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
1   Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA
,
Anand Singla
2   Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
,
Martin G. Gesheff
1   Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA
,
Peter P. Toth
3   Department of Preventative Cardiology, CGH Medical Center, Sterling, Illinois, USA
,
Ali Tabrizchi
1   Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA
,
Gordon Ens
1   Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA
,
Kirk Guyer
4   Department of Chemistry, Indiana University South Bend, South Bend, Indiana, USA
,
Mandeep Singh
1   Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA
,
Christopher J. Franzese
1   Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA
,
Dwight D. Stapleton
5   Department of Medicine, Guthrie/Robert Packer Hospital, Sayre, Pennsylvania, USA
,
Udaya S. Tantry
1   Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA
,
Paul A. Gurbel
1   Sinai Center for Thrombosis Research, Sinai Hospital, Baltimore, Maryland, USA
› Author Affiliations
Further Information

Publication History

Received: 30 January 2014

Accepted after major revision: 03 March 2014

Publication Date:
04 December 2017 (online)

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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.