Does low-intensity warfarin reduce thrombin generation, fibrin turnover, and inflammation in men at risk of myocardial infarction?
The clinical benefit of low-intensity warfarin in preventing coronary events is associated with reduced thrombin generation and fibrin turnover, but not with changes in low-grade inflammation.
In the Thrombosis Prevention Trial (TPT), low-intensity warfarin reduced the risk of first coronary events only when the achieved international normalized ratio (INR) was > or =1.4. To validate the likely mechanism of action of low-intensity warfarin we measured its effects on plasma markers of thrombin generation, fibrin turnover and low-grade inflammation in TPT participants. D-dimer and prothrombin fragment F1.2 levels were lower at INRs > or =1.4 (P = 0.02 and 0.03 respectively); levels fell as INR increased (P for trend 0.04 and 0.002 respectively). C-reactive protein did not vary with INR. The efficacy of warfarin is related to reductions in thrombin generation and fibrin turnover.
MacCallum et al. (2004) studied this question.