Selective COX-2 inhibitors increase the risk of myocardial infarction andstroke that is attributed to their ability to inhibit prostacyclin (PGI(2)), lipoxins, resolvins, andendothelial nitric oxide (eNO) but not platelet COX-1 derived thromboxane A(2) (TXA(2)). In contrast,aspirin blocks both COX-1 and COX-2 enzymes that, in turn, increases intracellular concentrations ofdihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoicacid (DHA) and reduced formation of eicosanoids. On the other hand, such an increase is much less withspecific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway.DGLA, AA and EPA form precursors to PGE(1) , PGI(2), and PGI(3) respectively, which are potent vasodilatorsand platelet anti-aggregators, and thus aid in the prevention of thrombus formation. EPA has anti-arrhythmicaction, and EPA, DHA (docosahexaenoic acid), DGLA, and PGE(1) have anti-inflammatory actions as well.EPA, DHA, and AA augment eNO formation that has anti-atherosclerotic action. Hence, combining EFAs withCOX-2 inhibitors will prevent thrombotic cardiovascular events.

Keywords: Epoprostenol - antagonists & inhibitors, Epoprostenol - metabolism, Anti-Inflammatory Agents, Non-Steroidal - pharmacology, Aspirin - pharmacology, Cardiovascular Diseases - metabolism, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors - pharmacology, Eicosanoids - biosynthesis, Epoprostenol - metabolism, Fatty Acids, Essential - metabolism, Membrane Proteins, Prostaglandin-Endoperoxide Synthases - metabolism