Molecular and metabolic characteristics of changes in the platelet sensitivity to antiplatelet therapy in patients with coronary artery disease before and after coronary artery bypass grafting

Abstract

Aim. To study the production of reactive oxygen species (ROS) by platelets in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG), depending on their sensitivity to acetylsalicylic acid (ASA) as a part of ASA monotherapy and dual antiplatelet therapy (DAPT) (ASA+clopidogrel).Material and methods. The study included 104 patients with CAD (ASA monotherapy, 64 patients; DAPT, 40 patients). From day 1 after CABG, they took 100 mg a day of enteric-coated ASA. In the DAPT group, clopidogrel was prescribed for 2-3 days after CABG. All measurements were performed before surgery, on the 1st day and days 8-10 after surgery. Control group consisted of 36 healthy donors. Resistance to ASA was determined at a level of optical platelet aggregation with arachidonic acid >20% at least at one observation point. The spontaneous and ADP-induced chemiluminescence (CL) of platelets with luminol and lucigenin was assessed according to the following parameters: time to maximum intensity (Tmax), maximum intensity (Imax), area (S) under the CL curve, and the ratio of ADP-induced CL S to spontaneous CL S.Results. Throughout the study, 71 patients with CAD were sensitive to ASA (sASA) (ASA monotherapy, 46 patients; DAPT, 25 patients), three patients — resistant (rASA) (ASA monotherapy, 1; DAPT, 2). Sensitivity of other 30 patients (ASA monotherapy, 17; DAPT, 13) changed in different follow-up periods. Compared to the control group, sASA patients had increased values of platelet CL parameters throughout the study, while in the rASA group (ASA monotherapy), Tmax was higher before CABG, and in the rASA group (ASA therapy+clopidogrel), Imax and S were higher on the first day after CABG, while Imax — on days 8-10 after CABG. Compared to sASA, the values of S and Imax before CABG, Imax after CABG, as well as Imax and S on the days 8-10 after CABG in rASA (ASA monotherapy) were significantly lower, while in rASA (ASA therapy+clopidogrel), only the Tmax values were lower on the 8-10 days after CABG.Conclusion. In patients with CAD, depending on the sensitivity to ASA and antiplatelet therapy after CABG, the metabolic activity of platelets in terms of ROS production differs. In sASA patients, ROS synthesis is higher than in healthy individuals, while, in rASA patients (ASA monotherapy), platelets produce ROS levels lower than in sASA. CABG surgery and the addition of clopidogrel to ASA therapy leads to increased ROS production in rASA patients in the postoperative period.

Keywords

• coronary artery disease
• clopidogrel
• acetylsalicylic acid
• resistance
• reactive oxygen species
• platelet