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Background: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. Methods: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. Findings: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. Interpretation: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.

Summary Background The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. Methods Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). Findings The PRAISE score showed an AUC of 0·82 (95% CI 0·78–0·85) in the internal validation cohort and 0·92 (0·90–0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70–0·78) in the internal validation cohort and 0·81 (0·76–0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66–0·75) in the internal validation cohort and 0·86 (0·82–0·89) in the external validation cohort for 1-year major bleeding. Interpretation A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. Funding None.

Background: The rate of intracranial haemorrhage after an acute coronary syndrome has been studied in detail in the era of thrombolysis; however, in the contemporary era of percutaneous coronary intervention, most of the data have been derived from clinical trials. With this background, we aim to analyse the incidence, timing, predictors and prognostic impact of post-discharge intracranial haemorrhage in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: We analysed data from the BleeMACS registry (patients discharged for acute coronary syndrome and undergoing percutaneous coronary intervention from Europe, Asia and America, 2003–2014). Analyses were conducted using a competing risk framework. Uni and multivariate predictors of intracranial haemorrhage were assessed using the Fine–Gray proportional hazards regression analysis. The endpoint was 1-year post-discharge intracranial haemorrhage. Results: Of 11,136 patients, 30 presented with intracranial haemorrhage during the first year (0.27%). The median time to intracranial haemorrhage was 150 days (interquartile range 55.7–319.5). The fatality rate of intracranial haemorrhage was very high (30%). After multivariate analysis, only age (subhazard ratio 1.05, 95% confidence interval 1.01–1.07) and prior stroke/transient ischaemic attack (hazard ratio 3.29, 95% confidence interval 1.36–8.00) were independently associated with a higher risk of intracranial haemorrhage. Hypertension showed a trend to associate with higher intracranial haemorrhage rate. The combination of older age (⩾75 years), prior stroke/transient ischaemic attack, and/or hypertension allowed us to identify most of the patients with intracranial haemorrhage (86.7%). The annual rate of intracranial haemorrhage was 0.1% in patients with no risk factors, 0.2% in those with one factor, 0.6% in those with two factors and 1.3% in those with three factors. Conclusion: The incidence of intracranial haemorrhage in the first year after an acute coronary syndrome treated with percutaneous coronary intervention is low. Advanced age, previous stroke/transient ischaemic attack, and hypertension are the main predictors of increased intracranial haemorrhage risk.

BACKGROUND The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Background The use of potent P2Y12 inhibitors (ticagrelor & prasugrel) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions (PCI) is a class I recommendation. We performed a sex-specific analysis comparing the difference in efficacy and safety outcomes between ticagrelor and prasugrel in a real-world ACS population. Methods Data from the multicenter REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) for 4424 ACS patients who underwent PCI and were treated with ticagrelor or prasugrel between 2012 to 2016 were analyzed. Mean follow-up was 17±9 months. Results After propensity score matching, there was no significant difference in the occurrence of primary endpoint of net adverse cardiac events between ticagrelor and prasugrel in men (HR: 0.94; 95% CI: 0.69-1.29; P=0.71), or women (HR: 1.17; 95% CI: 0.63-2.20; P=0.62; P interaction [sex] = 0.40). Similarly, no differences were found in the occurrence of any of the secondary endpoints (MACE, all cause death, re-infarction, stent thrombosis, BARC major bleeding and BARC any bleeding) between the two P2Y12 groups between men and women. Conclusions In this real-world ACS population, no relative difference in efficacy or safety outcomes were found between ticagrelor and prasugrel between sexes.

Introduction and objectives There is little evidence on rates of stent thrombosis (ST) in patients receiving dual antiplatelet therapy (DAPT) with ticagrelor or prasugrel . The aim of this study was to analyze the incidence and predictors of ST after an acute coronary syndrome among patients receiving DAPT with ticagrelor vs prasugrel. Methods We used data from the RENAMI registry (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction), analyzing a total of 4123 acute coronary syndrome patients discharged with DAPT with ticagrelor or prasugrel in 11 centers in 6 European countries. The endpoint was definite ST within the first year. A competitive risk analysis was carried out using a Fine and Gray regression model, with death being the competitive event. Results A total of 2604 patients received DAPT with ticagrelor and 1519 with prasugrel; ST occurred in 41 patients (1.10%), with a similar cumulative incidence between ticagrelor (1.21%) and prasugrel (0.90%). The independent predictors of ST were age (sHR, 1.03; 95% C I, 1.01-1.06), ST segment elevation (sHR, 2.24; 95%CI, 1.22-4.14), previous myocardial infarction (sHR, 2.56; 95%CI, 1.19-5.49), and serum creatinine (sHR, 1.29; 95%CI, 1.08-1.54). Conclusions Stent thrombosis is infrequent in patients receiving DAPT with ticagrelor or prasugrel. The variables associated with an increased risk of ST were advanced age, ST segment elevation, previous myocardial infarction, and serum creatinine.

Resumen Introduccion y objetivos Hay muy poca evidencia sobre las tasas de trombosis del stent (TS) en pacientes que reciben tratamiento antiagregante plaquetario doble (TAPD) con ticagrelor o prasugrel. El objetivo de este estudio es analizar la incidencia y predictores de la TS tras un sindrome coronario agudo en pacientes que reciben TAPD con ticagrelor frente a prasugrel. Metodos Se utilizaron datos del registro RENAMI (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction), y se analizo en total a 4.123 pacientes con sindrome coronario agudo dados de alta con TAPD con ticagrelor o prasugrel en 11 centros de 6 paises europeos. Se considero como evento la TS confirmada en el primer ano. Se realizo un analisis de riesgos competitivos mediante un modelo de regresion de Fine y Gray, siendo la muerte el evento competitivo. Resultados Recibieron TAPD con ticagrelor 2.604 pacientes y con prasugrel, 1.519; 41 pacientes (1,10%) presentaron TS, con incidencias acumuladas similares entre ticagrelor (1,21%) y prasugrel (0,90%). Los predictores independientes de la TS fueron: la edad (sHR = 1,03; IC95%, 1,01-1,06), la elevacion del segmento ST (sHR = 2,24; IC95%, 1,22-4,14), el antecedente de infarto de miocardio (sHR = 2,56; IC95%, 1,19-5,49) y la creatinina serica (sHR = 1,29; IC95%, 1,08-1,54). Conclusiones La TS es infrecuente en pacientes que reciben TAPD con ticagrelor y prasugrel. La edad avanzada, la elevacion del segmento ST, el antecedente de infarto y la creatinina serica son las variables que se asocian con mayor riesgo de TS.

Resumen Introduccion y objetivos La puntuacion PARIS permite una estratificacion combinada de los riesgos isquemico y hemorragico de los pacientes con cardiopatia isquemica tratados con stent coronario y tratamiento antiagregante plaquetario doble (TAPD). Se desconoce su utilidad en pacientes con sindrome coronario agudo (SCA) tratados con ticagrelor o prasugrel. Se investiga este aspecto en un registro internacional. Metodos Estudio retrospectivo multicentrico con participacion voluntaria de 11 centros de 6 paises europeos. Se estudio a 4.310 pacientes con SCA dados de alta en TAPD con ticagrelor o prasugrel. Se definio evento isquemico como trombosis de stent o infarto de miocardio espontaneo, y evento hemorragico segun BARC (Bleeding Academic Research Consortium) tipo 3 o 5. Se calculo la discriminacion y la calibracion para ambas vertientes de la puntuacion PARIS (PARISisquemico y PARIShemorragico). El beneficio neto isquemico-hemorragico se obtuvo mediante la diferencia entre las probabilidades predichas de eventos isquemicos y hemorragicos. Resultados Durante 17,2 ± 8,3 meses, hubo 80 eventos isquemicos (el 1,9% anual) y 66 eventos hemorragicos (el 1,6% anual). PARISisquemico y PARIShemorragico se asociaron con el riesgo de eventos isquemicos (sHR = 1,27; IC95%, 1,16-1,39) y hemorragicos (sHR = 1,14; IC95%, 1,01-1,30) respectivamente. La discriminacion de eventos isquemicos fue discreta (indice C = 0,64) y la de eventos hemorragicos, pobre (indice C = 0,56), con buena calibracion para ambos. El beneficio neto isquemico-hemorragico resulto negativo (mas eventos hemorragicos) en pacientes con alto riesgo hemorragico y positivo (mas eventos isquemicos) en pacientes con alto riesgo isquemico. Conclusiones En pacientes con SCA tratados con TAPD con ticagrelor o prasugrel, la escala PARIS ayuda a establecer un equilibrio apropiado del riesgo isquemico-hemorragico.

Aims The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. Methods and results All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR Conclusion In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Introduction The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. Methods All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3–5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2–5 bleeding, cardiovascular death and stent thrombosis. Results A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p Conclusion In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk–benefit ratio for longer DAPT due to excess of bleedings.

Background The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed to help clinicians at individualizing the optimal dual antiplatelet therapy duration (DAPT) after percutaneous coronary intervention (PCI). Nevertheless, external validation of these RSs it has not yet been performed in ACS (acute coronary syndrome) patients treated with prasugrel or ticagrelor in a real- world scenario. Methods 4424 ACS patients who underwent PCI and survived to hospital discharge, from January 2012 to December 2016 at 12 European centers, were included. PRECISE-DAPT and PARIS bleeding RS, as well as PARIS ischemic RS, were computed, and their performance at predicting major bleeding (MB; BARC type 3 or 5) and ischemic events (MI and stent thrombosis) during follow up was compared. Results After a median follow-up of 14 (interquartile range 12–20.9) months, 83 (1.88%) patients developed MB and 133 (3.0%) suffered an ischemic episode. PRECISE-DAPT performed better than PARIS bleeding RS (c-statistic = 0.653 vs. 0.593; p = .01 for comparison) in predicting MB. The RSs performance for MB prediction remained consistent in STEMI patients (c-statistic = 0.632 vs 0.575) or in those treated with prasugrel (c-statistic = 0.623 vs 0.586). PARIS ischemic RS exhibited superior discrimination in predicting ischemic complications compared to PRECISE-DAPT (c-statistic = 0.604 vs 0.568 p = .05 for comparison). Conclusion Our data provide support to the use of PRECISE-DAPT in MB risk stratification for patients receiving DAPT in form of aspirin and prasugrel or ticagrelor whereas the PARIS ischemic RS has potential to complement the risk prediction with respect to ischemic events.

Introduction: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. Methods: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. Results: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3–5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3–5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3–5 events. Conclusion: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Introduction and objectives For patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), it is unclear whether angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are associated with reduced mortality, particularly with preserved left ventricular ejection fraction (LVEF). The goal of this study was to determine the association between ACEI/ARB and mortality in ACS patients undergoing PCI, with and without reduced LVEF. Methods Data from the BleeMACS registry were used. The endpoint was 1-year all-cause mortality. The prognostic value of ACEI/ARB was tested after weighting by survival-time inverse probability and after adjustment by Cox regression, propensity score, and instrumental variable analysis. Results Among 15 401 ACS patients who underwent PCI, ACEI/ARB were prescribed in 75.2%. There were 569 deaths (3.7%) during the first year after hospital discharge. After multivariable adjustment, ACEI/ARB were associated with lower 1-year mortality, ≤ 40% (HR, 0.62; 95%CI, 0.43-0.90; P = .012). The relative risk reduction of ACEI/ARB in mortality was 46.1% in patients with LVEF ≤ 40%, and 15.7% in patients with LVEF > 40% (P value for treatment-by-LVEF interaction = .008). For patients with LVEF > 40%, ACEI/ARB was associated with lower mortality only in ST-segment elevation myocardial infarction (HR, 0.44; 95%CI, 0.21-0.93; P = .031). Conclusion The benefit of ACEI/ARB in decreasing mortality after an ACS in patients undergoing PCI is concentrated in patients with LVEF ≤ 40%, and in those with LVEF > 40% and ST-segment elevation myocardial infarction. In non–ST-segment elevation-ACS patients with LVEF > 40%, further studies are needed to assess the prognostic impact of ACEI/ARB.

Objectives The aim of this study was to test the hypothesis that more intensive over standard anticoagulation administered during coronary angiography would significantly reduce rates of radial artery occlusion (RAO). Background RAO, although silent, remains a frequent and therefore worrisome complication following transradial coronary angiography. Anticoagulation is effective in reducing RAO, but the optimal heparin dose remains ill defined. Methods In this multicenter, randomized superiority trial, a high dose (100 IU/kg body weight administered in divided doses) and a standard dose (50 IU/kg body weight) of heparin during 5- or 6-F coronary angiography were compared. A total of 3,102 patients were randomized, of whom 1,836 patients not proceeding to percutaneous coronary intervention and without need for arterial access crossover entered the trial. Post-catheterization hemostasis did not follow a rigid protocol. Results A total of 102 early RAOs were found on ultrasonography (incidence 5.6%). In the high-dose heparin group, the rate of RAO was significantly lower compared with the standard-dose heparin group (27 [3.0%] vs. 75 [8.1%]; odds ratio: 0.35; 95% confidence interval: 0.22 to 0.55; p Conclusions High compared with standard heparin dose significantly reduced the rate of RAO in patients undergoing coronary angiography. High-intensity anticoagulation should be considered in transradial diagnostic procedures. (High [100IU/Kg] Versus Standard [50IU/Kg] Heparin Dose for Prevention of Forearm Artery Occlusion; NCT02570243 )

Background: Endothelial function may be improved by ticagrelor through adenosine-mediated mechanisms. We aimed to assess the effect of ticagrelor versus prasugrel on endothelial function in patients with stable coronary artery disease (CAD). Methods: In a prospective, randomized, crossover study, 22 stable CAD patients under prasugrel 10 mg once daily maintenance dose (MD) for at least 3 months were randomized to either ticagrelor 90 mg twice daily or prasugrel 10 mg once daily for 15 days with a direct treatment-crossover for another 15 days. Endothelial function was assessed by peripheral arterial tonometry (EndoPAT 2000 system, Itamar Medical, Caesarea, Israel) at Day 0 (randomization), Day 15, and Day 30. Reactive Hyperemia Index (RHI) was calculated by using an automated software, and endothelial dysfunction (ED) was defined as RHI

Ticagrelor is a P2Y12 receptor antagonist with proven clinical benefit in patients with acute coronary syndrome. Apart from its principal antiplatelet action, pleiotropic effects have been implicated in the clinical profile of ticagrelor, including a potentially beneficial impact on endothelial function. In light of the common presence and prognostic value of endothelial dysfunction in patients with coronary artery disease, several clinical studies have investigated the postulated effect of ticagrelor on endothelial function, yielding conflicting results. Limitations of the relevant studies as well as substantial differences in patient population, study design, and methods may account for these controversial findings. Most of these studies, however, support a beneficial impact of ticagrelor on endothelial function, which seems to be significant in the higher risk patients. In order to elucidate this effect, further research efforts should aim to clarify how quickly does endothelial function respond to ticagrelor, how sustained this response is during the dosing intervals and in the long term, which mechanisms are implicated, and whether this pleiotropic action is clinically significant. Future studies should include larger and diverse populations of patients, assess endothelial function at several time points after treatment initiation, and use multiple methods of endothelial function measurement, while implementing strict methodology. Nevertheless, the extent of the clinical benefit of ticagrelor attributable to actions beyond its potent and consistent antiplatelet effect remains uncertain.

AIMS The aim of this study was to compare the performance of the Tiger-II with Judkins 3.5L/4R catheters in coronary angiography (CAG) via the transradial approach (TRA). METHODS AND RESULTS Consecutive patients undergoing non-urgent CAG via the right TRA were randomised to either the Tiger-II (Terumo) or Judkins (3.5L/4R; Medtronic) 5 Fr catheters; 320 patients in each group were randomised. Catheter or access site change was required in 57 (17.8%) vs. 68 (21.3%) patients allocated to the Tiger-II and Judkins group, respectively (p=0.3). The study's primary endpoint of contrast volume (ml) used until completion of CAG was lower for Tiger-II vs. Judkins group: 66.8 (54.0-82.0) vs. 73.4 (60.0-94.1), p

Purpose: The aim was to evaluate prognostic value of beta-blocker (BB) administration in acute coronary syndromes (ACS) patients in the percutaneous coronary intervention (PCI) era. Methods and Results: The BleeMACS project is a multicenter, observational, retrospective registry enrolling patients with ACS worldwide in 15 hospitals. Patients discharged with BB therapy were compared to those discharged without a BB before and after propensity score with matching. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included in-hospital reinfarction, in-hospital heart failure, 1-year myocardial infarction, 1-year bleeding and 1-year composite of death and recurrent myocardial infarction. After matching, 2935 patients for each group were enrolled. The primary endpoint of 1-year death was significantly lower in the group on BB therapy (4.5 vs 7%, p < 0.05), while only a trend was noted for recurrent acute myocardial infarction (4.5 vs 4.9%, p = 0.54). These results were consistent for patients older than 80 years of age, for ST-elevation myocardial infarction (STEMI) patients, and for those discharged with complete versus incomplete revascularization, but not for non-STEMI/unstable angina patients. Conclusions: BB therapy was related to 1-year lower risk of all-cause mortality, independently from completeness of revascularization, admission diagnosis, age and ejection fraction. Randomized controlled trials for patients treated with PCI for ACS should be performed.

Introduction: Bleeding is an independent risk factor of mortality in patients with acute coronary syndromes (ACS). BleeMACS project focuses on long-term bleeding events after hospital discharge, thus we evaluated gender-related differences in post-discharge bleeding among patients with ACS. Materials and methods: We investigated 13,727 ACS patients treated with percutaneous coronary intervention and discharged on dual antiplatelet therapy (either with clopidogrel or prasugrel/ticagrelor). Endpoint was defined as intracranial bleeding or any other bleeding leading to hospitalization and/or red blood transfusion. Results: Post-discharge bleeding was reported more frequently in females as compared with males (3.7% vs. 2.7%, log-rank P = 0.001). Females (n = 3165, 23%) were older compared to men (69.0 vs. 61.5 years, P < 0.001) and with more comorbidities. Hence, in multivariate analysis female sex was not identified as an independent risk factor of bleeding (HR 1.012, CI 0.805 to 1.274, P = 0.816). Administration of newer antiplatelet agents compared to clopidogrel was associated with over twofold greater bleeding rate in females (7.3% vs. 3.5%, log-rank P = 0.004), but not in males (2.6% vs. 2.7%, log-rank P = 0.887). Differences among females remained significant after propensity score matching (7.2% vs 2.4%, log-rank P = 0.020) and multivariate analysis confirmed that newer antiplatelet agents are independent risk factor for bleeding only in women (HR 2.775, CI 1.613 to 4.774, P < 0.001). Conclusions: Bleeding events occurred more frequently in women, but female sex itself was not independent risk factor. Administration of newer antiplatelet agents was identified as independent risk factor of bleeding after hospital discharge in female gender, but not in male patients.

BACKGROUND AND AIMS We compared the clinical outcome of diabetic versus nondiabetic patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the GReek AntiPlatElet (GRAPE) registry. PATIENTS AND METHODS GRAPE is a prospective observational study, focusing on contemporary antiplatelet use in moderate-risk to high-risk ACS patients receiving PCI. Major adverse cardiovascular events (MACE), (composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium definition) at 1 year of follow-up were analyzed using propensity score adjustment. A subanalysis according to diabetes mellitus (DM) status was performed. RESULTS Out of 2047 registered patients, 469 (22.9%) were diabetic. Complete 1-year follow-up was available in 95.1% of patients. MACE occurred in 12.2 and 7.2% of those patients with and without DM, respectively [adjusted hazard ratio (HR), 95% confidence interval (CI)=1.27 (0.89-1.79), P=0.2]. Observed BARC type ≥3 bleeding risk was not higher in diabetic patients: adjusted HR (95% CI)=1.20 (0.79-1.84). In the subgroup of clopidogrel-treated patients (N=238), MACE rate was significantly higher in diabetic compared with nondiabetic cohort [13.4 vs. 9%, adjusted HR (95% CI)=1.68 (1.07-2.64), P=0.03]. In the subgroup of ticagrelor-treated or prasugrel-treated patients (N=228), MACE rate did not differ significantly between diabetic and nondiabetic patients: 9.6 versus 5%, adjusted HR (95% CI)=1.35 (0.77-2.37), P=0.38. CONCLUSION In 'real-life' ACS undergoing PCI, diabetic patients have higher - although not significantly - MACE rate and no difference in bleeding events. This difference in MACE was significant among clopidogrel-treated patients, whereas when newer antiplatelet agents were used the negative impact of DM on ischemic events was eliminated.

Background: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. Methods and results: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, PConclusion: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

OBJECTIVES The effect of a functioning arteriovenous fistula on cardiac function in kidney transplant recipients has not been thoroughly investigated. MATERIALS AND METHODS We retrospectively evaluated cardiac function in 99 renal transplant recipients using transthoracic echocardiography, with available follow-up at baseline and 2 and 5 years posttransplant. Patients were divided into 2 groups: a control group (n = 47) with no functioning arteriovenous fistula immediately after transplant and an arteriovenous fistula group (n = 52) with a functioning arteriovenous fistula for at least 5 years after transplant. Left ventricular ejection fraction, diastolic thickness of the interventricular septum, and left ventricular end-diastolic diameter were assessed. RESULTS In our study, patients (62.6% men, 7.1% with diabetes, mean age of 55.6 ± 11.5 years), we observed no significant differences with respect to baseline left ventricular ejection fraction and interventricular septum; however, in the arteriovenous fistula group, baseline left ventricular end-diastolic diameter was marginally higher than that shown in the control group (50.6 ± 5.4 vs 48.6 ± 4.4 mm; P = .054). In multivariate analysis, functioning fistula and peripheral arterial disease were negatively associated with left ventricular ejection fraction at 5 years posttransplant, whereas baseline left ventricular ejection fraction had a minimal positive effect: B (95% confidence interval) of -2.186 (-4.312 to -0.061) (P = .044), -5.304 (-9.686 to -0.922) (P = .018), and 0.247 (0.047 to 0.446) (P = .016), respectively. Functioning fistula also emerged as associated with larger left ventricular end-diastolic diameter at 2 and 5 years posttransplant: B (95% confidence interval) of 3.047 (1.470-4.625) (P < .001) and 2.122 (0.406-3.838) (P = .016), respectively. CONCLUSIONS Maintenance of a functioning fistula in kidney transplant recipients may be associated with adverse long-term effects on left ventricular ejection fraction and left ventricular end-diastolic diameter.

Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI). Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population. RENAMI was a retrospective, observational registry including the data and outcomes of consecutive patients with acute coronary syndrome (ACS) who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT) between January 2012 and January 2016. The mean follow-up period was 17 ± 9 months. In total, 11 university hospitals from six European countries participated. After propensity-score matching, there were no substantial differences in the baseline clinical and interventional features. All patients were treated with acetylsalicylic acid plus prasugrel 10 mg once daily or acetylsalicylic acid plus ticagrelor 90 mg twice daily. Mean duration of DAPT was 12.04 ± 3.4 months with prasugrel and 11.90 ± 4.1 months with ticagrelor (p = 0.47). The primary and secondary endpoints were long-term net adverse clinical events (NACE) and major adverse cardiovascular events (MACE), respectively, along with their single components. Subgroup analysis for freedom from NACE and MACE was performed according to length of DAPT and clinical presentation [ST-elevation myocardial infarction (STEMI)-ACS versus non-ST-elevation myocardial infarction (NSTEMI)-ACS]. In total, 4424 patients (2725 ticagrelor, 1699 prasugrel) were enrolled. After propensity-score matching, 1290 patients in each cohort were included in the analysis. At 12 months, the incidence of both NACE and MACE was lower with prasugrel (NACE: 5.3% vs. 8.5% [p = 0.001]; MACE: 5% vs. 8.1% [p = 0.001]) mainly driven by a reduction in recurrent myocardial infarction (MI) (2.4 vs. 4.0%; p = 0.029) and a lower rate of Bleeding Academic Research Consortium (BARC) 3–5 bleeding (1.5 vs. 2.9%; p = 0.011). The benefit of prasugrel was confirmed for patients with NSTEMI and for those discharged with a DAPT regimen of ≤ 12 months. Only a trend in the reduction of NACE and MACE was noted for STEMI or for those treated with longer DAPT. Comparison of these drugs suggested that prasugrel is safer and more efficacious than ticagrelor in combination with aspirin after NSTEMI but not STEMI. No differences were found for events occurring after 12 months. The nonrandomized design of the present research means further studies are required to support these findings.

