Effects of simvastatin on tissue factor pathway of blood coagulation in STATCOPE (Simvastatin in the prevention of COPD exacerbations) trial

Statins are widely used to lower lipids and reduce cardiovascular events. In vitro studies and small studies in patients with hyperlipidemias show statins inhibit tissue factor (TF) and blood coagulation mechanisms. We assessed the effects of simvastatin on TF and coagulation biomarkers in patients entered in STATCOPE, a multicenter, randomized, placebo‐controlled trial of simvastatin (40 mg daily) versus placebo on exacerbation rates in patients with chronic obstructive pulmonary disease (COPD).

[1]  daran teilhaben,et al.  Whole , 2020, Definitions.

[2]  J. Cardoso,et al.  COPD and Cardiovascular Disease. , 2019, Pulmonology.

[3]  N. Mackman,et al.  Tissue Factor: An Essential Mediator of Hemostasis and Trigger of Thrombosis , 2018, Arteriosclerosis, thrombosis, and vascular biology.

[4]  U. Laufs,et al.  Pleiotropic Effects of Statins on the Cardiovascular System , 2017, Circulation research.

[5]  A. Mast.  Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein. , 2016, Arteriosclerosis, thrombosis, and vascular biology.

[6]  J. Hansen,et al.  COPD and risk of venous thromboembolism and mortality in a general population , 2015, European Respiratory Journal.

[7]  Meilan K. Han,et al.  Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. , 2014, The New England journal of medicine.

[8]  E. Akpınar,et al.  Incidence of pulmonary embolism during COPD exacerbation*, ** , 2014, Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia.

[9]  A. Folsom,et al.  Statin therapy and levels of hemostatic factors in a healthy population: the Multi‐Ethnic Study of Atherosclerosis , 2013, Journal of thrombosis and haemostasis : JTH.

[10]  B. Beghé,et al.  Exacerbation of respiratory symptoms in COPD patients may not be exacerbations of COPD , 2013, European Respiratory Journal.

[11]  C. Homko,et al.  Whole-Blood Tissue Factor Procoagulant Activity Is Elevated in Type 1 Diabetes , 2012, Diabetes Care.

[12]  D. Johns,et al.  Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin. , 2012, The Journal of clinical investigation.

[13]  J. Losa,et al.  Venous thromboembolism in COPD hospitalized patients , 2011, Journal of Thrombosis and Thrombolysis.

[14]  Krzysztof Sladek,et al.  Fibrin clot properties are altered in patients with chronic obstructive pulmonary disease , 2009, Thrombosis and Haemostasis.

[15]  G. Criner,et al.  Circulating tissue factor procoagulant activity is elevated in stable moderate to severe chronic obstructive pulmonary disease. , 2009, Thrombosis research.

[16]  J Shepherd,et al.  The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials , 2009, BMJ : British Medical Journal.

[17]  P. Libby,et al.  Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. , 2008, The New England journal of medicine.

[18]  T. Moua,et al.  COPD and PE: A clinical dilemma , 2008, International journal of chronic obstructive pulmonary disease.

[19]  C. Homko,et al.  Circulating tissue factor procoagulant activity and thrombin generation in patients with type 2 diabetes: effects of insulin and glucose. , 2007, The Journal of clinical endocrinology and metabolism.

[20]  J. Gaughan,et al.  Factor VIIa and tissue factor procoagulant activity in diabetes mellitus after acute ischemic stroke: Impact of hyperglycemia , 2007, Thrombosis and Haemostasis.

[21]  A. Szczeklik,et al.  Atorvastatin and quinapril inhibit blood coagulation in patients with coronary artery disease following 28 days of therapy , 2006, Journal of thrombosis and haemostasis : JTH.

[22]  Judith K Jones,et al.  Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. , 2006, Annals of epidemiology.

[23]  C. Homko,et al.  Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. , 2006, Diabetes.

[24]  K. Mann,et al.  Simvastatin given for 3 days can inhibit thrombin generation and activation of factor V and enhance factor Va inactivation in hypercholesterolemic patients. , 2005, Arteriosclerosis, Thrombosis and Vascular Biology.

[25]  A. Szczeklik,et al.  Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia , 2005, Thrombosis and Haemostasis.

[26]  M. Wolzt,et al.  Simvastatin Blunts Endotoxin-Induced Tissue Factor In Vivo , 2005, Circulation.

[27]  R. Lauro,et al.  Short-Term Treatment With Atorvastatin Reduces Platelet CD40 Ligand and Thrombin Generation in Hypercholesterolemic Patients , 2005, Circulation.

[28]  K. Mann,et al.  Statins and Blood Coagulation , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[29]  A. Palazzuoli,et al.  Different effect induced by treatment with several statins on monocyte tissue factor expression in hypercholesterolemic subjects , 2003, Clinical and Experimental Medicine.

[30]  V. Fuster,et al.  Role of Risk Factors in the Modulation of Tissue Factor Activity and Blood Thrombogenicity , 2003, Circulation.

[31]  K. Mann,et al.  Simvastatin Depresses Blood Clotting by Inhibiting Activation of Prothrombin, Factor V, and Factor XIII and by Enhancing Factor Va Inactivation , 2001, Circulation.

[32]  P. Libby,et al.  An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro , 2001, Circulation.

[33]  S. Basili,et al.  Inhibition of tissue-factor-mediated thrombin generation by simvastatin. , 2000, Atherosclerosis.

[34]  S. Ross,et al.  Clinical outcomes in statin treatment trials: a meta-analysis. , 1999, Archives of internal medicine.

[35]  J. Badimón,et al.  Blood-borne tissue factor: another view of thrombosis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[36]  C. Moertel,et al.  Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. , 1998, Blood.