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We suggest that the stable gastric pentadecapeptide BPC 157 may rescue thrombocyte function. We focused on the antithrombotic agent aspirin, clopidogrel, and cilostazol application in rats; arachidonic acid, ADP, collagen, and arachidonic acid/PGE1 platelet aggregation (aggregometry) and blood clot viscoelastic properties (thromboelastometry); and the pentadecapeptide BPC 157. Rats received intragastrically for three days once daily treatment with antithrombotic agents-aspirin (10 mg/kg) or clopidogrel (10 mg/kg) or cilostazol (10 mg/kg). Medication (BPC 157 (10  μ g/kg) or an equal volume of saline (5 ml/kg)) was given intragastrically, immediately after each antithrombotic agent application. For multiple electrode aggregometry and modified rotational thromboelastometry studies, blood sampling was at 2 h after last application. Adenosine diphosphate (ADP test 6.5  μ M), arachidonic acid (ASPI test 0.5 mM), a combination of arachidonic acid and prostaglandin E1 (ASPI test 0.5 mM and PGE1-test 30 nM), and collagen (COL test 3.2  μ g/ml) were used as aggregation agonists. Given with aspirin, clopidogrel, or cilostazol in rats, BPC 157 counteracted their inhibitory effects on aggregation activated by arachidonic acid, ADP, collagen, and arachidonic acid/PGE1. Specifically, this includes recovery of the aggregation induced by arachidonic acid ( vs. aspirin, vs. clopidogrel, and vs. cilostazol), arachidonic acid/PGE1 ( vs. cilostazol), ADP ( vs. clopidogrel), or collagen ( vs. clopidogrel). Contrarily, there is no effect on the used tests (extrinsic/intrinsic hemostasis system, the fibrin part of the clot) EXTEM, INTEM, and FIBTEM; clotting time; clot formation time; alpha-angle; maximum clot firmness; lysis index after 30 minutes; and maximum lysis. In conclusion, we revealed that BPC 157 largely rescues thrombocyte function., Competing Interests: All authors declare that they have no conflict of interest., (Copyright © 2019 Sanja Konosic et al.)

Background: Atrial fibrillation (AF) contributes to a prothrombotic state through platelet activation. It is unclear whether increased platelet aggregability in patients with AF is caused by the underlying cardiovascular condition rather than the arrhythmia per se. We investigated the effect of postoperative atrial fibrillation (POAF) on platelet reactivity after coronary artery bypass grafting (CABG)., Methods: This study is a post hoc analysis from a randomized controlled trial (ClinicalTrials.gov: NCT01159639) based on patients undergoing elective primary CABG. Patients were dichotomized according to POAF. Postoperative platelet function testing with arachidonic acid as the platelet agonist (ASPI test) was used to define high on-aspirin platelet reactivity (HAPR). ΔASPI presented the difference between pre- and postoperative ASPI test values. To account for the isolated effect of POAF on platelet reactivity, a propensity score analysis was applied., Results: Overall incidence of POAF was 23% (92 of 398 patients). HAPR was detected in 54% (214 of 398) of patients. HAPR was more prevalent among patients with POAF when compared with patients without POAF (64.1% versus 50.7%; odds ratio [OR], 1.74; 95% confidence interval [CI], 1.08-2.82; p = 0.023). The propensity score model produced a subcohort of patients that was well balanced for comorbidities. When compared with the matched group without POAF, the POAF group maintained its prevalence for HAPR (64.1% versus 45.7%; OR, 2.13; 95% CI, 1.18-3.85; p = 0.012) and had greater ΔASPI values (15.0 [IQR, 0.0-36.0] vs 8.0 [IQR, -5.5-19.5]; p = 0.030)., Conclusions: The main finding of our study indicates there is added platelet activation in patients with POAF after CABG before and after controlling for pathologic conditions through propensity matching. The present study does not prove a causal association between POAF and HAPR., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Individual variability in the response to aspirin, has been established by various platelet function assays, however, the clinical relevance of aspirin resistance (AR) in patients undergoing coronary artery bypass grafting (CABG) has to be evaluated. Our working group conducted a randomized controlled trial (NCT01159639) with the aim to assess impact of dual antiplatelet therapy (APT) on outcomes among patients with AR following CABG. Patients that were aspirin resistant on fourth postoperative day (POD 4) were randomly assigned to receive either dual APT with clopidogrel (75 mg) plus aspirin (300 mg)-intervention arm or monotherapy with aspirin (300 mg)-control arm. This exploratory analysis compares clinical outcomes between aspirin resistant patients allocated to control arm and patients that have had adequate platelet inhibitory response to aspirin at POD 4. Both groups were treated with 300 mg of aspirin per day following surgery. We sought to evaluate the impact of early postoperative AR on outcomes among patients following CABG. Exploratory analysis included a total number of 325 patients. Of those, 215 patients with adequate response to aspirin and 110 patients with AR allocated to aspirin monotherapy following randomization protocol. The primary efficacy end point (MACCEs-major adverse cardiac and cardiovascular events) occurred in 10 and 6 % of patients with AR and with adequate aspirin response, respectively (p = 0.27). Non-significant differences were observed in bleeding events occurrence. Subgroup analysis of the primary end point revealed that aspirin resistant patients with BMI > 30 kg/m(2) tend to have a higher occurrence of MACCEs 18 versus 5 % (relative risk 0.44 [95 % CI 0.16-1.16]; p = 0.05). This exploratory analysis did not reveal significant impact of aspirin resistance on outcomes among patients undergoing CABG. Further, sufficiently powered studies are needed in order to evaluate clinical relevance of AR in patients undergoing CABG.

