Reduced Thrombin Formation and Altered Fibrin Clot Properties Induced by Polyunsaturated Omega-3 Fatty Acids on Top of Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention (OMEGA-PCI Clot)

Objective-The goal of this study was to investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) are able to alter plasma fibrin clot properties and reduce thrombin formation in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI). Methods and Results-In an investigator-initiated, prospective, double-blind, placebo-controlled, randomized study, patients undergoing PCI who received standard pharmacotherapy were assigned to the treatment with 1 g/day n-3 PUFA (n=30) or placebo (n=24) for 1 month. Plasma fibrin clot permeability (K-s); lysis time (t(50%)); prothrombin fragment 1.2; and peak thrombin generation from automated thrombogram, 8-isoprostaglandin F-2 alpha (8-iso-PGF(2 alpha), an oxidative stress marker), and C-reactive protein were determined at baseline, 3 to 5 days after randomization, and 30 days after randomization. At baseline, both treatment groups did not differ significantly. A 1-month treatment with n-3 PUFA compared with placebo was associated with 15.3% higher K-s, indicating larger pores in the fibrin network (P=0.0005); 14.3% shorter t50%, indicating increased susceptibility to fibrinolysis (P < 0.0001); 33.8% lower prothrombin fragment 1.2 (P=0.0013); 13.4% lower peak thrombin generation (P=0.04); and 13.1% lower 8-iso-PGF(2 alpha) (P=0.009). Treatment with n-3 PUFA had no effect on fibrinogen and C-reactive protein. After 1 month of treatment, fibrinogen (r=-0.53, P < 0.0001), treatment assignment (r=0.29, P=0.006) and 8-iso-PGF(2 alpha) (r=-0.27, P=0.015) were independently associated with clot permeability (P < 0.0001, R-2=0.66). Conclusion-Adding n-3 PUFA to standard therapy in stable patients undergoing PCI significantly decreases thrombin formation and oxidative stress and favorably alters fibrin clot properties. These findings indicate novel antithrombotic effects induced by n-3 PUFA in humans. (Arterioscler Thromb Vasc Biol. 2011; 31: 1696-1702.)