Adding Omega-3 Fatty Acids to Dual Antiplatelet Therapy May Reduce Thrombotic Risk

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The addition of omega-3 polyunsaturated fatty acids—found in fish oil—to dual antiplatelet therapy decreases thrombin formation and favorably alters fibrin clot properties in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). The results, from a small study published online May 26, 2011, ahead of print in Arteriosclerosis, Thrombosis and Vascular Biology, suggest that the compound may have antithrombotic effects in humans.

In the double-blind OMEGA-PCI trial, 63 patients with stable CAD undergoing PCI and receiving dual antiplatelet therapy (aspirin 75 mg/day and 600-mg clopidogrel loading dose followed by 75 mg/day) were randomized to 1,000 mg of omega-3 polyunsaturated fatty acids or placebo once daily for 4 weeks. The study examined whether the fatty acids modified platelet responsiveness.

For the current prespecified subanalysis, known as OMEGA-PCI Clot, Anetta Undas, MD, PhD, of Jagiellonian University Medical College (Krakow, Poland), and colleagues assessed the effect of omega-3 fatty acids on fibrin clot permeability, thrombin generation, inflammation, and oxidative stress in 54 patients from the original study who had blood samples taken at baseline, 3 to 5 days after PCI, and at 1 month.

Fatty Acids Impart Manifold Effects

Baseline variables were similar between the 2 groups. By 1 month follow-up, several differences were seen in patients taking omega-3 fatty acids vs. placebo:

• 15.3% higher plasma fibrin clot permeability, indicating larger pores in the fibrin network (P = 0.0005)
• 14.3% shorter lysis time, 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)
• 13.1% lower 8-isoprostoglandin F_2α, a marker of oxidative stress (P = 0.009)

Fibrinogen, treatment assignment, and oxidative stress levels all were independently associated with clot permeability after 1 month of therapy.

However, no differences were found between the 2 groups for fibrinogen, C-reactive protein, and clotting Factor II and XIII levels.

The adverse events that occurred during the study were rated as mild, and their frequency did not differ significantly between groups. Similar proportions of patients in both groups reported minor bruising, which did not require medical intervention. There were no major cardiac adverse events during follow-up.

Small Exploratory Study

“We have demonstrated that clopidogrel added to aspirin in the placebo group does not influence thrombin generation, which is consistent with previous reports,” Dr. Undas and colleagues write. “Given the effect of clopidogrel on clots obtained from whole blood, our observations confirmed that blood cells and platelets are important contributors to thrombus characteristics.”

But while it appears that omega-3 fatty acids have novel antithrombotic effects, no clinical endpoints were evaluated to “establish whether the effect of [omega-3 polyunsaturated fatty acids] on fibrin structure and thrombin generation improved clinical outcomes during follow-up.” Therefore, a larger study will be needed to fully explore the effect, they advise.

The study authors also list several limitations to the study, including the small sample size and limited patient population. For those reasons, the results cannot be extrapolated to high-risk patients, such as those with acute coronary syndromes; healthy patients; or those who are not assigned dual antiplatelet therapy.

Study Details

All subjects asked to increase their consumption of oily fish. The use of non-steroidal anti-inflammatory drugs was discouraged.

 

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Source:
Gajos G, Zalewski J, Rostoff P, et al. 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). Arterioscler Thromb Vasc Biol. 2011;Epub ahead of print.

 

 

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