TY - JOUR
T1 - Venous thrombosis associated with HMG-CoA reductase inhibitors
AU - Lippi, Giuseppe
AU - Favaloro, Emmanuel J
AU - Sanchis-Gomar, Fabian
N1 - Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
PY - 2013/7
Y1 - 2013/7
N2 - Among the various hypolipidemic drugs, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (also known as "statins") belong to a heterogeneous class of compounds, sharing an identical hypocholesterolemic effect that develops through direct inhibition of a rate-limiting step in endogenous cholesterol synthesis. Their mechanism of action entails competitive inhibition of HMG-CoA reductase. Several lines of evidence suggest that the pleiotropic effects of statins may also play a role in prevention of venous thrombosis, wherein hypercholesterolemic patients are characterized by enhanced thrombin generation, increased susceptibility to endothelial dysfunction and platelet hyperreactivity, so that limiting or counteracting the burden of one or more of these mechanisms would provide an effective means of prophylaxis. Plausible biological links can also be found between statin therapy and reduction of thrombotic risk, mainly targeting immune system, blood coagulation, endothelium, lipid metabolism, and inflammation. The earlier JUPITER (Justification for the Use of Statins in Primary Prevention) trial provided appealing evidence that the risk of venous thrombosis may be lowered by statins. The results of the following studies and those of recent meta-analyses have, however, questioned this assumption. Currently, it seems thereby cautious to conclude that the use of statins as part of the approach used for preventing venous thromboembolism appears unwarranted. This is due to the existence of controversial clinical evidence, to the large number of patients who would need to be treated to prevent one case of venous thrombosis, as well as to the tangible risk of side effects. More randomized and the larger studies are needed before definitive conclusions can be drawn.
AB - Among the various hypolipidemic drugs, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (also known as "statins") belong to a heterogeneous class of compounds, sharing an identical hypocholesterolemic effect that develops through direct inhibition of a rate-limiting step in endogenous cholesterol synthesis. Their mechanism of action entails competitive inhibition of HMG-CoA reductase. Several lines of evidence suggest that the pleiotropic effects of statins may also play a role in prevention of venous thrombosis, wherein hypercholesterolemic patients are characterized by enhanced thrombin generation, increased susceptibility to endothelial dysfunction and platelet hyperreactivity, so that limiting or counteracting the burden of one or more of these mechanisms would provide an effective means of prophylaxis. Plausible biological links can also be found between statin therapy and reduction of thrombotic risk, mainly targeting immune system, blood coagulation, endothelium, lipid metabolism, and inflammation. The earlier JUPITER (Justification for the Use of Statins in Primary Prevention) trial provided appealing evidence that the risk of venous thrombosis may be lowered by statins. The results of the following studies and those of recent meta-analyses have, however, questioned this assumption. Currently, it seems thereby cautious to conclude that the use of statins as part of the approach used for preventing venous thromboembolism appears unwarranted. This is due to the existence of controversial clinical evidence, to the large number of patients who would need to be treated to prevent one case of venous thrombosis, as well as to the tangible risk of side effects. More randomized and the larger studies are needed before definitive conclusions can be drawn.
KW - Humans
KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
KW - Hyperlipoproteinemia Type II/blood
KW - Hypolipidemic Agents/adverse effects
KW - Risk Assessment
KW - Risk Factors
KW - Venous Thrombosis/chemically induced
U2 - 10.1055/s-0033-1343892
DO - 10.1055/s-0033-1343892
M3 - Review article
C2 - 23629822
SN - 0094-6176
VL - 39
SP - 515
EP - 532
JO - Seminars in Thrombosis and Hemostasis
JF - Seminars in Thrombosis and Hemostasis
IS - 5
ER -