Frantisek Bednar

Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery: Results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes (CABARET)

OBJECTIVES Changes in hemostasis after off-pump coronary artery bypass grafting are still being discussed. There is a lack of information about platelet activity and aspirin efficacy after coronary artery bypass grafting. The aim of this study was to assess and compare platelet activity and aspirin efficacy early and late after off-pump and on-pump coronary artery bypass grafting. METHODS Eighty patients were enrolled in a prospective randomized study. Platelet activity was determined based on membrane expression of antigen CD62P (P-selectin) by means of flow cytometric analysis. Aspirin efficacy was assessed by using arachidonic acid-induced platelet aggregation. Blood samples were collected before the operation, immediately postoperatively, and on days 1, 2, 5, and 30. RESULTS In the off-pump group expression of P-selectin was markedly increased in comparison with preoperative values, with a maximum difference observed on day 2 (+53%, P = .02), and it was significantly higher compared with that seen in the on-pump group on days 2 and 5 (+53% vs +4%, P = .004, and +20% vs -16%, P = .005). On day 30, P-selectin expression was similar both between the groups and in comparison with the preoperative values. Arachidonic acid-induced platelet aggregation was gradually decreasing until day 30, but on day 2, there was an unexpected increase in aggregation that was more expressed in the off-pump group. CONCLUSIONS The platelet activity is higher in the early postoperative period in off-pump compared with on-pump coronary artery bypass grafting. The present aspirin strategy seems to be insufficient in the early postoperative period, irrespective of the surgical technique used.

Evaluation of aspirin's effect on platelet function early after coronary artery bypass grafting.

OBJECTIVE Aspirin therapy decreases mortality and ischemic complication rates after coronary artery bypass grafting (CABG). However, platelet inhibition after oral aspirin seems to be insufficient in the early postoperative period. There are incomplete data reporting aspirin efficacy early after CABG. The aim of this study was to assess the pharmacologic effect of aspirin on platelets in the first postoperative days using the most specific laboratory tests for the evaluation of aspirin efficacy. DESIGN A prospective study. SETTING A clinical study in one cardiac surgery center and measurements in two pharmacologic institutions. PARTICIPANTS Thirty patients. INTERVENTIONS Postoperative aspirin efficacy (200 mg/d) was assessed by the suppression of serum thromboxane B(2) (TxB(2)) and by arachidonic acid-induced aggregometry using the MULTIPLATE analyzer. Samples were collected before surgery and on postoperative days 1-5. METHODS AND MAIN RESULTS The median baseline value (range) of serum TxB(2) was 1.6 ng/mL (1.4-1.9). The median TxB(2) inhibition >90% (the value required for full platelet inhibition) was not achieved until day 5 (-91%, 0.13 ng/mL [0.08-0.22], p < 0.001) and in only 55% of patients. The median baseline ASPI value was 805 (640-975) aggregation units (AU)*min. A significant decrease in aspirin insufficiency was not seen before postoperative day 5 (390 [243-621], p < 0.003) and only 34% of patients reached an effective platelet inhibition on day 5 (cutoff < 300 AU*min). CONCLUSIONS The effect of aspirin on inhibition of TxB(2) production and arachidonic acid-induced platelet aggregation is impaired during the first postoperative days after CABG. A more effective antiplatelet strategy presumably could increase early graft patency and improve clinical outcomes after CABG.

Glycemia, triglycerides and disease severity are best associated with higher platelet activity in patients with stable coronary artery disease

BackgroundInconsistent findings are reported about the relation of platelet activity to disease severity in stable patients with chronic coronary artery disease (CAD). Nevertheless, most reports studied only very small groups of patients. The purpose aim of our study was to assess the relation of platelet activity to disease severity in sufficient number of patients with chronic CAD.MethodsOne hundred and sixty stable patients with chronic CAD were studied (25 with single-, 63 with double- and 72 with triple-vessel disease). 91% of them were on aspirin, 1.6% on clopidogrel medication. Platelet activity was determined as membrane expression of antigens CD62P (P-selectin, as % of positive cells) and CD41 (part of GpIIb/IIIa integrin, as mean fluorescence intensity) by flow cytometry. Platelet aggregability was measured by ADP-optical aggregometry. Data sets were compared by Kruskal-Wallis test, correlation by Spearman test. Data are shown as median with 25–75 percentiles.ResultsMembrane CD62P expression correlated with vessel severity (P < 0.001, Kruskal-Wallis test). Patients with triple-vessel disease had the highest CD62P expression (1.6; 1.1–2.0) followed by patients with double-vessel (1.2; 0.63–1.95) and single-vessel (0.7; 0.30–0.84) disease. Positive correlation was found between CD62P expression with triglycerides (r = 0.49, P < 0.05) and CD41 with fasting glucose (r = 0.48, P < 0.05). No differences in CD41 expression or ADP aggregability were found between groups.ConclusionHigher platelet activity is present in patients with more severe CAD. More aggressive anti-platelet treatment in these patients should be considered, especially when metabolic syndrome is simultaneously present.

