The Association between Glycosylated Hemoglobin Level and Platelets Reactivity in Patients with Diabetes Mellitus Undergoing Elective Coronary Artery Bypass Grafting.

BACKGROUND: Diabetic patients tend to have increased platelet reactivity after coronary artery bypass grafting (CABG). The aim of this study was to determine the association between hemoglobin A1c (HbA1c) values and platelet reactivity and to evaluate the consequent impact on clinical outcomes in patients undergoing CABG. METHODS: This prospective observational trial consecutively enrolled 225 diabetic patients undergoing CABG, between February 2014 and October 2018. HbA1c levels and platelet function (multiple electrode aggregometry [MEA]) were analyzed the day before surgery and on postoperative day 4 (POD 4). Patients were divided into two groups according to the HbA1c value: HBA1c < 7% and HbA1c ≥ 7%. RESULTS: Significantly higher postoperative ASPI (platelet function test based on arachidonic acid) and ADP (platelet function test based on adenosine diphosphate) test values were observed at POD 4 compared with preoperative values (ASPI test: p < 0.001; ADP test: p < 0.001). The prevalence of preoperative aspirin resistance (AR) was 46.4% relative to 57.2% after surgery showing consistent increase in postoperative AR by approximately 10%. In addition, the prevalence of AR in the HbA1c < 7% group was higher by 10% compared with the HbA1c ≥ 7% group, both before and after surgery. We did not demonstrate differences in clinical outcomes between the HbA1c groups. CONCLUSION: Perioperative assessment of platelet reactivity in diabetic patients detects those with AR who may be at increased risk of adverse ischemic events. A personalized approach guided by MEA and administration of early and more potent antiaggregation therapy after CABG can be beneficial in this group of patients.

Development of a concept for a personalized approach in the perioperative antiplatelet therapy administration/discontinuation management based on multiple electrode aggregometry in patients undergoing coronary artery surgery.

In patients undergoing coronary artery surgery, improvements in clinical outcomes currently rely on continued refinements of the surgical technique and modulation of adjuvant pharmacotherapy. Despite medical and technological advances, negligible rate of bleeding and ischemic events still persist necessitating further improvements in patient management. Platelet function testing (PFT) might play an important role in meticulous balancing between the risk of bleeding and thrombotic events. A suitable balance can be achieved by implementing a personalized, PFT based approach in antiplatelet therapy (APT) administration/discontinuation management. Despite emerging evidence on the widespread variability in platelet inhibitory response to APT, numerous PFT devices and heterogeneity in reporting study results hamper pooling of the evidence which in turn results with a lack of consensus in "on treatment" platelet reactivity associated with ischemic and bleeding events in perioperative phase. The literature on multiple electrode aggregometry (Multiplate(®); Roche Diagnostics, Mannheim, Germany) in coronary artery disease patients was reviewed systematically. Based on the evidence evaluating the relationship between "drug specific" PFT and bleeding or adverse ischemic events, we sought to define therapeutic window for the most commonly administered antiplatelet drugs such as aspirin (ASPI test) and adenosine-diphosphate receptor blockers (ADP test). Preoperatively, APT administration was primarily focused to avoid bleeding complications. ASPI test value of 20 AUC and ADP test value of <73 AUC were set as cut-off values that delineate bleeding tendency. Postoperatively, "therapeutic window" was set to avoid both bleeding and adverse ischemic events. Therapeutic ranges were as follows: 20 AUC < ASPItest ≤ 30 AUC and 19AUC < ADP ≤ 46AUC, respectively. This is the first attempt to define PFT based "therapeutic window" according to, perioperative APT administration/discontinuation management would be targeted. It seems that the "one-size-fits-all" concept of perioperative APT administration management is outdated and further development of PFT based, personalized APT administration/discontinuation management is desirable. This concept therefore presents a possible step forward in patient care and provides a platform for further interventional trials whereby the impact of its application on clinical outcomes would be validated.

Bleeding and Thrombotic Events in Patients Undergoing Mechanical Circulatory Support: A Review of Literature.

Bleeding and thrombotic events are among the most common complications detected in patients with mechanical circulatory support (MCS). Herein, we reviewed the available evidence on the prevalence, etiology, and management of bleeding and thrombotic events in patients following MCS procedures, such as implantation of both intra- and paracorporeal devices that generate either pulsatile or nonpulsatile flow. Extracorporeal life support procedures providing support to the failing heart and lungs were also reviewed. Most bleeding and thromboembolic events occur despite appropriate hemostatic and anticoagulation management based on conventional coagulation laboratory parameters. Prevalence of bleeding events in this population ranges between 5 and 81%. Wide range in prevalence of bleeding reported in literature may be explained by different devices with different anticoagulation protocols being used, as well as different definitions of bleeding outcomes. Although bleeding events are more common than thromboembolic events, the consequences of thrombotic events are often detrimental. Management of bleeding events remains challenging and measures to prevent and treat bleeding events are often followed by thromboembolic events. Therefore, a personalized approach based on point-of-care hemostatic tests and adjusted to device type and patient comorbidities is therefore warranted. To provide advanced understanding of hemostatic disturbances during MCS, prospective trials focused on bleeding and thromboembolic events as primary endpoints should be conducted. Better understanding of the underlying pathophysiology and a shift towards a personalized approach based on functional point-of-care hemostatic properties assessment may provide more favorable clinical outcomes. This should, however, be coupled with further technological improvements providing better device surface hemocompatibility as interaction between blood and device surface affects the hemostatic equilibrium.

Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639).

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.

Definition of acetylsalicylic acid resistance using whole blood impedance aggregometry in patients undergoing coronary artery surgery.

A beneficial effect of acetylsalicylic acid (ASA) on vein graft patency has been described, but some patients experience adverse cardiac events despite appropriate ASA treatment. Study aim was to define ASA resistance using Multiple electrode aggregometry (MEA) preoperatively in group of patients undergoing coronary artery bypass grafting (CABG). Prospective observational trial at University Hospital Center Zagreb enrolled 131 patients scheduled for CABG, and divided them into 4 groups with respect to preoperative antiplatelet therapy (APT). Group 1 received 100 mg ASA per day, Group 2 100 mg ASA + 75 mg clopidogrel per day, Group 3 75 mg clopidogrel per day, and Group 4 did not receive any APT. MEA with ASPI test (sensitive to ASA) and ADP test (sensitive to clopidogrel) was performed prior to surgery. In Group 1, patients were characterized as ASA resistant if their ASPI test value exceeded the 75th percentile distribution. Study enrolled 131 patients. Significant differences both in the ASPI (p < 0.001) and the ADP test (p = 0.038) were observed between patients in different APT groups. In Group (1) ASPI test value of 30 AUC presented 75th percentile of distribution, thus indicating ASA resistance. Group 2 patients had slightly lower ADP test values, but no significant difference occurred (mean 60.05 vs. 63.32 AUC, p = 0.469). In Group 1 and 2, significant correlations between the ADP test and both, platelet count (r = 0.347, p < 0.001) and fibrinogen level (r = 0.364, p < 0.001) were observed. Association between low response to ASA and post-CABG major adverse ischemic events risk increase has been described thus indicating need for ASA resistant patients detection. In patients with preoperative ASPI test exceeding 30 AUC postoperative, ASA dose adjustment or clopidogrel addition according to MEA results should be considered.