Low-intensity warfarin reduces thrombin generation and fibrin turnover, but not low-grade inflammation, in men at risk of myocardial infarction.

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.