The lack of aspirin resistance in patients with coronary artery disease

Abstract

BackgroundAspirin resistance established by different laboratory methods is still a debated problem. Using COX1 specific methods no aspirin resistance was detected among healthy volunteers. Here we tested the effect of chronic aspirin treatment on platelets from patients with stable coronary artery disease. The expression of COX2 mRNA in platelets and its influences on the effect of aspirin was also investigated.MethodsOne hundred and forty four patients were enrolled in the study. The direct measurement of COX1 acetylation was carried out by monoclonal antibodies specific to acetylated and non-acetylated COX1 (acCOX1 and nacCOX1) using Western blotting technique. Arachidonic acid (AA) induced TXB2 production by platelets was measured by competitive immunoassay. AA induced platelet aggregation, ATP secretion and VerifyNow Aspirin Assay were also performed. COX2 and COX1 mRNA expression in platelets were measured in 56 patients by RT-qPCR.ResultsIn 138 patients only acCOX1 was detected, in the remaining six patients nacCOX1 disappeared after a compliance period. AA induced TXB2 production by platelets was very low in all patients including the 6 patients after compliance. AA induced platelet aggregation, secretion and with a few exceptions the VerifyNow Assay also demonstrated the effect of aspirin. Smoking, diabetes mellitus and inflammatory conditions did not influence the results. The very low amount of COX2 mRNA detected in 39 % of the investigated platelets did not influence the effect of aspirin.ConclusionsNo aspirin resistance was detected among patients with stable coronary artery disease. COX2 expression in platelets did not influence the effect of aspirin.

Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long‐Term Outcome After Cardiac Surgery

“…4,7,8 Although initially assumed to be attributable to the failure of aspirin to inhibit platelet COX-1-mediated thromboxane generation and consequent platelet activation, it is now recognized that aspirin is efficient at inhibiting platelet COX-1 and that much of the residual TXA 2 generation in patients taking aspirin originates from nonplatelet sources. [26][27][28] A unique feature of our analysis was that it only included subjects in whom inhibition of platelet thromboxane generation was verified, conclusively demonstrating that TXA 2 originating from nonplatelet tissue adversely affects clinical outcome and survival. Sources of nonplatelet TXA 2 generation have not been conclusively identified and may conceivably vary depending on the patient population and conditions under study.…”

“…Studies have emerged in recent years demonstrating that persistent TXA 2 generation in patients with cardiovascular disease undergoing aspirin therapy predicts an increased risk of atherothrombosis and death . Although initially assumed to be attributable to the failure of aspirin to inhibit platelet COX‐1–mediated thromboxane generation and consequent platelet activation, it is now recognized that aspirin is efficient at inhibiting platelet COX‐1 and that much of the residual TXA 2 generation in patients taking aspirin originates from nonplatelet sources . A unique feature of our analysis was that it only included subjects in whom inhibition of platelet thromboxane generation was verified, conclusively demonstrating that TXA 2 originating from nonplatelet tissue adversely affects clinical outcome and survival.…”

Dosage forms and doses of acetylsalicylic acid: significance for clinical practice

“…Неэф фективность АСК для профилактики острых сердечнососудистых событий у таких пациентов часто считается проявлением резистент ности к аспирину, хотя это вероятно связано с тем, что АСК избирательно подавляет только один из нескольких путей, ведущих к активации тромбоцитов [45]. Например, он не ингибирует активацию тромбоцитов, вызванную силь ными агонистами [46]. Более 20 лет назад Di Minno с соавт.…”

“…В аналогичном исследо вании 144 пациентов с хроническими формами ИБС было показано, что при приеме 100 мг КР формы аспирина агре гация тромбоцитов ингибируется аспирином у всех паци ентов. Ни диабет, ни курение, ни воспаление не влияли на эффективность АСК [46]. Исследования этих авторов продемонстрировали, что у пациентов, получающих АСК в КР форме, определяется ацетилирование остатка Ser259 ЦОГ1 в тромбоцитах более чем в 97,5 %.…”

Platelet Carbonic Anhydrase II, a Forgotten Enzyme, May Be Responsible for Aspirin Resistance

“…Aspirin resistance, at molecular level, may be attributed, that is, to changes in efficacy of COX-1 acetylating by ASA [ 6 ]. Studies focusing on the AR phenomenon defined in this way do not precise the time frame between the last aspirin dose and blood sampling [ 6 , 7 ].…”