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

Research output: Contribution to journalArticlepeer-review

Abstract

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 (TIPFCS) 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 dosedependent 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.

Original languageEnglish (US)
Pages (from-to)323-331
Number of pages9
JournalThrombosis and Haemostasis
Volume112
Issue number2
DOIs
StatePublished - 2014

Keywords

  • Aspirin
  • Coronary artery disease
  • Inflammation
  • Lipids
  • Platelets
  • Statin

ASJC Scopus subject areas

  • Hematology

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