Resumen Introduccion y objetivos No esta clara la asociacion entre los inhibidores de la enzima de conversion de la angiotensina (IECA) o los antagonistas del receptor de la angiotensina II (ARA-II) y la mortalidad de los pacientes con sindrome coronario agudo (SCA) sometidos a intervencion coronaria percutanea (ICP) con fraccion de eyeccion del ventriculo izquierdo (FEVI) conservada. Nuestro objetivo es determinar dicha asociacion en pacientes con FEVI conservada o reducida. Metodos Se analizaron datos procedentes del registro BleeMACS. El objetivo principal fue la mortalidad a 1 ano. Se aplicaron ponderacion por la probabilidad inversa del tiempo de supervivencia y ajustes por regresion de Cox, puntuacion de propension y variables instrumentales. Resultados De los 15.401 pacientes con SCA sometidos a ICP, se prescribieron IECA/ARA-II al 75,2%. Se produjeron 569 muertes (3,7%) durante el primer ano tras el alta hospitalaria. Despues del ajuste multivariado, los IECA/ARA-II se asociaron con menor mortalidad, pero solo en los pacientes con FEVI ≤ 40% (HR = 0,62; IC95%, 0,43-0,90; p = 0,012). Con los IECA/ARA-II, la reduccion del riesgo relativo de la mortalidad estimada fue del 46,1% en los pacientes con FEVI ≤ 40% y del 15,7% en aquellos con FEVI > 40% (pinteraccion = 0,008). En los pacientes con FEVI > 40%, los IECA/ARA-II se asociaron con menor mortalidad solo por infarto agudo de miocardio con elevacion del segmento ST (HR = 0,44; IC95%, 0,21-0.93; p = 0,031). Conclusiones El beneficio de los IECA/ARA-II en mortalidad tras ICP por SCA se concentra en pacientes con FEVI ≤ 40% y aquellos con FEVI > 40% e infarto agudo de miocardio con elevacion del segmento ST. Se precisan estudios contemporaneos que analicen el impacto de los IECA/ARA-II en pacientes con SCA sin elevacion del segmento ST y FEVI > 40%.

The association between prior stroke/transient ischemic attack (TIA) and clinical outcomes in patients with acute coronary syndrome (ACS) has not been well explored. We evaluated the impact of prior stroke/TIA on this specific patient population. We conducted an international multicenter study including 15 401 patients with ACS from the Bleeding Complications in a Multicenter Registry of Patients Discharged With Diagnosis of Acute Coronary Syndrome registry. They were divided into 2 groups: patients with and without prior stroke/TIA. The primary end point was death at 1-year follow-up. Prior stroke/TIA was associated with higher rate of 1-year death (8.7% vs 3.4%; P < .001). It was an independent predictor of 1-year death even after adjustment for confounding variables (odds ratio, 1.705; 95% confidence interval, 1.046-2.778; P = .032). Besides, patients with prior stroke/TIA had significantly increased 1-year reinfarction (5.6% vs 3.8%, P = .015), in-hospital bleeding (8.7% vs 5.8%, P < .001), and 1-year bleeding (5.2% vs 3.0%, P < .001). No difference of antithrombotic therapies or dual antiplatelet therapy (DAPT) types on outcomes was observed in patients with prior stroke/TIA. Prior stroke/TIA was associated with higher 1-year death for patients with ACS who underwent percutaneous coronary intervention. No benefits or harms were observed with different antithrombotic therapies or DAPT types in these patients.

Background: Ticagrelor may exert pleiotropic actions, beyond platelet inhibition, which are possibly adenosine-mediated. It has been suggested that in patients with coronary artery disease (CAD) ticagrelor may influence endothelial function. Objective: We aimed to assess the possibility of endothelial function deterioration following ticagrelor treatment cessation. Methods: This was a prospective, observational study, in stable CAD patients with prior percutaneous coronary intervention (PCI) for acute coronary syndrome manifested 1 year earlier, under ticagrelor maintenance dose (90 mg bid) and due to discontinue ticagrelor. Endothelial function was assessed by Peripheral Arterial Tonometry (EndoPat 2000 system, Itamar Medical, Caesarea, Israel) immediately after receiving the last tablet of ticagrelor (Day 0) and at Day 2 and Day 5 post-ticagrelor cessation. Reactive hyperaemia index (RHI) was calculated by automated software and endothelial dysfunction (ED) was defined as a RHI

