Reaction Units Research Articles

Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow Assay.

Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients who had percutaneous coronary intervention within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event. Secondary outcomes included VerifyNow platelet reactivity units (PRUs) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42%-45%), followed by NPO status (26%-28%) and MCS alone (22%-24%). The primary outcome of major adverse cardiovascular event occurred in 1 patient (1.1%). Of 92 patients, 77% had a P2Y12 level collected within 24 hours, and 89% of the cohort was able to achieve the goal P2Y12 PRU of <194. The median P2Y12 value within 24 hours of cangrelor initation was 115 PRU (40-168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients who received a drug-eluting stent in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

Early detection of resistance to dual antiplatelet therapy in patients who have undergone percutaneous coronary intervention using the VerifyNow test and associated factors.

Resistance to dual antiplatelet therapy (DAPT), including aspirin and clopidogrel, in patients who have undergone percutaneous coronary intervention (PCI) leads to the inability to prevent thrombotic complications. The present study aimed to evaluate early resistance to aspirin and clopidogrel in patients following PCI using the VerifyNow test and associated factors. A total of 50 patients diagnosed with acute coronary syndromes (ACS) who underwent emergency PCI and received DAPT were recruited in the present study. The detection of resistance to aspirin and clopidogrel was performed using the VerifyNow system. Resistance to aspirin was determined with VerifyNow Aspirin >550 aspirin reaction units (ARU). Resistance to clopidogrel was determined with VerifyNow P2Y12 >208 P2Y12 reaction units (PRU). The resistance rate to aspirin was 14%, while the resistance rate to clopidogrel was higher, at 34%. There were 2 patients with resistance to aspirin and clopidogrel (4%). Univariable logistic regression analysis revealed that diabetes, the use of β-blockers, and low levels of hemoglobin and hematocrit were associated with resistance to clopidogrel. Following multivariable logistic regression analysis, only the use of β-blockers was truly associated with resistance to clopidogrel. On the whole, the results of the present study may also prove to be helpful in the selection of therapeutic drugs for patients undergoing PCI and who are diagnosed with ACS.

Abstract WP150: Correlation Between CYP2C19 Genotype and Platelet Reactivity Units in Patients Receiving Clopidogrel After Acute Ischemic Stroke

Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard of care for secondary prevention in non-cardioembolic minor acute ischemic stroke (AIS) and high-risk transient ischemic attack (TIA). However, clopidogrel is a prodrug metabolized to its active form by the CYP2C19 enzyme and therefore has decreased efficacy in patients with at least one loss-of-function (LOF) allele in the CYP2C19 gene that encodes the enzyme. The use of ticagrelor over clopidogrel for DAPT improves outcomes in CYP2C19 LOF carriers; however, CYP2C19 genotyping is not currently standard practice in the cerebrovascular population. P2Y12 assays that measure P2Y12 receptor-mediated platelet aggregation in platelet reactivity units (PRUs) are more widely accessible, but it is unclear if this assay correlates with CYP2C19 genotype in this population. Therefore, we aimed to investigate the correlation between CYP2C19 genotype and PRUs to evaluate PRUs as a potential surrogate biomarker for identifying suboptimal clopidogrel response. We hypothesized that PRUs would be increased in CYP2C19 LOF carriers compared to non-carriers due to the reduced bioactivation of clopidogrel in patients with decreased CYP2C19 enzymatic function. This prospective, observational study enrolled patients &gt; 18 years of age presenting with minor AIS or high-risk TIA and discharged from University of Virginia Health on DAPT for secondary stroke prevention. A whole blood sample for P2Y12 assay and CYP2C19 genotyping was obtained at least 12 hours after a 300 milligram clopidogrel loading dose. The primary outcome was the correlation between PRUs and CYP2C19 LOF allele carrier status. Of 35 patients genotyped, 27 (77%) subjects self-reported European ancestry, 7 (20%) African ancestry, and 1 (3%) Asian ancestry. Six participants (17%) were found to be LOF carriers. LOF carriers had significantly increased PRUs compared to non-carriers (mean difference +103.7; 95% CI +30.71 to +176.1; p&lt;0.01), indicating diminished pharmacodynamic response to clopidogrel. This suggests that measurement of PRUs via an accessible and established P2Y12 assay may be a viable surrogate biomarker for identifying suboptimal clopidogrel response in the cerebrovascular population.

Platelet reactivity and activated clotting time predict hemorrhagic site complications in patients with chronic coronary syndromes undergoing percutaneous coronary interventions.

Radial access is preferred in patients with chronic coronary syndromes (CCSs) treated with ad hoc percutaneous coronary intervention (PCI). Antithrombotic and antiplatelet treatment before PCI may affect outcomes at vascular access sites. QuikClot Radial is a kaolin-based band that may shorten hemostasis time. Using point-of-care testing, we investigated the effect of antithrombotic and antiplatelet treatment on access-site complications. This prospective observational study included consecutive patients with CCS on chronic aspirin therapy referred for ad hoc PCI. The activated clotting time (ACT), global thrombosis test and VerifyNow P2Y 12 test were done sequentially after unfractionated heparin (UFH) and clopidogrel administration. Patients were monitored for radial artery patency, bleeding and local hematoma until discharge. We enrolled 40 patients [mean age, 68.8 ± 8.8 years; men, 30 (75%)] who received UFH (median dose, 8000 IU; interquartile range, 7000-9000 IU) and clopidogrel (600 mg). All radial arteries remained patent during follow-up. Local bleeding and hematomas were noted in 11 patients (27.5%) each. Patients with bleeding had lower mean platelet activity at 2 h [122.5 ± 51 platelet reactivity units (PRU) vs. 158.7 ± 43 PRU, P = 0.04] and higher ACT (216.9 ± 40 s vs. 184.6 ± 28 s, P = 0.006) than patients without bleeding. An ACT >196 s at 2 h predicted bleeding or hematoma (AUC, 0.72; 95% CI, 0.56-0.85, P = 0.008). Lower platelet activity and higher ACT after PCI were associated with higher bleeding risk at a vascular access site. Point-of-care testing of ACT after the procedure may help identify patients with CCS undergoing PCI who are at higher risk of access-site bleeding.

Assessing the efficacy of VerifyNow platelet-function testing in predicting postoperative hemorrhagic complications of neuroendovascular surgery: A systematic review and meta-analysis (part 2).

Dual antiplatelet therapy is used to reduce the risk of thromboembolic complications in neuroendovascular surgery. However, the predictive utility of preoperative platelet-sensitivity testing for decreasing bleed risk in patients undergoing endovascular neurointervention remains unclear. We conducted a systematic review and meta-analysis to illustrate the association between platelet response and risk of hemorrhagic complications from neuroendovascular surgery, examine the efficacy of the VerifyNow platelet reactivity unit (PRU) assay in predicting hemorrhagic outcomes, and assess whether a clinically useful threshold for platelet response can be defined to standardize guidelines. PubMed, Embase, and Scopus were searched. Articles were screened for relevance by title and abstract, followed by full text. Of 735 resultant articles, 17 studies of 2084 patients undergoing neuroendovascular intervention were included. Diagnoses included both intracranial and extracranial pathologies, of which 37.8% were treated with flow diversion, 22.4% with stent-assisted coil embolization, 14.3% with intracranial stenting, 12.8% with simple coil embolization, 5.8% with balloon-assisted coil embolization, 2.0% with extracranial stenting, and 4.8% with an alternate method. Precisely, 52.9% (9 out of 17) of studies determined platelet hyperresponse to be an independent predictor of postoperative hemorrhagic complications, with 11.8% (2 out of 17) of studies reporting a similar but non-statistically significant trend. 35.3% (6 out of 17) of studies found no relationship between platelet response and postoperative hemorrhagic complications. The estimated clinical threshold for PRU to prevent hemorrhagic complications varied considerably across studies (range: <46-118 PRU). Meta-analysis found platelet hyperresponse to have more than a 3-fold increased risk of hemorrhagic complications compared to normoresponders (relative risk = 3.2, p = 0.001). Although this meta-analysis shows the predictive utility of the P2Y12 assay for postoperative hemorrhagic complications in neuroendovascular surgery, the optimal therapeutic threshold for minimizing bleeding risk is still uncertain. To better understand the utility of the P2Y12 assay in the perioperative period, further prospective research is needed.

Assessing the efficacy of VerifyNow platelet-function testing in predicting postoperative thromboembolic complications of neuroendovascular surgery: A systematic review and meta-analysis (part 1).

Despite the heavily debated use of routine platelet-function testing, the VerifyNow Platelet Reactivity Unit (PRU) assay has been increasingly adopted as standard of care for assessing risk of postoperative thromboembolic complications of neuroendovascular surgery. We conducted a systematic review and meta-analysis to examine the relationship between platelet response and risk of ischemic events from neuroendovascular surgery, assess the efficacy of point-of-care platelet-function testing in predicting thromboembolic outcomes, and assess whether a clinically useful threshold for platelet response can be defined in order to standardize guidelines. PubMed, Embase, and Scopus were searched. Following deduplication, articles were first screened for relevance by title and abstract, followed by full text. Of 735 resultant articles, 22 studies consisting of 3266 patients undergoing neuroendovascular intervention were included. Diagnoses included both intracranial and extracranial pathologies, of which 45.8% were treated with flow diversion, 16.4% with stent-assisted coil embolization, 15.8% with intracranial stenting, 12.0% with simple coil embolization, 3.4% with balloon-assisted coil embolization, 3.6% with extracranial stenting, and 3.0% with an alternate method. 54.5% (12/22) of studies determined platelet hyporesponse to be an independent predictor of postoperative thromboembolic complications, with 27.3% (6/22) of studies reporting a similar, but non-statistically significant trend. 18.2% (4/22) of studies found no relationship between platelet response and postoperative thromboembolic complications. The estimated clinical threshold for PRU to prevent thromboembolic complications varied greatly across studies (Range: > 144-295 PRU). Meta-analysis found platelet hyporesponse to have a 2.23-fold increased risk of thromboembolic complications compared to normoresponders (RR = 2.23, P = 0.03). While PRU demonstrates a significant predictive value for postoperative thromboembolic complications of neuroendovascular surgery, the target therapeutic threshold for minimizing ischemic events remains unclear. Further studies, such as large multicenter cohorts of the existing data, are needed to standardize guidelines.

High platelet reactivity strongly predicts early stent thrombosis in patients with drug-eluting stent implantation

Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p < 0.001). In multivariable analysis, PRU ≥ 252 (OR, 5.10; 95% CI 1.58–16.46; p = 0.006) and aspirin reaction unit ≥ 414 (OR 4.85; 95% CI 1.07–21.97; p = 0.040) were independent predictors of EST. The cumulative incidence of primary composite outcome at one year was significantly higher in the EST group (38.2% vs. 3.9%, Log-rank p < 0.001). In patients treated with clopidogrel after successful DES implantation, EST was associated with higher platelet reactivities, and a greater risk of cardiovascular events.Trial Registration: clinicaltrials.gov Identifier: NCT04734028.

Platelet Function Testing to Guide Cangrelor Dosing in Patients with Temporary Mechanical Circulatory Support or as a Bridge to Procedure.

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12-24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85-208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375-0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis.

Analysis of Platelet Function Testing in Children Receiving Aspirin for Antiplatelet Effects.

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children.

Prognostic Implication of Platelet Reactivity According to Procedural Complexity After PCI: Subanalysis of PTRG-DES Consortium

BackgroundComplex percutaneous coronary intervention (C-PCI) and high platelet reactivity (HPR) have been proposed as representative risk factors for the high ischemic phenotype. Uncertainty remains regarding the relative prognostic importance of these factors. ObjectivesThis study aimed to investigate the prognostic implication of HPR according to procedural complexity. MethodsPatients treated with drug-eluting stent implantation (PTRG-PFT cohort; N = 11,714) were classified according to procedural complexity. HPR criteria were determined using VerifyNow (≥252 P2Y12 reaction units). The major adverse cardiac and cerebrovascular events (MACCE) (the composite of all-cause death, myocardial infarction, definite stent thrombosis, or stroke) and major bleeding were assessed for up to 3 years. ResultsC-PCI was performed in 3,152 patients (26.9%). C-PCI significantly increased the risk of MACCE (HRadjusted: 1.21; 95% CI: 1.01-1.44; P = 0.035), driven by a higher rate of all-cause death (HRadjusted: 1.45; 95% CI: 1.15-1.83; P = 0.002), although it did not increase the risk of major bleeding. Irrespective of procedural complexity, the HPR phenotype was significantly associated with MACCE (Pinteraction = 0.731) and all-cause mortality (Pinteraction = 0.978), in which the prognostic implication appeared prominent within 1 year. The HPR phenotype did not show a significant interaction with any type of C-PCI. In addition, the number of complexity features per procedure did not proportionally increase the risk of MACCE. ConclusionsC-PCI was significantly associated with 3-year risk of MACCE and all-cause death. The HPR phenotype appears to have a similar prognostic implication irrespective of the type and extent of procedural complexity. (Platelet Function and Genotype-Related Long-Term Prognosis in DES-Treated Patients [PTRG-DES]; NCT04734028)

Periprocedural antiplatelet medication assessed by VerifyNow for neuroendovascular treatment: Comparison of prasugrel with clopidogrel

Objective The maintenance dose of prasugrel (PRAS) for neuroendovascular treatment requires much research. We report the antiplatelet effect of PRAS measured by VerifyNow P2Y12 reaction units (PRUs) in patients during the perioperative period of neuroendovascular treatment. Methods Between January 2017 and January 2023, 230 patients who underwent endovascular treatment for unruptured intracranial aneurysms or carotid artery stenosis at our institution were retrospectively identified. Patients received dual antiplatelet therapy with 100 mg aspirin (ASA) and 75 mg clopidogrel (CLP)/day (CLP group, n = 186) or 100 mg ASA and 3.75 mg PRAS/day (PRAS group, n = 44) 2 weeks before the procedures. The PRU value was compared between the CLP and PRAS groups. In the study, we defined 95≦PRU &lt; 208 as the optimal range. Perioperative complications within seven days of surgery were also analyzed. Results The mean value of PRU was significantly low in the PRAS group (179.13 ± 66.03 in CLP vs. 154.75 ± 54.01 in PRAS, p = 0.024). The proportion of the patients who exhibited 95≦PRU &lt; 208 was significantly higher in the PRAS group (55.4% vs. 72.7%, p = 0.036). Ischemic and hemorrhagic complication rates were not significantly different between the CLP and PRAS groups (7.6% vs. 0%, p = 0.076; 4.7% vs. 0%, p = 0.361). The ischemic complication rate was higher in patients with a PRU &gt; 208 than in those with PRU &lt; 208 (12.5% vs. 3.8%, p = 0.044). The hemorrhagic complication rate was not significantly different between the PRU &lt; 95 and 95≦PRU groups (8.4% vs. 3.2%, p = 0.224). Conclusions Maintenance dose PRAS further decreased the PRU value and reached the optimal range in more cases than CLP during the perioperative period of neuroendovascular treatment. Ischemic complications significantly increased in the 208 &lt; PRU group.

Study on the effect of cyclic catalytic pyrolysis on sludge pyrolysis products

Pyrolysis technology has become a hot issue in the industry of harmless treatment of sludge in recent years. The present ex-situ catalysis process suffers from the defects of unidirectional flow of pyrolysis steam, easy to form coke buildup on the catalyst surface, and poor heating value of the output heavy tar, which is difficult to be reutilized. This paper designed a cyclic catalytic cracking by pyrolytic steam process to optimize the above defects: under the optimal experimental conditions (pyrolysis starting temperature was 500 ℃, final temperature was 800 ℃, iron-based carbon catalyst dosage was 4 g, and motor speed was 1050 r/min), this process generated more pyrolysis gas and light tar. The increase in pyrolysis temperature had the most significant effect on pyrolysis gas yield, the dosage of iron-based carbon catalyst had the most significant effect on pyrolysis gas composition, and the increase in motor speed had the most significant effect on tar cracking. The cyclic catalytic cracking by the pyrolytic steam process can increase the residence time of pyrolysis steam in the reaction unit and promote the secondary cracking, catalytic, and reforming effects of tar.

Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response.

Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2.

Photothermal hydrogel-integrated paper-based point-of-care platform for visible distance-readout of glucose

BackgroundThe accurate detection of glucose and cholesterol plays a pivotal role in disease diagnosis and home care. To this end, biochemical analyzers have become extensively utilized tools for measuring disease biomarkers. Nonetheless, their poor portability and high cost have restricted their accessibility, limiting their use to laboratory settings and hindering the adoption of point-of-care testing (POCT). In contrast, the emergence of portable and affordable paper-based testing platform has revolutionized diagnostic testing by providing distance signals, enhancing intuitiveness and visual accessibility. Consequently, these platforms have become increasingly suitable for POCT. ResultsWe have developed a POCT platform that integrated AuNS@Ag, stimulus-responsive hydrogel and test strips, enabling visual distance reading of glucose. The silver-coated AuNS and enzyme were encapsulated within a temperature-responsive N-isopropylacrylamide-acrylamide (NIPAM-AcAm) hydrogel to act as target recognition and reaction units respectively. Glucose can diffuse freely within the hydrogel porous matrix, thereby instigating enzyme-catalyzed reaction that induce alterations in the photothermal effect of the system. This dynamic process ensures efficient and responsive modulation of the system's photothermal properties. By ingeniously capturing distance signals induced by the photothermal effect-mediated water release the visualization and quantification of target substances are achieved, with a linear range spanning from 0 to 30 mM. The consistency between distance-based POCT platform and commercial blood glucose meter demonstrates that the platform provides a portable, affordable and reliable method for visual reading biomarkers. SignificanceThe proposed strategy enables direct, visual quantitative analysis of the target without the need for additional analytical instruments. Particularly, this method holds significant promise as an efficient platform for cholesterol and other disease markers measurement.

Platelet reactivity and activated clotting time predict haemorrhagic site complications in patients with chronic coronary syndromes undergoing percutaneous coronary intervention

Abstract Background/Introduction Same-day discharge has become a standard of care for patients with chronic coronary syndromes (CCS) treated with ad hoc percutaneous coronary interventions (PCI). QuickClot Radial kaolin-based haemostatic device may shorten haemostasis time and reduce the incidence of vascular site complications. Besides unfractionated heparin (UFH) and aspirin (ASA), an ad hoc procedure demands a loading dose of clopidogrel. Dynamic changes in platelets and thrombotic activity may influence the outcomes at vascular sites. Rapid "point-of-care" testing measures the effects of anticoagulation but the optimal threshold during and after PCI still requires further research. Purpose We investigated the effect of a standard dose of UFH and a loading dose of clopidogrel measured with point-of-care devices: Hemochron activated clotting time device (ACT), VerifyNow P2Y12 test on on-site outcomes. Methods We conducted a prospective, observational study of consecutive patients with CCS who qualified for ad hoc PCI. Patients were on chronic ASA therapy, received 100 IU/kg UFH, and a 600 mg loading dose of clopidogrel. ACT was measured before and 10 min, 2 h, and 6 h after the administration of UFH and clopidogrel, respectively, and the VerifyNow P2Y12 test measured after 2 and 6 h. A QuickClot haemostatic pad with gradually released compression for up to 2 h was used in all patients. Ultrasonographic assessment of artery diameter and patency was performed before and 6 h after the procedure. Bleeding (BARC criteria) or local haematoma (EASY scale) were observed regularly until hospital discharge. Results Forty patients were enrolled in the study. The mean±SD age was 68.8±8.8 years, 30 (75%) patients were men, 13 (35%) had diabetes, 38 (95%) hypertension, 16 (40%) previous myocardial infarction, and 15 (37,5%) were active smokers. Patients received a median [interquartile range (IQR)] 8000 [7000-9000] IU of UFH and 600 mg of clopidogrel. All of the radial arteries remained patent during observation; local bleeding (BARC 2) was observed in 11 (27,5%) and haematomas (EASY 1 and 2) in 11 (27,5%) patients. Patients with bleeding had lower platelet activity measured with platelet reactivity units (PRU) after 2 h (122.5± 51 vs 158.7± 43, p= 0.04) and higher ACT (s) (216.9 ±40 vs. 184.6±28 s, p=0.006). An ACT &amp;gt;196 s, measured 2 h after the procedure, predicted the occurrence of bleeding or haematoma (AUC 0.72; 95%CI 0.56-0.85, p=0.008). Conclusion Lower platelet activity and higher ACT after PCI were associated with higher risk of haemorrhagic site complications. "Point-of-care" measures post PCI in CCS patients may be clinically applicable.

Interplay among proton pump inhibitors, platelet reactivity and CYP2C19 genotyping in clopidogrel-treated patients after drug-eluting stent implantation

Abstract Background Several published data suggested that concomitant use of clopidogrel and proton pump inhibitors (PPIs) is associated with reduced antiplatelet efficacy of clopidogrel and increased adverse clinical outcomes. We sought to evaluate the interplay between PPI and clopidogrel on platelet reactivity and long-term clinical outcomes in patients after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation. Methods The PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry is a multi-center, real-world registry of patients who underwent PCI with DES and received dual antiplatelet therapy of aspirin and clopidogrel in South Korea. Patients prescribed with PPI were compared to those without the use of PPI (the control group). The primary outcome was a composite of all-cause death, myocardial infarction, stent thrombosis, and stroke at 5 years. Secondary outcomes included cardiac death, major bleeding, and gastrointestinal bleeding. Adjusted outcomes were compared after 1:2 propensity score (PS) matching analysis. Results Among 13,160 patients, 2235 (17.0%) were prescribed with concomitant PPI at the time of clopidogrel loading. Average age was 64.4 years, 67.2% were men, and 35.1% had diabetes. The PPI group demonstrated a higher on-treatment P2Y12 reaction unit than the control group (p&amp;lt;0.001). The 5-year cumulative incidence of the composite primary outcome was higher in the PPI group (12.1% vs. 9.8%, log-rank p&amp;lt;0.001). After PS matching, the primary outcome was similar between the two groups (12.9% vs. 12.1%, log-rank p=0.24). However, the PPI group with CYP2C19 poor metabolizers showed an increased adjusted risk of the primary outcome (hazard ratio 2.69, p&amp;lt;0.001). Conclusions PPI use in patients with clopidogrel administration after DES implantation was associated with increased platelet reactivity, but similar cardiovascular outcomes in real-world practice. Physicians should be careful when administering PPI with clopidogrel in patients with CYP2C19 poor metabolizers.Distribution of P2Y12 reaction unitCumulative Incidence of outcomes

Impact of kidney function, ticagrelor and genetic polymorphism on high platelet reactivity

Abstract Background High platelet reactivity (HPR) is associated with worse clinical outcomes. Patients with chronic kidney disease (CKD) respond poorly to clopidogrel. The purpose was to investigate what is major determinant on HPR in CKD patients. Methods A total of 219 (139 normal kidney function, 80 CKD) patients who were treated with clopidogrel or ticagrlor were assessed platelet reactivity and genetic polymorphisms. Platelet function was evaluated by the VerifyNowTM P2Y12 assay. Genes tested were ABCB1, PON1, cytochrome P450 (CYP) 2C19, CYP2C9 and P2Y12. HPR was defined as P2Y12 reaction units ≥ 230. Results Platelet reactivity were significantly higher in patients with CKD compared to normal kidney function (288 ± 96 vs 223 ± 69, p &amp;lt; 0.01). But, there were no significant differences of genetic distribution between 2 groups. In patients with CKD and normal kidney function, CYP2C19 carriers had greater platelet reactivity during clopidogrel therapy but there were no differences during ticagrelor treatment regardless of CYP2C19 status (Figure). In multivariate analysis, CKD [hazard ratio (HR): 4.67 (2.27 – 9.78), p &amp;lt; 0.01], CYP2C19 carriers [HR: 2.81 (1.36 – 5.82), p &amp;lt; 0.01] and ticagrelor treatment [HR: 0.29 (0.18 – 0.48), p &amp;lt; 0.01] were significantly correlated with HPR. Conclusion Ticagrelor treatment achieved greater platelet inhibition in patients with CKD whereas CKD and CYP2C19 genotype were significantly correlated with HPR.

Intensity of dual antiplatelet therapy based on thrombotic and bleeding risks after coronary stenting

Abstract Background/Introduction High thrombotic risk (HTR) features are associated with higher ischemic rate, which may be mitigated by potent antiplatelet therapy. However, concomitant high bleeding risk (HBR) may be present, making it unclear whether the intensity of antiplatelet therapy should be prioritized. Purpose This study investigated the prognostic implications of HTR and HBR strata according to intensity of antiplatelet therapy (indicated by platelet reactivity) after coronary stenting. Methods HTR was defined as having at least one of the three risk factors: 1) index presentation with acute coronary syndrome; 2) complex coronary artery disease and stenting; and 3) guideline-directed clinical ischemic risk factors. HBR was determined according to presence of Academic Research Consortium (ARC)-HBR criteria. In addition, high platelet reactivity (HPR) was decided depending on the level of platelet reactivity (&amp;gt; 208 P2Y12 reaction unit measured by VerifyNow assay). Results Among 4,550 patients, HTR features were observed in 3,973 patients (87.3%) and 1,451 (31.9%) met the ARC-HBR criteria. HPR phenotype (n=2563, 56.3%) significantly increased the risk of 4-year ischemic events (adjusted hazard ratio [HRadj]: 1.40; 95% confidence interval [CI]: 1.15-1.70; P=0.001). Among patients who met the ARC-HBR criteria, HPR was not associated with the rate of ischemic events, regardless of HTR features. In cases of non-HBR patients, HPR phenotype increased ischemic events only in patients with HTR feature(s), which risk proportionally increased according to the number of HTR features (HRadj: 0.67, 1.47 and 1.58; 95% CI: 0.22-2.08, 0.94-2.29 and 1.09-2.28 in 0 [9.2%], 1 [31.2%] and ≥2 [27.7%] HTR features). In HBR patients, the risk of major bleeding was not increased by the level of antiplatelet effect. Conclusion HPR phenotype was significantly associated with the risk of ischemic events after coronary stenting, which proportionally increased according to the number of HTR features only if the ARC-HBR criteria were not present. These observations suggested that when concordant, bleeding risk, more than ischemic risk, should inform decision-making on the intensity of antiplatelet therapy.KM curve and HR forest plot for MACCEKM curve and HR forest plot for NACE

Association between high platelet reactivity and early stent thrombosis in patients with drug-eluting stent implantation

Abstract Background Stent thrombosis (ST) is a potentially fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence is not fully elucidated. Methods Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were identified. The independent predictors of early stent thrombosis (EST) were assessed. The primary outcome after EST was the composite of cardiac death, myocardial infarction and any revascularisation. Key secondary outcomes were all-cause death, cardiac death, myocardial infarction, and any revascularisation. Results EST, defined as definite ST in less than 1 month after index PCI, was identified in a total of 51 patients. The PRU value was significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p&amp;lt;0.001). In multivariable analysis, having a PRU value of ≥252 (OR, 5.10; 95% CI, 1.58-16.46; p=0.006) and an ARU value of ≥414 (OR 4.85; 95% CI, 1.07-21.97; p=0.040) were significant predictors of EST. The use of first-generation DES (OR 3.56; 95% CI, 0.98-12.99; p=0.054) also posed a higher risk for EST occurrence with a borderline significance. Cumulative incidence of the primary composite outcome was significantly higher in patients with EST (HR 18.7; 95% CI 12.8-27.3; p&amp;lt;0.001). Conclusion In patients treated with clopidogrel after successful DES implantation, EST was associated with higher PRU values, and a greater rate of adverse outcomes, including all-cause death and MI.

Abstract 13963: Redefining the Assessment of “Therapeutic” Platelet Response to Acetylsalicylic Acid

Background: Despite extensive investigations, the optimal assessment of the “therapeutic response” to acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between serum thromboxane (Tx)B 2 ; arachidonic acid (AA)-induced platelet aggregation (PA) by light transmittance aggregometry (LTA); aspirin reaction units (ARU) by VerifyNow aspirin test (VN), and pharmacokinetics (PK). Methods: Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy volunteers. ASA response was defined as &gt;95% inhibition of serum TxB 2, &lt;550 ARU by VN test and ≤20% AA-induced PA. Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. Results: ASA Response measured by VN, and AA-induced PA was achieved within 30 minutes of ASA administration. A good correlation was observed between VN ARU and 1 mM AA-induced maximum PA (r=0.80, p&lt;0.001), serum TxB 2 (r=0.76, p&lt;0.001), and inhibition of serum TxB 2 (r=0.87, p&lt;0.001). The relation between platelet aggregation and TxB 2 inhibition appears to be dichotomous, with only modest inhibition of TxB 2 (~50% inhibition) associated with marked inhibition of platelet aggregation. ROC curve analyses indicated that ≤558 ARU and ≤7% AA-induced PA were associated with &gt;95% inhibition of TxB 2 . A plasma ASA 686 ng/mL cut-off was associated with &gt;95% inhibition of serum TxB 2 , ≤7% 1 mM AA-induced PA by LTA, and ≤585 ARU. Conclusion: Our study demonstrated an important relationship between PD and PK parameters measured immediately following oral ASA and cutoff values for VN assay and LTA that is associated with &gt;95% inhibition of serum TxB 2 . We demonstrated that ~50% inhibition of TxB 2 is required to reach high levels of platelet function inhibition.