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BACKGROUND This study assessed the association between a novel inflammatory marker, uric acid (UA)-to-albumin ratio (UAR), and preprocedural intracoronary artery thrombus (ICAT) in ST elevation myocardial infarction (STEMI). MATERIAL AND METHODS A total of 171 STEMI patients treated by primary percutaneous coronary intervention between February and December 2023 were evaluated prospectively in this cross-sectional study. The patients were stratified into 2 groups as low (grades 1 to 3) and high-(ICAT) groups (grades 4 and 5). To determine the independent predictors of lower and higher ICAT, multivariate regression analysis was performed. RESULTS C-reactive protein (CRP), UA, and UAR were significantly higher in the high ICAT group (1.11 (0.3-2.8) vs 0.80 (0.10-2.8), P=0.037; 5.4 (3.5-7.2) vs 4.9 (3.4-5.6), P<0.001; 1.78 (0.82-3) vs 1.48 (0.77-2.57), P<0.001, respectively). However, albumin levels were similar between groups (3.1 (2.1-4.4) vs 3.3 (2.1-4.4), P=0.243). Higher UAR (OR: 3.95% CI: 1.23-12.7, P=0.021), lower left ventricular ejection fraction (LVEF) (OR=0.802; 95% CI 0.7537-0.872; P<0.001), longer pain-wire crossing time (OR=1; 95% CI: 1-1.02; P<0.001), and diabetes mellitus (OR=0.181; 95% CI 0.46-0.7; P<0.001) were independent predictors of ICAT. CONCLUSIONS UAR, a marker of inflammation, is an independent predictor of ICAT in patients with STEMI.

The blood glucose level at admission indicates (with some limitations) poor prognosis and thrombus burden in patients with the acute coronary syndrome (ACS). Our study aimed to measure the predictive value of the stress hyperglycemia ratio (SHR), an indicator of stress hyperglycemia, showing increased thrombus burden in patients with ACS. Patients (n = 1222) with ACS were enrolled in this cross-sectional study. Coronary thrombus burden was classified as high and low. SHR was calculated by dividing the admission serum glucose by the estimated average glucose derived from HbA1c. Low thrombus burden was detected in 771 patients, while high thrombus burden (HTB) was detected in 451 patients. SHR was found to be significantly higher in patients with HTB (1.1 ± .3 vs 1.06 ± .4; P = .002). SHR was determined as a predictor of HTB (odds ratio (OR) 1.547 95% CI (1.139-2.100), P < .001) as a result of univariate analysis. According to multivariate analysis, SHR was determined as an independent risk factor for HTB (OR 1.328 CI (1.082-1.752), P = .001). We found that SHR predicted thrombus burden with higher sensitivity than admission glucose level in patients with ACS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The high thrombus burden of the infarct-related artery (IRA) is associated with the adverse prognosis in ST-segment elevation myocardial infarction (STEMI) patients. Our objectives were to investigate the predictors and evaluate the prognosis of refractory thrombus in STEMI patients. A total of 1305 consecutive patients with STEMI who underwent primary percutaneous coronary intervention (pPCI) were screened. The refractory thrombus group (n = 15) was defined as IRA thrombolysis in myocardial infarction flow < grade 2 after multiple thrombus aspiration (TA). The control group (n = 45) was age- and sex-matched and was selected from the same batch of patients. Baseline hematologic indices were measured before the pPCI. The major adverse cardiovascular events (MACE) were recorded during follow-up. The refractory thrombus group had significantly higher red cell distribution width (RDW) at baseline compared with the control group (13.1 [12.4-13.7] vs 12.6 [12.3-12.8], P = .008). In multivariate logistic regression analysis, RDW was an independent predictor of refractory thrombus (odds ratio: 8.799, 95% CI: 1.240-62.454, P = .030). The area under the receiver-operating characteristic curve of the RDW was 0.730 (95%CI: 0.548-0.912, P = .008). During a mean period of 26 months follow-up, patients in the refractory thrombus group tended to have higher percent MACEs compared with patients in the control group (53.3% vs 6.7%, P < .001). In the present study, we found that the refractory thrombus in STEMI patients was associated with the worse prognosis and the increased RDW might be a potential independent predictor., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

An 86-year-old man successfully underwent percutaneous coronary intervention (PCI), in which a drug-coated stent (DCS) was placed in the left anterior descending coronary artery. However, stent thrombosis occurred twice after eight and two months. After the second admission, the patient was tested for platelet aggregation activity using the platelet aggregation threshold index (PATI), and insufficient inhibition of platelet aggregation was observed. The patient's PATI improved to a satisfactory level using oral anticoagulants. At the six-month follow-up, clinical events were observed. Measuring the platelet aggregation ability can help clinicians understand the pathology of patients and determine treatment choices.

Aim: to investigate whether the MAPH score, which is a new score that combines blood viscosity biomarkers such as mean platelet volume (MPV), total protein and hematocrit, can be used to predict thrombus burden in ST-segment elevation myocardial infarction (STEMI) patients., Methods: A total of 473 consecutive patients with STEMI were included in the study. Intracoronary tirofiban/abciximab infusion was applied to patients with thrombus load ≥3 and these patients (n = 71) were defined as the patient group with high thrombus load. MPV, age, hematocrit and total protein values of the patients were recorded. High shear rate (HSR) and low shear rate (LSR) were calculated from total protein and hematocrit values. Cut-off values were determined for high thrombus load by using Youden index, and score was determined as 0 or 1 according to cut-offs. The sum of the scores was calculated as the MAPH score., Results: The mean age of the patients included in the study was 59.6 ± 12.6 (n = 354 male, 74.8%). There was no difference between the groups in terms of gender, HT and DM ( P  = .127, P  = .402 and P  = .576, respectively). In the group with high thrombus load; total protein, MPV and hematocrit values were higher ( P  < .001, P  = .001 and P  = .03, respectively). Comparison of receiver operating characteristic (ROC) curve analysis revealed that the MAPH score had better performance in predicting higher thrombus load than both other self-containing parameters and HSR and LSR., Conclusion: The MAPH score may be a new score that can be used to determine thrombus burden in STEMI patients.

The development of an obstructive luminal thrombus is pathological and considered a failure of endogenous fibrinolysis. The consequences may be fatal, or result in lasting downstream organ damage. Therefore, assessment of endogenous fibrinolytic status in an individual may identify those at risk of occlusive thrombus formation and provide prognostic information. Arterial thrombi are more platelet rich and more resistant to fibrinolysis than venous thrombi. Several recent studies using global tests of fibrinolysis in patients with acute coronary syndromes (ACS) have shown that despite dual antiplatelet therapy, patients with impaired fibrinolytic status have an increased risk of adverse cardiovascular events, compared with those with effective fibrinolytic function. Such data add significantly to the predictive value of established cardiovascular risk factors and conventional biomarkers. Most data reported have been obtained with the Global Thrombosis Test and the turbidimetric plasma clot lysis assay. A few small studies in patients with ischaemic stroke suggest a similar predictive role of fibrinolytic status assessment in these patients. Studies reporting an association between impaired fibrinolysis and future venous thrombotic events are limited, and in the form of case-control studies. Viscoelastic assays may have a role in the prediction of venous thromboembolic risk. Assays of fibrinolytic function should be used to obtain a more accurate risk of future thrombotic events, particularly in the setting of ACS. The availability of point-of-care tests helps facilitate this and should encourage future studies to assess personalised antithrombotic treatment combinations to optimise fibrinolytic status and reduce thrombosis risk., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Coronavirus disease-2019 (COVID-19) is thought to predispose patients to thrombotic disease. To date there are few reports of ST-segment elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in patients with COVID-19., Objectives: The aim of this study was to describe the demographic, angiographic, and procedural characteristics alongside clinical outcomes of consecutive cases of COVID-19-positive patients with STEMI compared with COVID-19-negative patients., Methods: This was a single-center, observational study of 115 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention at Barts Heart Centre between March 1, 2020, and May 20, 2020., Results: Patients with STEMI presenting with concurrent COVID-19 infection had higher levels of troponin T and lower lymphocyte count, but elevated D-dimer and C-reactive protein. There were significantly higher rates of multivessel thrombosis, stent thrombosis, higher modified thrombus grade post first device with consequently higher use of glycoprotein IIb/IIIa inhibitors and thrombus aspiration. Myocardial blush grade and left ventricular function were significantly lower in patients with COVID-19 with STEMI. Higher doses of heparin to achieve therapeutic activated clotting times were also noted. Importantly, patients with STEMI presenting with COVID-19 infection had a longer in-patient admission and higher rates of intensive care admission., Conclusions: In patients presenting with STEMI and concurrent COVID-19 infection, there is a strong signal toward higher thrombus burden and poorer outcomes. This supports the need for establishing COVID-19 status in all STEMI cases. Further work is required to understand the mechanism of increased thrombosis and the benefit of aggressive antithrombotic therapy in selected cases., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been associated with numerous pathophysiological sequelae, including large artery vasospasm and microvascular thrombosis. The focus of this review is to provide an overview of experimental animal model studies and human autopsy studies that explore the temporal-spatial characterization and mechanism of microvascular platelet aggregation and thrombosis following SAH, as well as to critically assess experimental studies and clinical trials highlighting preventative therapeutic options against this highly morbid pathophysiological process. Upon review of the literature, we discovered that microvascular platelet aggregation and thrombosis occur after experimental SAH across multiple species and SAH induction techniques in a similar time frame to other components of DCI, occurring in the cerebral cortex and hippocampus across both hemispheres. We discuss the relationship of these findings to human autopsy studies. In the final section of this review, we highlight the important therapeutic options for targeting microvascular platelet aggregation and thrombosis, and emphasize why therapeutic targeting of this neurovascular pathology may improve patient care. We encourage ongoing research into the pathophysiology of SAH and DCI, especially in regard to microvascular platelet aggregation and thrombosis and the translation to randomized clinical trials.

Long-standing aspirin is the cornerstone to prevent recurrence of thrombotic events in patients with ischemic heart disease. However, clopidogrel, a more potent antiplatelet agent, is preferred over aspirin in targeted populations, including those with a high risk of gastrointestinal bleeding. In addition, clopidogrel offers superior oral tolerance, and it may reduce the rates of intracranial hemorrhages compared with aspirin. However, an extensive inhibition of the coagulation cascade seems to be reasonable to minimize thrombotic events in such patients. After several failed exploratory investigations in the past with vitamin K antagonists, the newest direct oral anticoagulants may represent an alternative. To counterbalance bleeding complications, a low dose of these agents should be considered. Few publications have already showed promising results with the combination of clopidogrel and low-dose direct oral anticoagulants. Further investigations should be addressed to elucidate whether this is the downfall of the aspirin era for secondary prevention of atherosclerotic cardiovascular events.

Background: Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome., Objectives: We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI)., Methods: We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR., Results: Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis., Conclusion: In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis., (© 2019 Aix-Marseille University. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc.)

Background: Smoking is a potent risk factor for coronary artery disease; however, prior studies describe increased platelet inhibition with clopidogrel among smokers, and some studies report improved outcomes among smokers, a finding described as the smoker's paradox. This study assessed the relationship between platelet reactivity and clinical outcomes after percutaneous coronary interventions among current smokers and nonsmokers., Methods: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. Platelet reactivity was assessed by the VerifyNow point-of-care assay; high on-treatment platelet reactivity (HPR) was defined as P2Y12 reaction units >208. A propensity-adjusted multivariable analysis was performed to determine the relationship between current smoking, platelet reactivity, and subsequent adverse events., Results: Among 8582 patients, 22.6% were active smokers at the time of their percutaneous coronary intervention procedure. Current smokers were younger and had fewer comorbidities compared with nonsmokers. Current smokers had lower mean P2Y12 reaction units and lower rates of HPR compared with nonsmokers. Current smokers had similar rates of adverse events compared with nonsmokers. HPR was associated with higher rates of adverse events for both smokers and nonsmokers; however, there was evidence of interaction between smoking status and the effect of HPR. Smokers with HPR had significantly higher rates of stent thrombosis. Adverse event rates were highest among current smokers with HPR., Conclusions: Current smoking was associated with lower P2Y12 reaction units and lower rates of HPR on average; however, the combination of current smoking and HPR was associated with high rates of stent thrombosis., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Small vessel diameter and residual platelet reactivity are independent predictors of thrombotic events after percutaneous coronary intervention (PCI). We sought to determine whether an interaction exists between residual platelet reactivity and stent diameter regarding the occurrence of stent thrombosis and other adverse events after PCI. We stratified patients in the prospective ADAPT-DES registry who underwent single-lesion PCI according to if they received a small diameter stent (SDS, defined as a stent with a diameter of 2.25 mm). Patients receiving an SDS were compared with patients receiving a stent ≥2.5 mm using Kaplan-Meier rates and multivariable Cox proportional hazards regression. We defined major adverse cardiac events (MACE) as the composite of cardiac death, myocardial infarction, and stent thrombosis (ST). Among 5,608 patients who underwent single-lesion PCI in ADAPT-DES, 222 (4.0%) patients received an SDS. Patients with an SDS were more likely than patients without an SDS to have 3-vessel disease but received, on average, fewer stents and were less likely to present with a thrombotic lesion. Receiving versus not receiving an SDS was associated with increased risk of ST (adjusted hazard ratio 4.35, 95% confidence interval 1.95 to 9.73, p <0.001) as well as MACE (adjusted hazard ratio 1.75, 95% confidence interval 1.11 to 2.75, p = 0.02). There was no statistical interaction between platelet reactivity and SDS regarding ST (p = 0.12) or MACE (p = 0.51). In conclusion, PCI with small drug-eluting stents is associated with a high risk of thrombotic events, including ST. Further studies should explore whether alternative treatment strategies are appropriate in small vessels., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In the ARCTIC trial (Assessment by a Double Randomization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting), treatment adjustment following platelet function testing failed to improve clinical outcomes. However, high-on-treatment platelet reactivity (HPR) is considered as a predictor of poor ischemic outcome. This prespecified substudy evaluated clinical outcomes according to the residual platelet reactivity status after antiplatelet therapy adjustment., Methods: We analyzed the 1213 patients assigned to the monitoring arm of the ARCTIC trial in whom platelet reactivity was evaluated by the VerifyNow P2Y 12 test before percutaneous coronary intervention and during the maintenance phase (at 14 days). HPR was defined as platelet reaction unit≥235U. The primary ischemic end point, a composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization and the safety end point of major bleeding were assessed according to the platelet reactivity status., Results: Before percutaneous coronary intervention, 35.7% of patients displayed HPR (n=419). During the acute phase, between percutaneous coronary intervention and the 14-day platelet function testing, ischemic (adjusted hazard ratio, 0.94 [95% CI, 0.74-1.18]; P =0.58) and safety outcomes (hazard ratio, 1.28 [95% CI, 0.22-7.59]; P =0.78) were similar in HPR and non-HPR patients. During the maintenance phase, the proportion of HPR patients (n=186, 17.4%) decreased by 56%. At 1-year, there was no difference for the ischemic end point (5.9% versus 6.0%; adjusted hazard ratio, 0.79 [95% CI, 0.40-1.58]; P =0.51) and a nonsignificant higher rate of major bleedings (2.7% versus 1.0%, hazard ratio, 2.83 [95% CI, 0.96-8.41]; P =0.06) in HPR versus non-HPR patients., Conclusions: The proportion of HPR was halved after platelet function testing and treatment adjustment but without significant ischemic benefit at 1 year. HPR seems more as a modifiable risk marker than a risk factor of ischemic outcome., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00827411.

Background: It is unclear whether high platelet count or high hematocrit predict risk of thrombosis in individuals from the general population., Objectives: We tested the hypothesis that individuals from the general population with high platelet count or high hematocrit have high risk of arterial and venous thrombosis., Methods: We prospectively followed 108 521 individuals from The Copenhagen General Population Study for a median of 8 years. Platelet count and blood hematocrit were measured at study entry., Results and Conclusion: Multivariable adjusted hazard ratios for individuals with platelet counts in the top 5 percentiles (>398 × 10 9 /L) vs in the 25th-75th percentiles (231-316 × 10 9 /L) were 1.77 (95% confidence interval [CI], 1.38-2.24) for arterial thrombosis in the brain (38 and 26 events/10 000 person-years) and 0.82 (95%, 0.61-1.11) for arterial thrombosis in the heart (23 and 28 events/10 000 person-years). For individuals with hematocrit values in the top 5 percentiles (women/men: >45/>48%) vs the 25th-75th percentiles (women/men: 38.1-42/41.1-45%), hazard ratios were 1.27 (95% CI, 0.91-1.75) for arterial thrombosis in the brain (40 and 26 events/10 000 person-years) and 1.46 (95% CI, 1.06-2.00) for arterial thrombosis in the heart (43 and 25 events/10 000 person-years). Neither high platelet count nor high hematocrit was associated with risk of venous thromboembolism. When excluding individuals with myeloproliferative neoplasia from the main analyses, results on risk of thrombosis were similar. In this prospective study, high platelet counts were associated with 1.8-fold risk of arterial thrombosis in the brain, whereas high hematocrit was associated with 1.5-fold risk of arterial thrombosis in the heart., (© 2019 International Society on Thrombosis and Haemostasis.)

A 27-year-old elite-level professional cyclist presented to the emergency department with a 6-hour history of chest pain and vomiting after prematurely aborting a competitive event. ECG demonstrated anterior ST segment elevation myocardial infarction, and blood tests revealed a grossly elevated high-sensitivity troponin T. Emergent coronary angiography confirmed the presence of a thrombus in the mid-left anterior descending artery with possible spontaneous coronary artery dissection. The patient recovered well following balloon angioplasty and thrombus aspiration, despite delayed recognition, invasive investigation and intervention., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y 12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y 12 -inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early- vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention-treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Purpose- Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods- As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results- One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P=0.005) and percentage of platelet content (22.1±4.2% versus 13.9±14.2%; P=0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P=0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P=0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions- High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.

We hypothesized that the combination of a high neutrophil to lymphocyte ratio (NLR) and mean platelet volume (MPV) would be a stronger predictor of future cardiovascular events after percutaneous coronary intervention (PCI). Both NLR and MPV were measured in 364 consecutive patients undergoing PCI. The primary end point was the incidence of major adverse cardiovascular events (MACEs), including cardiac death, nonfatal myocardial infarction, and stent thrombosis. The median values of NLR and MPV were 2.8 and 8.2 fL, respectively. There were 26 MACEs during a median follow-up duration of 29.3 months. Kaplan-Meier analysis revealed that the higher NLR group had a significantly higher MACE rate than the lower NLR group and that the higher MPV group had a significantly higher MACE rate than the lower MPV group (log-rank: P = .0064 and P = .0004, respectively). The cumulative MACE-free survival can be further stratified by the combination of NLR and MPV. This value was especially useful in patients with acute coronary syndrome (ACS). By multivariate Cox proportional hazards model, the combination of high NLR and high MPV was independently associated with MACE ( P = .026). The combination of a high NLR and high MPV is an independent predictor of MACE after PCI, especially in patients with ACS.

Although coronary thrombosis (CT) is integral to cardiovascular outcomes, the underlying pathophysiological mechanisms remain unclear. CT may occur in case of atherosclerotic plaque erosion/rupture, or even after stenting implantation. Platelets (PLT) activation is the keystone of atherothrombosis and depends on many dysregulated elements, including endothelial dysfunction, oxidized lipoproteins, and immune response. Besides the classical view of PLT as an effector of hemostatic response, a new repertoire of PLT activities is emerging. PLT lipidome oxidation is a self-maintaining process which promotes PLT reactivity, coagulation cascade, and inflammatory cell activation. PLT-innate immune cell interaction is also sustained by neutrophil extracellular traps and NLRP3 inflammasome pathways. Other noteworthy emerging mechanisms are implicated in the crosstalk between PLT and surrounding cells. Especially, microvesicles (MVs) released from PLT may extend their signaling network far beyond the classical cell-cell interactions. Moreover, the recognition of noncoding RNA in PLT MVs introduce another layer of complexity in terms of intercellular signaling by a direct regulation of messenger RNA profile and gene expression in the recipient cells. The aim of this narrative review is to update the recent advance in CT and intracoronary stent thrombosis, including causal factors and potential translation of experimental evidence into the clinical setting., (© 2018 Wiley Periodicals, Inc.)

Allergic, IgE-mediated inflammation is thought to play a role in atherogenesis and atherosclerotic disease progression. In this study, total IgE and mast cell tryptase were measured in a series of forensic autopsy cases including non-allergic cardiac deaths (14 cases with minimal or no coronary atherosclerosis, 14 cases with significant coronary artery atherosclerosis without acute coronary thrombosis, and 14 cases with significant coronary artery atherosclerosis and acute coronary thrombosis or myocardial infarction) and non-allergic non-cardiac deaths (21 cases with death due to hanging and 21 cases with death due to intracranial gunshot wounds), in order to correlate laboratory results with morphological findings and compare them to conclusions reported in the clinical setting. In cardiac death cases, postmortem serum total IgE levels were increased in 7 out of 42 cases and mast cell tryptase levels were increased in 3 out of 42 cases. In non-cardiac death cases, postmortem serum total IgE levels were not increased in 39 out of 42 cases and mast cell tryptase levels were not increased in any of these cases. These preliminary findings seem to indicate that a portion of coronary deaths characterized by coronary artery atherosclerosis of various severities are also characterized by increased total IgE and mast cell tryptase levels, thus corroborating the data previously reported in both clinical and forensic literature on this topic as well as the necessity of combining morphological investigations focusing on the heart and coronary arteries with biochemical analyses., (Copyright © 2018. Published by Elsevier Ltd.)

Shortly after the discovery that linoleic acid was an essential fatty acid in 1930, α-linolenic acid also was reported to prevent the fatty acid deficiency syndrome in animals. However, several prominent laboratories could not confirm the findings with α-linolenic acid, and as a result there was a loss of interest in omega-3 fatty acids in lipid research. Even the findings that a prostaglandin can be synthesized from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is necessary for optimum retinal function generated only limited interest in omega-3 fatty acids. The breakthrough came in the 1970s when Dyerberg and Bang reported that the low incidence of atherosclerotic coronary disease in Greenland Eskimos was due to the high marine lipid content of their diet. They subsequently found that EPA, which was increased in Eskimo plasma, inhibited platelet aggregation, and they concluded that the low incidence of coronary artery disease was due to the anti-thrombotic effect of EPA. This stimulated widespread interest and research in EPA and DHA, leading to the present view that, like their omega-6 counterparts, omega-3 fatty acids have important physiological functions and are essential fatty acids., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Increased coronary thrombus burden is known to be a strong predictor of adverse cardiovascular (CV) outcomes. C-reactive protein to albumin ratio (CAR) can be used as a surrogate marker of pro-inflammation which is closely related to prothrombotic state. We aimed to evaluate the association between CAR and coronary thrombus burden in patients who presented with acute coronary syndrome (ACS). Patients who presented with ACS and treated with primary percutaneous coronary intervention were included in the study. Patients were divided into 2 groups as high thrombus burden and low thrombus burden. The study population included 347 patients with non-ST-segment elevation myocardial infarction (169 [48.7%]) and ST-segment elevation myocardial infarction (178 [51.3%]). The CAR was significantly higher in patients with higher thrombus burden (24.4 [1.2-30.2] vs 31.9 [2.2-31.3], P < .001). Independent predictors for increased thrombus burden were higher CRP level (odds ratio [OR]: 0.047; 95% confidence interval [CI]: 0.004-0.486; P = .010), lower serum albumin level (OR: 0.057; 95% CI: 0.033-0.990; P = .049), higher CAR (OR: 1.13; 95% CI: 1.03-1.23; P = .008), higher neutrophil-lymphocyte ratio (OR: 1.18; 95% CI: 1.05-1.31; P = .004), and baseline troponin I level (OR: 1.06; 95% CI: 1.01-1.13; P = .017). Novel CAR can be used as a reliable marker for increased coronary thrombus burden that is associated with adverse CV outcomes.

Background: For patients who have an indication for anticoagulation, it is controversial whether dual therapy with an oral anticoagulant and single antiplatelet agent can be used after percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) instead of triple therapy with an oral anticoagulant and dual antiplatelet therapy., Participants and Methods: Twelve observational studies and four clinical trials were identified from three electronic databases from their inception to December, 2017. Pooled estimates were calculated using a random-effects model for meta-analysis., Results: Compared with the triple therapy, dual therapy was associated with significantly lower risk of major bleeding [relative risk (RR), 0.63; 95% confidence interval (CI), 0.50-0.80] without statistically significant increase in major adverse cardiac events (RR, 1.04; 95% CI, 0.84-1.29), all-cause death (RR, 1.15; 95% CI, 0.77-1.71), cardiac death (RR, 1.04; 95% CI, 0.67-1.61), myocardial infarction (RR, 1.25; 95% CI, 0.98-1.59), stroke (RR, 1.27; 95% CI, 0.79-2.06), stent thrombosis (RR, 1.52; 95% CI, 0.96-2.41), and repeat revascularization (RR, 1.15; 95% CI, 0.87-1.52). Although risks of myocardial infarction and stent thrombosis were marginally higher in the dual therapy group, this trend was attenuated after excluding studies that exclusively included patients undergoing PCI for ACS, but not stable coronary artery disease., Conclusion: Dual therapy may be a reasonable alternative to triple therapy after PCI in patients with indication for chronic anticoagulation. However, further studies are needed to investigate efficacy of dual therapy, especially in the patients with higher ischemic risk, such as in ACS.

Background: Randomised controlled trials have provided conflicting results regarding procedural and clinical outcomes of thrombus aspiration combined with percutaneous coronary intervention, when compared with primary percutaneous coronary intervention alone in patients with acute coronary syndromes., Methods: Acute coronary syndrome patients referred for coronary angiography to four Swiss university hospitals between 2009 and 2012 were enrolled in the SPUM-ACS cohort. At the discretion of the interventional cardiologist, patients underwent thrombus aspiration with percutaneous coronary intervention or percutaneous coronary intervention alone. Procedural success was defined as post-procedural thrombolysis in myocardial infarction III flow in the infarct-related artery. Serial changes in high-sensitivity troponin T (ΔhsTnT) and adjudicated 30 days (1 year) clinical events defined as the composite of cardiac death, recurrent myocardial infarction or clinically indicated coronary revascularisation were assessed., Results: Among 1641 patients, 777 (47.4%) had angiographic evidence of coronary thrombus. Patients were categorised into thrombus aspiration with percutaneous coronary intervention ( n=663) or percutaneous coronary intervention alone ( n=114). ST-segment elevation myocardial infarction (STEMI) patients more often received thrombus aspiration with percutaneous coronary intervention (87.8%) than non-STEMI patients (73.5%), P<0.001. Procedural success was not different in thrombus aspiration with percutaneous coronary intervention compared with percutaneous coronary intervention alone (93.8% vs. 90.7%, P=0.243). ΔhsTnT was similar in STEMI patients (3.09±4.52 vs. 2.19±4.92 µg/l, P=0.086) as was clinical outcome in the entire cohort at 30 days (2.9% vs. 3.6%, P=0.76) and 1 year (7.2% vs. 5.3%, P=0.55) regardless of whether thrombus aspiration was used during primary percutaneous coronary intervention or not., Conclusions: In this real-world acute coronary syndrome cohort, patients treated by thrombus aspiration with percutaneous coronary intervention showed no difference in the restoration of coronary blood flow compared with percutaneous coronary intervention alone immediately after the procedure. Furthermore, ΔhsTnT and clinical outcomes at either 30 days or 1 year were similar between thrombus aspiration with percutaneous coronary intervention or percutaneous coronary intervention alone., Clinical Trials Registration: SPUM-ACS cohort NCT01000701.

The optimal antithrombotic treatment regimen for patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation represents a challenge in clinical practice. In 2016, an updated opinion of selected experts from the United States and Canada on the treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention was reported. After the 2016 North American consensus statement on the management of antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention, results of pivotal clinical trials assessing the type of oral anticoagulant agent and the duration of antiplatelet treatment have been published. On the basis of these results, this focused update on the antithrombotic management of patients with atrial fibrillation undergoing percutaneous coronary intervention recommends that a non-vitamin K antagonist oral anticoagulant be preferred over a vitamin K antagonist as the oral anticoagulant of choice. Moreover, a double-therapy regimen (oral anticoagulant plus single antiplatelet therapy with a P2Y 12 inhibitor) by the time of hospital discharge should be considered for most patients, whereas extending the use of aspirin beyond hospital discharge (ie, triple therapy) should be considered only for selected patients at high ischemic/thrombotic and low bleeding risks and for a limited period of time. The present document provides a focused updated on the rationale for the new expert consensus-derived recommendations on the antithrombotic management of patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention.

Delayed onset of action of oral P2Y 12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2-3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y 12 inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y 12 inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y 12 inhibition., Competing Interests: R.F.S. reports research grants from AstraZeneca, PlaqueTec; Honoraria from AstraZeneca; Consultant/Advisory Board fees from AstraZeneca, Actelion, Avacta, Bayer, Bristol Myers Squibb/Pfizer, Idorsia, Novartis and The Medicines Company. Other authors have no disclosures., (Georg Thieme Verlag KG Stuttgart · New York.)

Platelet activation and aggregation play a pivotal role in thrombotic complications occurring during percutaneous coronary intervention (PCI), and peri-PCI anti-platelet therapy represents a standard of care. High platelet reactivity prior to PCI has been correlated with an increased incidence of peri-procedural myonecrosis. Pre-PCI platelet reactivity predicts post-PCI platelet reactivity and has a prognostic impact on subsequent ischaemic and bleeding events, so as the platelet inhibition measured post-PCI. Many anti-platelet treatment strategies, including aspirin, glycoprotein IIb/IIIa inhibitors, P2Y 12 receptor blockers and vorapaxar, are being used in the routine clinical practice to modify platelet reactivity at each stage, e.g. pre-, during and post-PCI. Anti-platelet strategies with a 'stronger and faster' pharmacodynamic effect than clopidogrel have been mostly adopted in patients with acute coronary syndromes. However, several issues regarding the anti-platelet treatment such as benefits/risks of anti-platelet therapy pre-treatment and duration, and definite association between speed and potency of various anti-platelet agents and clinical outcomes remain controversial. We believe that a better understanding of peri-PCI platelet reactivity and its relations to outcomes may lead to the development of more effective and safe treatment strategies., Competing Interests: Dr Alexopoulos reports advisory board fees (modest) from AstraZeneca, Boehringer Ingelheim, Bayer, Medtronic and speaker honoraria (modest) from AstraZeneca, Bayer and Boehringer Ingelheim. Dr Gurbel reports personal fees (modest) from AstraZeneca, Boehringer Ingelheim, Merck, Janssen Pharmaceuticals, New Haven Pharmaceuticals, Bayer and Haemonetics; grants (modest) from Haemonetics, Merck, Duke Clinical Research Institute, Harvard Clinical Research Institute, National Institutes of Health, Coramed Technologies, MedImmune and Sinnowa; Dr Gurbel has a patent for platelet function testing. Other authors have no conflicting interests., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Early escalation from clopidogrel to new generation P2Y12 inhibitors is common practice in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Real-world data about this strategy, however, are limited., Methods: From 2012 to 2015, 1,057 consecutive STEMI patients treated with pPCI in an Italian hub-and-spoke network were prospectively included in an observational registry (RENOVAMI, ClinicalTrials.gov Identifier: NCT01760382). We compared the prevalence, predictive factors and in-hospital outcomes of patients escalated to a new generation P2Y12 inhibitor within the first 24 hours from pPCI with those continuing on admission antiplatelet therapy., Results: In the first 24 hours after pPCI, 165 patients (15.6%) were escalated from clopidogrel to a new generation P2Y12 inhibitor, while de-escalation to clopidogrel was occasional (19 patients, 1.8%) and switch between new generation P2Y12 inhibitors was rare (8 patients, 0.8%, all from ticagrelor to prasugrel). Drug eluting stent use (adjusted odds ratio [OR], 2.19, 95% confidence interval [CI], 1.55-3.08, p  = 0.0002) and impaired renal function (adjusted OR, 0.19, 95% CI, 0.05-0.77, p  = 0.02) were the only independent predictive factors for the decision to escalate. After adjustment for potential confounders, escalation did not predict in-hospital outcomes, whereas the overall use of new generation P2Y12 inhibitors was correlated with a better in-hospital survival (adjusted hazard ratio, 0.47, 95% CI, 0.25-0.91, p  = 0.03). Moreover, escalation did not influence bleeding rates., Conclusions: In this prospective registry of STEMI patients treated with pPCI and contemporary antiplatelet therapy, early escalation to a new generation P2Y12 inhibitor appeared safe and did not significantly affect in-hospital bleeding rates., Competing Interests: None., (Schattauer GmbH Stuttgart.)

Background: Early stent thrombosis (ST) remains an important complication of primary percutaneous intervention (PCI). To date, our information on angiographic and clinical predictors of early ST in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI is limited., Methods: We tried to evaluate the incidence, predictors, and outcomes of early ST in real-world patients treated with primary PCI. We identified all the patients presenting with STEMI between June 2004 and January 2011 who underwent primary PCI as the primary mode of revascularization. Diagnosis of ST was made as per the standard definition proposed by the Academic Research Consortium., Results: The incidence of early ST was 1% among 2,303 patients treated with primary PCI. Definite and probable early ST occurred in 22 and 2 patients, respectively. Patients with early ST had higher in-hospital (P = 0.03) and 30-day mortality (P = 0.048). The rate of cardiogenic shock (P = 0.0006) and cerebrovascular accident (P = 0.0004) was also greater in the early ST group. Smaller stent diameter and lower use of intracoronary glycoprotein IIb/IIIa inhibitor were associated with higher rate of early ST. There was a trend of higher bivalirudin use in ST group, which did not reach significance (P = 0.07) On IVUS imaging, stent malapposition and uncovered plaque area were noted in 6 out of 11 cases., Conclusion: The incidence of early ST in primary PCI cohort is low. However, it is still associated with higher mortality and morbidity. Small stent diameter and disuse of intracoronary glycoprotein IIb/IIIa inhibitor may be associated with early ST., (© 2017 Wiley Periodicals, Inc.)

Background: Approximately 5 to 7% of patients undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery disease require chronic oral anticoagulation (OAC) on top of aspirin and a P2Y 12 receptor antagonist, mainly due to non-valvular atrial fibrillation (AF). The advent of non-vitamin K antagonist oral anticoagulants (NOACs) increased treatment options, while there is cumulative evidence that dual combination of a NOAC and a P2Y 12 receptor antagonist attenuates risk of bleeding, compared to traditional triple therapy, consisting of a vitamin K antagonist (VKA), aspirin, and a P2Y 12 receptor antagonist, without significantly compromising efficacy., Study Design: Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF, NCT 03362788) is an observational, nationwide study of non-valvular AF patients undergoing PCI, planning to enroll over 1-year period > 500 participants in 25 tertiary and non-tertiary PCI centers in Greece. Key data to be collected pre-discharge include demographics, detailed past medical history, and antithrombotic and concomitant treatment. Patients will be followed up at 1, 6, and 12 months post hospital discharge. Αt each follow-up visit, data on antithrombotic treatment, ischemic, bleeding, and adverse events will be collected. Study's primary endpoint is clinically significant bleeding (Bleeding Academic Research Consortium, BARC ≥ 2) at 12 months, between VKAs and NOACs-treated patients, analyzed using Cox proportional hazards models, by an intention-to-treat principle. An independent endpoint committee will adjudicate all clinical events., Conclusions: This study aims at providing "real-world" information on current antithrombotic treatment patterns and clinical outcome of patients with non-valvular AF undergoing PCI.

Aims: The HEAT-PPCI trial compared bivalirudin and unfractionated heparin in patients undergoing primary percutaneous coronary intervention (PPCI). The aim of this study was to report pre-specified, secondary analyses comparing the effects of P2Y12 inhibiting agents on platelet reactivity and clinical events., Methods and Results: All patients received preprocedural oral antiplatelet therapy. During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For cases performed during working hours, multiple electrode aggregometry (MEA) was used to assess ADP-induced platelet aggregation at the end of the index procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all patients. Multiple logistic regression was used to adjust for differences in baseline characteristics. With MEA data from 469 patients, prasugrel therapy resulted in significantly greater suppression of ADP-induced platelet aggregation at 40 U (23, 78) (median; interquartile range [IQR]) when compared against ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In the entire study population (N=1,803), prasugrel therapy was associated with significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123; 7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval (CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel (13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31. Patients treated with clopidogrel had more high-risk features and clopidogrel use was more common as an alternative to prasugrel. After adjustment, there were no significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53)., Conclusions: In HEAT-PPCI, patients who received prasugrel (rather than clopidogrel or ticagrelor) had significantly greater suppression of ADP-induced platelet aggregation at the end of the procedure. After adjustment for differences in baseline characteristics, there were no significant differences in ischaemic or bleeding outcomes among the antiplatelet therapies.

Background: The intracoronary high-thrombus burden during the primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI) can lead to poor outcomes. Monocytes have been described to play an important role in thrombotic disorders., Objectives: This study aimed to investigate the relationship between admission monocyte count and angiographic intracoronary thrombus burden in patients receiving primary percutaneous coronary intervention (PPCI)., Methods: A total of 273 patients with acute STEMI who underwent PPCI were enrolled. The patients were divided into two groups according to the thrombolysis in myocardial infarction (TIMI) thrombus grade: low-thrombus burden group with a grade of 0-2 and high-thrombus burden group with a grade of 3-4. The monocyte count and other laboratory parameters were measured on admission before PPCI. P-value < 0.05 was considered significant., Results: There were 95 patients (34.8%) in the high-thrombus burden group, and 178 patients (65.2%) in the low-thrombus burden group. Patients with high-thrombus burden had significantly higher admission monocyte count (0.61 ± 0.29×109/L vs. 0.53 ± 0.24×109/L, p = 0.021). In multivariate analysis, monocyte count was the independent predictor of angiographic high-thrombus burden (odds ratio 3.107, 95% confidence interval [CI] 1.199-7.052, p = 0.020). For the prediction of angiographic high-thrombus burden, admission monocyte count at a cut-off value of 0.48×109/L yielded 0.59 ROC-AUC (71.9% sensitivity, 46.9% specificity)., Conclusions: Monocyte count on admission was an independent clinical predictor of high-thrombus burden in patients with STEMI undergoing PPCI. Our findings suggest that admission monocyte count may be available for early risk stratification of high-thrombus burden in acute STEMI patients and might allow the optimization of antithrombotic therapy to improve the outcomes of PPCI.

Objective: ABO antigens are highly abundant in many human cell types, including platelets, vascular endothelium, and red blood cells. The presence of a thrombus is associated with adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). We reviewed the relationship between ABO blood groups and thrombus burden in patients with STEMI., Patients and Methods: We carried out a retrospective study of 396 patients with STEMI who did not have an ABO blood group or thrombus burden. The ABO blood type of all participants was determined. First, angiographic characteristics ranging from a nonexistent thrombus to total occlusion were defined as grades 0, 1, 2, 3, 4, and 5, respectively, using the thrombolysis in myocardial infarction (TIMI) scoring system. After wiring and/or small balloon dilation, the patients were split into two groups according to the TIMI grade: large thrombus burden (LTB) (TIMI 4, n=66) and small thrombus burden (STB) (TIMI 0-3, n=330)., Results: The prevalence rates of ABO blood and Rh types were similar between the groups (P>0.05). Moreover, no relationship was found between thrombus burden and the ABO blood group. The ABO blood group was not an independent predictor of large thrombus burden., Conclusion: The present study showed that although previous studies have reported a relationship between the ABO blood type and thrombus burden in the STEMI population, we found no such relationship in our study.

Background: Inhibition of platelet aggregation can reduce the rate of vascular events in patients with coronary artery disease, carotid artery stenosis and symptomatic peripheral arterial disease. The choice of platelet inhibitors in monotherapy and combination therapy as well as the duration of dual platelet inhibition depend on the clinical situation and individual patient characteristics., Goal: The present review summarizes the latest data from clinical trials and recommendations regarding platelet inhibition in coronary, cerebral and peripheral arterial disease., Data: A large number of randomized trials on platelet inhibition in different clinical situations have been performed, allowing evidence-based recommendations on the choice of drugs and duration of treatment. Moreover, new guidelines of European professional societies on platelet inhibition in patients with coronary, cerebral and peripheral arterial disease have been recently published., Conclusion: Based on latest randomized trials and major society guidelines, a number of recommendations on platelet inhibition in stable coronary artery disease, after stent implantation, after acute coronary syndromes and in cerebral and peripheral arterial disease can be made.

The GP IIb/IIIa inhibitors (GPIs) rapidly provide therapeutic levels of platelet aggregation inhibition and serve as adjunct pharmacotherapy to oral P2Y12 inhibitors that exhibit a significant delay in onset of action for patients with Acute Coronary Syndrome (ACS). Intracoronary (IC) administration of the high dose bolus (HDB) tirofiban has not been extensively studied. Compared to intravenous delivery, IC administration can lead to higher local drug concentration and, therefore, provide instantaneous disruption of platelet aggregation in the culprit vessel. This report describes the successful resolution of thrombus using IC HDB tirofiban in 7 high-risk coronary interventions with complications such as recurrent thrombosis and cardiogenic shock in ACS patients. This report represents the first case series of IC HDB tirofiban performed in North America and suggests that IC HDB tirofiban may represent an effective and safe strategy to achieve rapid thrombus resolution in ACS patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The circulating zymogen form of Factor VII activating protease (FSAP) can be activated by histones and nucleosomes in vivo. These cell-death-associated nuclear factors are also actively extruded into the extracellular space by neutrophils through a process called neutrophil extracellular trap (NET) formation (NETosis). NETs are thought to be involved in host defense, inflammation as well as thrombosis. We have investigated the bidirectional interactions of FSAP and NETs. Phorbol ester-mediated NET formation was marginally stimulated by FSAP. Plasma-derived FSAP as well as exogenous FSAP bound to NETs. There was co-localization of FSAP and NETs in coronary thrombi from patients with acute myocardial infarction. Contrary to our expectations no activation of pro-FSAP by NETs was evident. However, after disintegration of NETs with DNase, a robust activation of pro-FSAP, due to release of histones from nucleosomes, was detected. The released histones were in turn degraded by FSAP. Histone cytotoxicity towards endothelial cells was neutralized by FSAP more potently than by activated protein C (APC). One more consequence of histone degradation was a decrease in nucleosome release from apoptotic neutrophils. Taken together, NETs bind to FSAP, but do not activate pro-FSAP unless histones are released from NETs by DNAse. This activation of FSAP is likely to be important in diminishing the cytotoxic effect of histones, thus limiting the damaging effect of NETosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Acute Coronary Syndrome (ACS) patients, despite treatment with Dual Anti- Platelet Therapy (DAPT), have up to 10% risk of recurrent Major Adverse Cardiac Events (MACE) in the short term., Methods: Here we review studies using more potent antithrombotic agent combinations to reduce this risk, namely Triple Therapy (TT) with the addition of an oral anticoagulant, PAR-1 antagonist, or cilostazol to DAPT (mainly aspirin and clopidogrel), and discuss the limitations of trials to date., Results: Generally speaking, TT leads to an increase in bleeding. Vorapaxar showed a signal for reducing ischaemic events, but increased intracranial haemorrhage 3-fold in the subacute phase of ACS, although remains an option for secondary prevention beyond the immediate subacute phase, particularly if prasugrel or ticagrelor are not available. Non-Vitamin K Oral Anticoagulants (NOACs) all increased bleeding, with only modest reduction in MACE noted with low dose rivaroxaban. Rivaroxaban can be considered combined with aspirin and clopidogrel in ACS patients at high ischaemic and low bleeding risk, without prior stroke/TIA. The combination of P2Y12 inhibitor and NOAC, without aspirin, looks promising. DAPT may be replaced, not by TT, but by dual therapy comprising a NOAC with a P2Y12 inhibitor., Conclusion: More potent antithrombotic regimens increase bleeding and should only be considered on an individual basis, after careful risk stratification. Accurate risk stratification of ACS patients, for both ischaemic and bleeding risk, is essential to allow individualised treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objectives: High platelet reactivity (HPR) was studied in patients presenting with ST-segment elevation myocardial infarction (STEMI) due to stent thrombosis (ST) undergoing immediate percutaneous coronary intervention (PCI)., Background: HPR on P2Y 12 inhibitors (HPR-ADP) is frequently observed in stable patients who have experienced ST. The HPR rates in patients presenting with ST for immediate PCI are unknown., Methods: Consecutive patients presenting with definite ST were included in a multicenter ST registry. Platelet reactivity was measured before immediate PCI with the VerifyNow P2Y 12 or Aspirin assay., Results: Platelet reactivity was measured in 129 ST patients presenting with STEMI undergoing immediate PCI. HPR-ADP was observed in 76% of the patients, and HPR on aspirin (HPR-AA) was observed in 13% of the patients. HPR rates were similar in patients who were on maintenance P2Y 12 inhibitor or aspirin since stent placement versus those without these medications. In addition, HPR-ADP was similar in patients loaded with a P2Y 12 inhibitor shortly before immediate PCI versus those who were not. In contrast, HPR-AA trended to be lower in patients loaded with aspirin as compared with those not loaded., Conclusions: Approximately 3 out of 4 ST patients with STEMI undergoing immediate PCI had HPR-ADP, and 13% had HPR-AA. Whether patients were on maintenance antiplatelet therapy while developing ST or loaded with P2Y 12 inhibitors shortly before undergoing immediate PCI had no influence on the HPR rates. This raises concerns that the majority of patients with ST have suboptimal platelet inhibition undergoing immediate PCI., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The alarmin family member myeloid-related protein (MRP)-14 (S100A9), which has been identified by platelet transcriptional profiling as an acute myocardial infarction gene, regulates vascular inflammation and thrombosis. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. The aim of this study was to elucidate pathophysiological roles of MRP-8/14 in acute coronary syndrome (ACS)., Methods and Results: In 38 consecutive ACS patients, the MRP-8/14 level in coronary artery blood obtained at thrombus aspiration was higher in 23 patients, in whom aspirated thrombus was confirmed, compared to the 15 patients, in whom it was absent [4.86 (1.95, 8.29) vs 2.94 (1.31, 4.44), P=0.017]. The MRP-8/14 level was correlated with myeloperoxidase (MPO) level (R 2 =0.52), but not with soluble P-selectin level (R 2 =0.0002) in the coronary artery blood. Immunohistochemistry of the aspirated thrombus exhibited that expression of MRP8/14 was co-localized with leukocytes positive for activated Mac-1. Finally, in cultured human umbilical vein endothelial cells, MRP-8/14 increased tissue factor expression., Conclusions: Our findings indicate that MRP-8/14 concentration increases in coronary artery blood in association with thrombus formation in ACS, co-localizes with leukocytes, and is associated with leukocyte activation. MRP-8/14 is positioned as a unique biomarker at the interface of inflammation and thrombosis in ACS., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

The patient population with the need for oral anticoagulation to reduce stroke risk associated with atrial fibrillation (AF) and dual antiplatelet therapy to prevent stent thrombosis and myocardial infarction after percutaneous coronary intervention is increasing. However, patients treated with a triple therapy consisting of oral anticoagulation, aspirin, and a P2Y12 inhibitor have been demonstrated to be at high bleeding risk. The best combination of these agents and the duration of the different therapies are still uncertain. Recently, data on the safety of combinations including nonvitamin K antagonists have been published and evidence for the feasibility of a dual therapy is increasing. This review aims to provide insights to the pathophysiology of thrombus formation in AF versus coronary artery disease, summarize available data on postprocedural treatment strategies, and report current guidelines for AF patients after percutaneous coronary intervention. Furthermore, the role of stent type selection and tools to evaluate as well as strategies to reduce the individual bleeding risk will be discussed.

Heavy exertion as a trigger of cardiac events has been known since antiquity as it was already described in 492 BC in the famous Athens Marathon. Myocardial infarction occurring after physical exertion accounts for about 4% of myocardial infarctions. It is more common in men and younger patients. It usually occurs during intense efforts and especially in inactive people with multiple risk factors. It would be more severe with more frequent Q waves of necrosis on the victims' electrocardiograms, with greater troponin release and a more raised GRACE score. Atherosclerotic plaque rupture is at the center of its pathophysiology, this event is responsible of a thrombus formation occluding the coronary artery. The hemodynamic stress imposed on the often-atheromatous coronary arteries during exercise, favor the plaque rupture and the occurrence of myocardial infarctions. To these hemodynamic constraints, are added biochemical and rheological modifications, which favor the formation of an intra-coronary thrombus. The occurrence of acute coronary events during heavy exertion in patients who are often untrained must not make us forget about the benefit of regular exercise on both the life quality and morbimortality levels., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Platelets play a key role in the pathophysiology of coronary artery disease and acute coronary syndromes. Our understanding of platelet function in thrombus formation has increased considerably, resulting in the development of clinically effective treatment strategies and identification of new targets. An underappreciated platelet function is their contribution toward acute and chronic inflammatory processes including atherogenesis. In this review, we discuss the role of platelets in atherosclerosis and thrombosis, platelet function testing, and the pharmacology of currently available antiplatelet drugs.

Introduction: Stent thrombosis (ST) is a rare but catastrophic complication of percutaneous coronary intervention, leading to poor prognosis. Endothelin-1 (ET-1) plays an important role in endothelial dysfunction and thrombogenesis. However, the impact of big ET-1 level on ST in patients with coronary stenting is unknown. We aimed to evaluate big ET-1 level as a potential predictor of ST in patients undergoing percutaneous coronary intervention., Materials and Methods: From January 2013 to December 2013, 8106 consecutive patients underwent successful coronary stent implantation and were prospectively enrolled in this study. Patients were stratified into three groups based on plasma big ET-1 level at admission., Results: The incidence of definite and probable ST at 2years postoperatively was 0.84%; ST incidence was lowest in the low big ET-1 group (0.56%), highest in the high big ET-1 group (1.48%), and intermediate in the medium big ET-1 group (0.74%, log-rank p=0.001). Compared with the low big ET-1 group, the multivariate-adjusted hazard ratio (HR) for ST in the high big ET-1 group was 2.06 (95% confidence interval (CI) 1.14-3.73, p=0.017). In subgroup analyses, high big ET-1 level was independently associated with ST in patients with acute coronary syndrome (HR 2.29, 95% CI 1.03-5.06, p=0.041), but not in those with stable coronary artery disease (p=0.331), and tended to be associated with older age., Conclusions: Plasma big ET-1 level is a valuable independent predictor of ST in patients with coronary stents, especially in the acute coronary syndrome population., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The role of erythrocytes in thrombus formation has been often neglected, but some studies have highlighted their active role in thrombotic events. Free-haemoglobin (Hb) has shown to induce oxidative-stress damage. Herein we have investigated the coordinated changes in heme-related proteins in patients with acute-coronary-syndromes (ACS), their association to ongoing thrombosis and their impact on patients' prognosis. The serum proteome of STEMI-patients (N=27) within the first 6h after event-onset and 3d after were compared to controls (N=60). Changes in heme-metabolism were characterized in a second STEMI-group by a dual proteomic approach analyzing in-vivo aspirated coronary thrombi at PCI (N=24) and the associated peripheral-blood changes (N=10). A third STEMI-group (N=132) was studied to analyze the impact of the observed changes in prognosis at 6-months-follow-up. The haptoglobin/hemopexin(Hpg/Hpx)-scavenging-system revealed a time-dependent response after STEMI with an early increase in Hpg circulating levels in the acute phase (P=0.01) and a late increase in Hpx levels 3d after (P=0.045). Beta-Hb content in coronary thrombi was directly correlated with systemic beta-Hb and Hpg (R=0.804,P=0.0029; R=0.859,P=0.0007) levels. The presence of a fully-occlusive thrombus was associated to higher circulating levels of beta-Hb (P=0.03) and unbound-Hpg (P=0.03). ELISA validation demonstrated a decreased survival rate at 6-months follow-up in STEMI-patients with lower Hpg plasma levels at admission (P=0.027). Our results show active Hb-release form erythrocytes in ACS. This release is followed by a systemic early increase in Hpg levels and a late increase in Hpx levels that can co-ordinately help to prevent systemic pro-oxidative effects. The Hb-scavenging ability of haptoglobin is related to patients' prognosis.

Type-2 Diabetes Mellitus [T2DM] is associated with increased platelet reactivity and hypo-response to antiplatelet drugs. Ticagrelor, with its faster and more potent antiplatelet effects, was shown to reduce adverse events more than clopidogrel in the overall CAD patient population of PLATO trial, but the benefits did not reach statistical significance in the T2DM subgroup. To better understand these findings, we compared the antithrombotic effects of ticagrelor versus with clopidogrel in T2DM patients with cardiovascular disease. In a randomized, 2 treatment-sequence, crossover-design, T2DM patients (n=20, 57±8 years, 60 % male) received a loading-dose [LD] plus one week of daily-therapy [DT] of clopidogrel or ticagrelor. Treatment effects were assessed by measuring thrombus formation (Badimon Chamber) and platelet aggregation (Multiple Electrode Aggregometry (MEA) Analyzer and VerifyNow®) at 2- and 6-hour post-LD and on Day-7 of DT, in comparison with pre-treatment baseline. After 2 weeks of washout, patients switched to the second treatment under identical testing conditions. Ticagrelor significantly reduced thrombus formation versus baseline at 2- and 6-hour post-LD and Day-7 of DT (33 %, 40 % and 31 %, respectively, p<0.01 for all) whereas thrombus reductions with clopidogrel were much lower and significant only at 6-hour post-LD (16 %, 20 % and 17 %, respectively). Antithrombotic effect of ticagrelor at 6-hour was significantly stronger than clopidogrel (p<0.05). Platelet aggregation (MEA and VerifyNow®) was inhibited by both treatments but effects of ticagrelor were significantly stronger at each time-point. Ticagrelor exhibits a faster and more potent antithrombotic effect than clopidogrel in T2DM patients with cardiovascular disease, supporting its use in this population.

Antiplatelet therapy with P2Y12-receptor inhibitors has become the cornerstone of medical treatment in patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI). With over 100 million prescriptions filled since its approval, clopidogrel is the most widely used P2Y12-receptor inhibitor. Dual antiplatelet therapy with clopidogrel plus aspirin has been associated with a lower rate of major cardiovascular events in patients after PCI than aspirin monotherapy. However, an alarmingly high number of clopidogrel-treated patients experience adverse thrombotic events. Insufficient P2Y12-inhibition or high on-treatment platelet reactivity to adenosine diphosphate has stimulated the increased use of more potent P2Y12 inhibitors: prasugrel (a third generation thienopyridine) and ticagrelor (a cyclopentyl-triazolo-pyrimidine). However, more potent platelet inhibition and low on-treatment platelet reactivity has resulted in increased major bleeding and higher costs. These limitations have suggested the need for an individualized antiplatelet approach in order to decrease thrombotic events and minimize bleeding. This model of personalized medicine integrates a patient's demographic and biological data (pharmacodynamic, genomic, epigenomic, transcriptomic, and metabolic information) to target therapy in order to maximize efficacy while minimizing bleeding and costs. This review discusses the role of diagnostic tools such as platelet function and pharmacogenomic testing to personalize antiplatelet therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)