American Journal of Cardiology
Volume 104, Issue 12 , Pages 1618-1623 , 15 December 2009

Effect of Atorvastatin on Platelet Thromboxane A2 Synthesis in Aspirin-Treated Patients With Acute Myocardial Infarction

  • M. Teresa Santos, PhD

      Affiliations

    • Research Center, University Hospital La Fe, Valencia, Spain
    • Corresponding Author InformationCorresponding author: Tel: (+34) 96-386-2700, ext. 50895; fax: (+34) 96-197-3018
    • Drs. Santos and Valles contributed equally to this article.
    • ,
  • M. Paz Fuset, MD

      Affiliations

    • Intensive Care Unit, University Hospital La Fe, Valencia, Spain
    • ,
  • Miguel Ruano, MD

      Affiliations

    • Intensive Care Unit, University Hospital La Fe, Valencia, Spain
    • ,
  • Antonio Moscardó, PhD

      Affiliations

    • Research Center, University Hospital La Fe, Valencia, Spain
    • ,
  • Juana Valles, PhD

      Affiliations

    • Research Center, University Hospital La Fe, Valencia, Spain
    • Drs. Santos and Valles contributed equally to this article.

Received 28 May 2009 ,Revised 26 July 2009 ,Accepted 26 July 2009.

References 

  1. Valles J, Santos MT, Fuset MP, Moscardo A, Ruano M, Perez F, et al. Partial inhibition of platelet thromboxane A2 synthesis by aspirin is associated with myonecrosis in patients with ST-Segment elevation myocardial infarction. Am J Cardiol. 2007;99:19–25
  2. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285:1711–1718
  3. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–1504
  4. Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G, et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007;49:1272–1278
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  10. Davi G, Averna M, Catalano I, Barbagallo C, Ganci A, Notarbartolo A, et al. Increased thromboxane biosynthesis in type IIa hypercholesterolemia. Circulation. 1992;85:1792–1798
  11. Notarbartolo A, Davi G, Averna M, Barbagallo CM, Ganci A, Giammarresi C, et al. Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1995;15:247–251
  12. Eikelboom JW, Hankey GJ, Thom J, Bhatt DL, Steg PG, Montalescot G, et al. Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid: determinants and effect on cardiovascular risk. Circulation. 2008;118:1705–1712
  13. Santos MT, Valles J, Marcus AJ, Safier LB, Broekman MJ, Islam N, et al. Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. J Clin Invest. 1991;87:571–580
  14. Valles J, Santos MT, Aznar J, Martinez M, Moscardo A, Pinon M, et al. Platelet-erythrocyte interactions enhance alpha(IIb)beta(3) integrin receptor activation and P-selectin expression during platelet recruitment: down-regulation by aspirin ex vivo. Blood. 2002;99:3978–3984
  15. Santos MT, Valles J, Lago A, Tembl J, Sanchez E, Moscardo A, et al. Residual platelet thromboxane A2 and prothrombotic effects of erythrocytes are important determinants of aspirin resistance in patients with vascular disease. Thromb Haemostas. 2008;6:615–621
  16. Valles J, Santos MT, Aznar J, Marcus AJ, Martinez-Sales V, Portoles M, et al. Erythrocytes metabolically enhance collagen-induced platelet responsiveness via increased thromboxane production, ADP release, and recruitment. Blood. 1991;78:154–162
  17. Valles J, Santos MT, Aznar J, Osa A, Lago A, Cosin J, et al. Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity. Circulation. 1998;97:350–355
  18. Santos MT, Moscardó A, Vallés J, Martinez M, Piñón M, Aznar J, et al. Participation of tyrosine phosphorylation in cytoskeletal reorganization, alphaIIbbeta3 integrin receptor activation and aspirin-insensitive mechanisms of thrombin-stimulated human platelets. Circulation. 2000;102:1924–1930
  19. Osamah H, Mira R, Sorina S, Shlomo K, Michael A. Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to the platelets. Br J Clin Pharmacol. 1997;44:77–83
  20. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S). Lancet. 1994;344:1383–1389
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  22. Niccoli G, Giubilato S, Russo E, Spaziani C, Leo A, Porto I, et al. Plasma levels of thromboxane A2 on admission are associated with no-reflow after primary percutaneous coronary intervention. Eur Heart J. 2008;29:1843–1850

 This study was supported in part by grants PI07/0463 and RENEVAS RD06/0026 from the Spanish Fondo de Investigaciones Sanitarias del Ministerio de Sanidad y Consumo (FIS), Madrid, Spain, and the Fundación Mutua Madrileña, Madrid, Spain, and Fundación para la Investigación Hospital La Fe, Valencia, Spain (to M.P. Fuset).

PII: S0002-9149(09)01470-2

doi: 10.1016/j.amjcard.2009.07.039

American Journal of Cardiology
Volume 104, Issue 12 , Pages 1618-1623 , 15 December 2009

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