Effects of polyunsaturated omega-3 fatty acids on responsiveness to dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: the OMEGA-PCI (OMEGA-3 fatty acids after pci to modify responsiveness to dual antiplatelet therapy) study.
OBJECTIVE
The purpose of this study was to investigate whether omega-3 polyunsaturated fatty acids (PUFAs) are able to modify platelet responsiveness to dual antiplatelet therapy in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI).


BACKGROUND
Although previous studies have suggested antiplatelet properties of omega-3 polyunsaturated fatty acids, it is unknown whether they can enhance platelet inhibition on standard aspirin and clopidogrel treatment.


METHODS
The OMEGA-PCI (OMEGA-3 Fatty Acids After PCI to Modify Responsiveness to Dual Antiplatelet Therapy) study was an investigator-initiated, prospective, single-center, double-blind, placebo-controlled, randomized study. Patients receiving standard dual antiplatelet therapy (aspirin 75 mg/day and clopidogrel 600 mg loading dose followed by 75 mg/day) were randomly assigned to receive the addition of 1 g of omega-3 ethyl esters (n = 33) or placebo (n = 30) for 1 month. Platelet function was measured serially by light transmission aggregometry (adenosine diphosphate and arachidonic acid [AA] were used as agonists) and assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein at baseline, 12 h, 3 to 5 days, and 30 days after randomization.


RESULTS
The P2Y(12) reactivity index was significantly lower, by 22.2%, after 1 month of treatment with omega-3 polyunsaturated fatty acids compared with placebo when used in addition to dual antiplatelet therapy (p = 0.020). Maximal platelet aggregation induced by 5 and 20 micromol/l adenosine diphosphate was lower by 13.3% (p = 0.026) and 9.8% (p = 0.029), respectively, after 1 month of treatment with omega-3 polyunsaturated fatty acids compared with placebo. Platelet aggregation after AA stimulation was low and did not change significantly throughout the study. There were no cases of aspirin resistance during follow-up that was suggestive of good compliance with the medication.


CONCLUSIONS
The addition of omega-3 ethyl esters to the combination of aspirin and clopidogrel significantly potentiates platelet response to clopidogrel after percutaneous coronary intervention.
Gajos
Grzegorz
G
Department of Coronary Disease, John Paul II Hospital, Cracow, Poland. ggajos@szpitaljp2.krakow.pl
Rostoff
Pawel
P
Undas
Anetta
A
Piwowarska
Wiesława
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D001798:Blood Proteins; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010976:Platelet Count; D011379:Prognosis; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D015525:Fatty Acids, Omega-3; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin