Recent large clinical trials have demonstrated that HMG-CoA reductase 
inhibitors, or statins, markedly reduce morbidity and mortality when used in the 
primary and secondary prevention of cardiovascular disease. It has been 
established that the benefits of statin therapy in cardiovascular disease can be 
explained not only by the lipid-lowering potential of statins but also by 
nonlipid-related mechanisms (so-called "pleiotropic effects") that contribute to 
the positive effect of statins on the incidence of cardiovascular events. The 
coagulation and fibrinolytic systems are two separate but reciprocally linked 
enzyme cascades that regulate the formation and breakdown of fibrin. Numerous 
studies have demonstrated that disturbances of coagulation and fibrinolysis 
contribute to the development and progression of atherosclerosis, and that they 
affect the incidence of atherosclerosis-related clinical events. High plasma 
levels or activities of fibrinogen, factor VII, factor VIII, von Willebrand 
factor (vWF), soluble thrombomodulin, tissue plasminogen activator (tPA) and 
plasminogen activator inhibitor-1 (PAI-1) are thought to be associated with 
increased morbidity and mortality related to cardiovascular disease. 
Experimental studies and many clinical studies have recently shown that statins 
produce favourable effects on haemostatic parameters, including those that are 
risk factors for cardiovascular disease. Statins diminish procoagulant activity, 
which is observed at different stages of the coagulation cascade, including 
tissue factor (TF) activity, conversion of prothrombin to thrombin and thrombin 
activity. In some studies, statins also reduced fibrinogen levels. By altering 
the levels and activities of tPA and PAI-1, statins seem to stimulate 
fibrinolysis. The data on the effects of combined treatment with statins and 
other drugs on haemostasis are rather limited. They suggest that statins 
combined with fibric acid derivatives, omega-3 fatty acids and 17beta-estradiol 
are superior to statins alone. The only two clinical studies performed in 
patients with acute coronary syndromes showed a relatively weak effect of 
statins on haemostasis in those patients. Although various statins may produce 
different effects on individual variables, there are no convincing data showing 
that differences in their physicochemical and pharmacokinetic properties 
significantly alter their net effect on excessive procoagulant activity. Apart 
from the lipid-lowering effect, statins suppress the synthesis of several 
important nonsterol isoprenoids derived from the mevalonate pathway, especially 
farnesyl and geranylgeranyl pyrophosphates, which via enhanced protein 
prenylation, are involved in the regulation of many cellular processes. It is 
presumed that the inhibitory effect of statins on the mevalonate pathway is 
involved in the regulation of some key steps of coagulation and fibrinolysis 
processes. In this way they probably regulate the synthesis of TF, tPA and 
PAI-1, and perhaps they also control the generation and activity of thrombin. 
The beneficial effects of statins on coagulation and fibrinolysis may be 
responsible for their ability to decrease the number of cardiovascular events. 
The lipid-independent effects of statins on haemostasis may contribute to the 
marked decrease in the incidence rates of mortality, hospitalisation and 
revascularisation in patients treated with these drugs.