Background Blood transfusions (BTs) may worsen the prognosis of patients affected by acute coronary syndromes (ACS), although few data detail their impact on short-term events according to clinical presentation (ST Segment Elevation Myocardial Infarction, STEMI vs. Non-ST Segment Elevation ACS, NSTE-ACS). Methods Patients undergoing percutaneous coronary intervention (PCI) for ACS, with data on BTs, were selected from the BleeMACS registry. The primary end point was the incidence of myocardial infarction during hospitalization (reAMI), the secondary end-points were 30-day mortality and the combined end-point of 30-day mortality and reAMI. Sensitivity analyses were performed according to clinical presentation (STEMI vs. NSTE-ACS). Results Overall, 13,975 patients were included: mean age was 64.1years, 10,651 (76.2%) were male and 7711 (55.2%) had STEMI. BTs were administered during hospitalization to 465 (3.3%) patients, who were older and presented a more relevant burden of risk factors. The primary end-point of reAMI occurred in 197 (1.4%) patients, of whom 102 (1.1%) with STEMI. After controlling for confounding variables, BTs independently predicted the primary end-point reAMI in patients admitted for STEMI (OR 4.059, 95% CI 2244–7.344) and not in those admitted for NSTE-ACS. Moreover, BTs independently related to 30-day mortality in STEMI and NSTE-ACS patients and to the composite of 30-day mortality and reAMI in STEMI patients. Conclusions In patients undergoing PCI for ACS, BTs increase the risk of reAMI only in those admitted for STEMI, and not in those with NSTE-ACS. These results may help physicians to choose appropriate BT administration according to the admission diagnosis.

Physicians considering prescription of P2Y12-receptor antagonist for long-term (>1 year) protection of patients post-myocardial infarction face the trilemma of selecting between clopidogrel, prasugrel, or ticagrelor. Differential ischemic benefits derived from relevant trials may assist in tailoring treatment, although the different bleeding definitions applied make any meaningful comparison of each agent’s bleeding potential very difficult. Considering the available data and recognizing the significant limitation of observations obtained thus far from subgroup analyses, prasugrel appears to provide higher anti-ischemic protection than clopidogrel. Ticagrelor seems to be an attractive option for patients with renal dysfunction, peripheral arterial disease, or following a brief P2Y12-receptor antagonist interruption, whereas clopidogrel may be advised in the presence of cost and availability issues. As head-to-head comparative trials between P2Y12-receptor antagonists are lacking, selection of a specific agent by the clinician should be made on the basis of critical appraisal of available large clinical datasets.

Essentials The comparative efficacy and safety of antiplatelet agents in ‘real life’ is not clear. We recruited acute coronary syndrome patients receiving percutaneous coronary intervention. At 1-year follow-up, prasugrel offers better anti-ischemic protection than clopidogrel. Prasugrel and ticagrelor are accompanied by more frequent bleeding events. SummaryBackground The comparative efficacy and safety of antiplatelet treatment outside randomized trials is not clear. Objectives To investigate long-term efficacy and safety in ‘real-life’ acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with contemporary use of clopidogrel, prasugrel and ticagrelor. Methods In a prospective, observational, multicenter cohort study, 2047 patients were recruited into the GReek AntiPlatElet (GRAPE) Registry and were followed-up for 1 year for major adverse cardiovascular events (MACE, a composite of death, non-fatal myocardial infarction, urgent revascularization and stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] classification). Results Exposure to clopidogrel, prasugrel and ticagrelor by PCI occurred in 959, 363 and 717 patients, respectively. After adjustment, the rate of MACE (primary outcome endpoint) was lower in prasugrel-treated patients (4.4%) than in clopidogrel-treated patients (10.1%) (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.30–0.91), although not significantly different between ticagrelor (6.8%) and clopidogrel groups (HR, 0.78; 95% CI, 0.54–1.12). Any type of BARC-classified bleeding (secondary outcome endpoint) was more frequent in prasugrel-treated patients (51.2%) than in clopidogrel-treated patients (37.6%) (HR, 1.61; 95% CI, 1.33–1.95) and more frequent in ticagrelor-treated patients (56.9%) than in clopidogrel-treated patients (HR, 1.81; 95% CI, 1.55–2.10). An adjusted comparison between prasugrel and ticagrelor-treated groups did not reveal differences in any outcome measure. After adjustment, the death rate was more reduced by novel agents in comparison with clopidogrel (2.9% vs. 6.2%). Conclusions In ACS/PCI patients, prasugrel offered better anti-ischemic protection than clopidogrel, whereas use of both novel agents is accompanied by more frequent bleeding events.

BACKGROUND Delay in the onset of antiplatelet action occurs in patients with ST-elevation myocardial infarction (STEMI) and is likely due to disturbed absorption. We hypothesized that patients presenting relatively late after the onset of symptoms would have faster antiplatelet action. METHODS AND RESULTS We analyzed patient-level data from 5 studies of 207 P2Y12 receptor antagonist-naive patients with STEMI undergoing primary percutaneous coronary intervention (PCI). All patients had available platelet reactivity (PR) assessment with the VerifyNow assay (in P2Y12 reaction units; PRU) prior to and 2 h after loading. High PR (HPR) was defined as ≥ 208 PRU. Pain-to-antiplatelet loading time independently predicted PR at 2 h after loading: every 1-h increase in pain-to-antiplatelet loading time produced a 7% decrease in PR (P=0.001). Pretreatment PR, body mass index, morphine and novel P2Y12 receptor antagonist also affected PR 2 h after loading. Novel P2Y12 receptor antagonist use and per hour increase in pain-to-antiplatelet loading time were independently associated with lower probability for HPR with an OR (95% CI) of 0.145 (0.095-0.220) and 0.776 (0.689-0.873), P