Coronary artery bypass grafting is pivotal in the contemporary management of complex coronary artery disease. Interpatient variability to antiplatelet agents, however, harbors the potential to compromise the revascularization benefit by increasing the incidence of adverse events. This study was designed to define the impact of dual antiplatelet therapy (dAPT) on clinical outcomes among aspirin-resistant patients who underwent coronary artery surgery. We randomly assigned 219 aspirin-resistant patients according to multiple electrode aggregometry to receive clopidogrel (75 mg) plus aspirin (300 mg) or aspirin-monotherapy (300 mg). The primary end point was a composite outcome of all-cause death, nonfatal myocardial infarction, stroke, or cardiovascular hospitalization assessed at 6 months postoperatively. The primary end point occurred in 6% of patients assigned to dAPT and 10% of patients randomized to aspirin-monotherapy (relative risk 0.61, 95% confidence interval 0.25 to 1.51, p = 0.33). No significant treatment effect was noted in the occurrence of the safety end point. The total incidence of bleeding events was 25% and 19% in the dAPT and aspirin-monotherapy groups, respectively (relative risk 1.34, 95% confidence interval 0.80 to 2.23, p = 0.33). In the subgroup analysis, dAPT led to lower rates of adverse events in patients with a body mass index >30 kg/m(2) (0% vs 18%, p <0.01) and those <65 years (0% vs 10%, p = 0.02). In conclusion, the addition of clopidogrel in patients found to be aspirin resistant after coronary artery bypass grafting did not reduce the incidence of adverse events, nor did it increase the number of recorded bleeding events. dAPT did, however, lower the incidence of the primary end point in obese patients and those <65 years., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Residual platelet reactivity (RPR) following coronary artery bypass grafting (CABG) might be related to thrombotic complications and major ischemic cardiac events. The aim of this study was to evaluate the changes in platelet reactivity monitored pre- and postoperatively using multiple-electrode aggregometry (MEA) and to propose an alternative therapeutic approach in a subgroup of patients with postoperative RPR. Ninety-nine patients undergoing elective CABG were enrolled in the study, of whom 41 (41.4%) were diabetic. Preoperatively, all patients received 100 mg acetylsalicylic acid (ASA), with 47 of 99 (47.4%) patients receiving an additional 75 mg clopidogrel (CLO). The blood samples were drawn the day before surgery, and on the first and 4th postoperative day. Platelet count and fibrinogen level were documented, as well as type and daily dose of antiplatelet therapy (APT) received pre- and postoperatively. Multiple-electrode aggregometry using tests based on arachidonic acid (ASPI test) and adenosine diphosphate (ADP test) was performed on the day before and 4 days after surgery. Preoperatively, we detected 31 of 99 (31.3%) patients with RPR (ASPI > 30 AUC). Platelet count correlated with both the ASPI (P = 0.03) and ADP (0.002) tests. Fibrinogen correlated with ADP test values (P < 0.001) and was found to have a higher level in the diabetic subgroup (P = 0.01). In comparison with preoperative results, we detected higher values of ASPI test postoperatively (P = 0.04), with 46 of 99 (46.5%) patients having RPR despite a higher dose of 300 mg ASA being administered. Postoperatively, diabetic patients had higher ASPI test values (P = 0.01), and a higher proportion of patients with RPR compared with the nondiabetic subgroup (58.5 vs 38%, P = 0.04). The subgroup of patients with detected ASPI >30 AUC at the 4th postoperative day consequently received as a part of our clinical routine an additional 75 mg CLO per day, in terms of platelet inhibition optimization. Multiple-electrode aggregometry can recognize patients with RPR during both the pre- and post-CABG period. Postoperatively administered ASA (300 mg) did not sufficiently inhibit platelet aggregation in 46.5% of post-CABG patients. In this group of patients a switch to dual APT should be considered.

Background: Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events., Methods: Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded., Discussion: This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).

The article presents a clinical research review of the diagnosis and impact of antiplatelet therapy resistance in patients who undergo surgical myocardial revascularization. It searches PUBMED and MEDLINE databases through predefined search criteria. It discusses novel antiplatelet agents including Prasugrel, Ticagrelor, and Cangrelor.

The authors comment on the update from the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) on dual antiplatelet therapy in patients with coronary heart disease. They discuss changes to the use of acetylsalicylic acid, clopidogrel, prasugrel and ticagrelor and the association of adenodiphosphate-dependent platelet aggregation preoperatively with the risk for perioperative bleeding complications in coronary artery bypass grafting patients.

A letter to the editor is presented in response to the article "Antiplatelet therapy at the time of coronary artery bypass grafting: a multicentre cohort study" by Kremke et al. in the 2013 issue.

The article discusses the higher risk of Red Blood Cell (RBC) transfusion in isolated coronary artery bypass grafting (CABG) as predicted by the study of De Santo LS and colleagues published in the Journal of Thrombosis and Thrombolysis. The topics discussed include eight predictive factors of the risk obtained by regression logistic analysis, objective quantification of platelet activity and assessment of viscoelastic blood clot properties.