gordon Ens; Kirk Guyer; Mandeep Singh; Christopher J. Franzese; Dwight D. Stapleton; Udaya S. Tantry; Paul A. Gurbel

doi:10.1160/TH14-01-0094

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(02): 323-331
DOI: 10.1160/TH14-01-0094

Platelets and Blood Cells

Schattauer GmbH

Statin therapy and thromboxane generation in patients with coronary artery disease treated with high-dose aspirin

Kevin P. Bliden

¹Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA

,

Anand Singla

²Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

,

Martin G. Gesheff

¹Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA

,

Peter P. Toth

³Department of Preventative Cardiology, CGH Medical Center, Sterling, Illinois, USA

,

Ali Tabrizchi

¹Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA

,

Gordon Ens

¹Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA

,

Kirk Guyer

⁴Department of Chemistry, Indiana University South Bend, South Bend, Indiana, USA

,

Mandeep Singh

¹Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA

,

Christopher J. Franzese

¹Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA

,

Dwight D. Stapleton

⁵Department of Medicine, Guthrie/Robert Packer Hospital, Sayre, Pennsylvania, USA

,

Udaya S. Tantry

¹Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA

,

Paul A. Gurbel

¹Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA

› Author Affiliations

Abstract

Summary

Aspirin and statin therapy are mainstay treatments in patients with coronary artery disease (CAD). The relation between statin therapy, in vivo thromboxane (Tx) generation; a marker of inflammation, and blood thrombogenicity has never been explored. Urinary 11-dehydro (dh) TxB₂ was determined in patients with suspected CAD on 325 mg daily aspirin therapy prior to undergoing cardiac catheterisation (n=281). Thrombogenicity was estimated by thrombelastographic measurement of thrombin-induced platelet-fibrin clot strength (TIP-FCS) and lipids/lipoproteins were determined by vertical density gradient ultracentrifugation/ELISA. The influence of statin therapy and dose was analysed by the atorvastatin equivalent dose (5–10 mg, 20–40 mg, or 80 mg daily). Statin therapy (n=186) was associated with a dose-dependent reduction in urinary 11-dh TxB₂ (p=0.046) that was independent of LDL and apo B100 levels but was strongly related to TIP-FCS (p=0.006). By multivariate analysis, no statin therapy (n=95) and female gender were independently associated with high urinary 11-dh TxB₂ [OR=2.95 (0.1.57–5.50, p=0.0007); OR=2.25 (1.24–4.05, p=0.007)], respectively. In aspirin-treated patients, statin therapy was independently and inversely associated with inflammation in a dose-dependent manner. Elevated 11-dh TxB₂ was associated with a prothrombotic state indicated by high TIP-FCS. Our data suggest that measurement of urinary 11-dTxB₂ may be a useful method to optimise statin dosing in order to reduce thrombotic risk.

Keywords

Aspirin - statin - urinary 11-dehydrothromboxane B₂ - lipids - inflammation - coronary artery disease - platelets

Full Text

References

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