Selection of P2Y12 antagonist, treatment initiation, and predictors of high on-treatment platelet reactivity in a "Real World" registry

OBJECTIVE The present study aimed to compare characteristics related to selection of a P2Y₁₂ antagonist, investigate initiation of therapy with new-generation drugs, and identify predictors of high on-treatment platelet reactivity (HTPR) in patients with acute coronary syndrome treated with stent percutaneous coronary intervention (PCI). METHODS AND RESULTS Data from 589 patients in the LAPCOR (Laboratory AntiPlatelet efficacy and Clinical Outcome Registry; ClinicalTrials.gov Identifier: NCT02264912) registry was analyzed. P2Y₁₂ receptor antagonist efficacy was measured by VASP phosphorylation 24 ± 4 hours after a loading dose of clopidogrel (600 mg, N=407), prasugrel (60 mg, N=106), or ticagrelor (180 mg, N=76) and expressed by platelet reactivity index (PRI). HTPR was defined as PRI ≥50%. Patients treated with prasugrel were significantly younger and had significantly higher hemoglobin levels than those who received clopidogrel or ticagrelor, while chronic kidney disease was significantly more prevalent in the ticagrelor group. Almost all invasively managed patients given new-generation drugs received a loading dose after coronary angiography. Mean residual PRI and HTPR were significantly higher after clopidogrel (44.2 ± 23.1% and 42.2%, respectively) vs. prasugrel (17.7 ± 18.0% and 9.4%, respectively) or ticagrelor (18.8 ± 17.0% and 7.9%, respectively; all p<0.001). Among multiple variables tested, HTPR in patients treated with the new agents significantly related only to platelet count (p=0.014) and mean platelet volume (p=0.03). CONCLUSION Safety is the most important aspect under consideration in choosing new agents for an individual patient. Other than platelet count and mean platelet volume, factors known as predictors of higher platelet reactivity, did not influence the efficacy of new-generation P2Y₁₂ receptor antagonists.

Pharmacodynamic Effect of Clopidogrel in Patients Undergoing Transcatheter Aortic Valve Implantation

The aim of this study was to analyze periprocedural and mid-term effect of clopidogrel on platelet function using the VerifyNow P2Y12 point-of-care assay in patients undergoing TAVI. Platelet reactivity was measured at the beginning of the procedure after 300 mg clopidogrel bolus administration and during the follow-up (at 1 month after the procedure) in 52 patients undergoing TAVI using the Medtronic CoreValve prosthesis (Medtronic CoreValve). A cutoff value of 240 PRU was used to identify nonresponders to clopidogrel treatment with high residual platelet reactivity (HRPR). Baseline HRPR was identified in 80% of patients and in 72% of patients during 6-month follow-up. There was no significant difference in the pharmacodynamic effects of clopidogrel on platelet reactivity from baseline to 6-months follow-up (297 ± 57 vs. 275 ± 62; P = 0.058). Ischemic event occurred only in 3 patients (5.8%) from the study group. In conclusion, majority of patients undergoing TAVI had high residual platelet reactivity after pretreatment with 300 mg of clopidogrel and during the 6-month follow-up at dual antiplatelet treatment. The noneffectiveness of clopidogrel in the TAVI population raises the question of the routine use of dual antiplatelet treatment in this setting.

Invasive Hemodynamic Assessment of Cardiac Output State after MitraClip Therapy in Nonanaesthetized Patients with Functional Mitral Regurgitation

Background. Surgical correction of mitral regurgitation (MR) can lead to postoperative low cardiac output state. We aimed to assess the acute hemodynamic changes after percutaneous MitraClip therapy (a unique model without influence of factors linked to surgical procedure) in patients with functional MR without the influence of general anaesthesia. Methods. We studied invasive hemodynamic parameters in 23 patients before procedure (conscious, nonsedated patients), during procedure (intubated patients), and the first day after MitraClip implantation (conscious, extubated patients). Results. Mitral valve clipping significantly increased cardiac index (CI) (from 2.0 ± 0.5 to 3.3 ± 0.6 L/min/m2; p < 0.01). Conversely, there was significant reduction in the mean pulmonary capillary wedge pressure (PCWP) (from 18.6 ± 5.7 to 10.5 ± 3.8 mmHg; p < 0.01), mean pulmonary artery pressure (from 29.8 ± 10.9 to 25.2 ± 10.3 mmHg; p = 0.03), and pulmonary vascular resistance index (from 531 ± 359 to 365 ± 193 dyn·s·cm−5/m2; p = 0.03). Conclusions. The functional MR therapy with percutaneous MitraClip device results in significant increase in CI (+66%) and concomitant decrease in PCWP (−42%). None of our patients developed low cardiac output state. Our results support the idea that significant part of low cardiac output state after cardiac surgery is due to surgery related factors rather than due to increase in afterload after MR elimination.

Higher platelet activity is present in patients with restenosis after percutaneous coronary intervention compared with patients with an occlusion of coronary artery bypass graft

The aim of the study was to compare platelet activity between patients with an occlusion of bypass graft after coronary artery bypass graft surgery and restenosis after percutaneous coronary intervention (PCI); that is, between patients with reappearance of ischemia after two different kinds of coronary revascularization. Thirty patients were studied in a cross-sectional designed study. Fifteen of them were patients with the worst bypass graft patency from Prague-4 study (control protocol-driven coronary angiography performed at 1 year after surgery; originally 47 bypass grafts implanted, 94% of venous grafts occluded). The remaining 15 were patients with restenosis 3–12 months after PCI. Blood samples were drawn at least 12 weeks after coronary angiography. Platelet activity was determined by membrane expression of P-selectin (CD62P, % of positive cells) by flow cytometry, aggregability by ADP aggregometry. Data are expressed as mean ± SEM. Both groups were similar with respect to age, BMI and presence of diabetes mellitus. No patient suffered from acute coronary syndrome. P-selectin expression was significantly higher in the patients with restenosis compared with patients with bypass graft occlusion (1.96 ± 0.07 vs. 0.77 ± 0.03, P < 0.001, Wilcoxon test). ADP aggregometry was not different between groups (55.5 ± 1.1 vs. 56.1 ± 0.8, P = NS). Higher platelet activity is present in the patients with restenosis after PCI compared with the patients with the occlusion of bypass graft. Platelet activity play more important role in the development of restenosis after PCI compared with the occlusion of bypass graft after coronary artery bypass graft surgery, at least in the period up to 1 year after revascularization.