The aim of this study was to test the hypothesis that more intensive over standard anticoagulation administered during coronary angiography would significantly reduce rates of radial artery occlusion (RAO).RAO, although silent, remains a frequent and therefore worrisome complication following transradial coronary angiography. Anticoagulation is effective in reducing RAO, but the optimal heparin dose remains ill defined.In this multicenter, randomized superiority trial, a high dose (100 IU/kg body weight administered in divided doses) and a standard dose (50 IU/kg body weight) of heparin during 5- or 6-F coronary angiography were compared. A total of 3,102 patients were randomized, of whom 1,836 patients not proceeding to percutaneous coronary intervention and without need for arterial access crossover entered the trial. Post-catheterization hemostasis did not follow a rigid protocol.A total of 102 early RAOs were found on ultrasonography (incidence 5.6%). In the high-dose heparin group, the rate of RAO was significantly lower compared with the standard-dose heparin group (27 [3.0%] vs. 75 [8.1%]; odds ratio: 0.35; 95% confidence interval: 0.22 to 0.55; p 0.001), without compromising safety. The time to achieve hemostasis was similar between groups. To avoid 1 RAO, the number of patients needed to treat in the high-dose heparin group was approximately 20. These results were corroborated by our integrated database, showing an 80% reduction of forearm artery occlusions in high versus low heparin dose patients and our updated meta-analysis of randomized controlled trials demonstrating significant benefit of higher over lower anticoagulation intensity.High compared with standard heparin dose significantly reduced the rate of RAO in patients undergoing coronary angiography. High-intensity anticoagulation should be considered in transradial diagnostic procedures. (High [100IU/Kg] Versus Standard [50IU/Kg] Heparin Dose for Prevention of Forearm Artery Occlusion; NCT02570243).

Radial artery (RA) occlusion (RAO) remains the Achilles heel of transradial coronary procedures. Although of silent nature, RAO is relatively frequent, results in graft shortage for future coronary artery bypass surgery, and may occur even after short-lasting, 5F coronary angiography (CAG). The most frequent predictors of RAO are RA size, body size, female gender, and periprocedural anticoagulation intensity. Methods to detect RAO are variable, of which the Barbeau test and ultrasonography have similar diagnostic accuracy. Data indicate that late RAO recanalization may occur. Meticulous handling of RA and the use of appropriate hemostatic devices and techniques along with sufficient heparin dose appear important measures to reduce RAO rates. Recent contradictory studies indicate that the decreasing incidence of RAO overtime is not as uniform as previously thought. In 2 meta-analyses, the benefit of higher over lower anticoagulation intensity became evident. As “it may all be appropriate anticoagulation” for a simplified approach against RAO, the results of an ongoing trial comparing 100 with 50 IU/kg body weight in transradial CAG are eagerly awaited.

Introduction: The safety and efficacy of prasugrel and ticagrelor in patients with diabetes mellitus presenting with acute coronary syndrome and treated with percutaneous coronary intervention remain to be assessed. Methods: All diabetes patients admitted for acute coronary syndrome and enrolled in the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) were compared before and after propensity score matching. Net adverse cardiovascular events (composite of death, stroke, myocardial infarction and BARC 3–5 bleedings) and major adverse cardiovascular events (composite of death, stroke and myocardial infarction) were the co-primary endpoints. Single components of primary endpoints were secondary endpoints. Results: Among 4424 patients enrolled in RENAMI, 462 and 862 diabetes patients treated with prasugrel and ticagrelor, respectively, were considered. After propensity score matching, 386 patients from each group were selected. At 19±5 months, major adverse cardiovascular events and net adverse cardiovascular events were similar in the prasugrel and ticagrelor groups (5.4% vs. 3.4%, P=0.16 and 6.7% vs. 4.1%, P=0.11, respectively). Ticagrelor was associated with a lower risk of death and BARC 2–5 bleeding when compared to prasugrel (2.8% vs. 0.8%, P=0.031 and 6.0% vs. 2.6%, P=0.02, respectively) and a clear but not significant trend for a reduction of BARC 3–5 bleeding (2.3% vs. 0.8%, P=0.08). There were no significant differences in myocardial infarction recurrence and stent thrombosis. Conclusion: Diabetes patients admitted for acute coronary syndrome seem to benefit equally in terms of major adverse cardiovascular events from ticagrelor or prasugrel use. Ticagrelor was associated with a significant reduction in all-cause death and bleedings, without differences in recurrent ischaemic events, which should be confirmed in dedicated randomised controlled trials.

Ticagrelor and prasugrel are recommended as first line therapy in patients with acute coronary syndromes (ACS). However, patients with anemia are commonly treated with clopidogrel in routine clinical practice. The RENAMI registry (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction) included ACS patients treated with prasugrel or ticagrelor at hospital discharge. The aim of this study was to analyze the prevalence of anemia and characteristics and outcomes of these patients according to anemia status.Consecutive patients with ACS from 11 centers were included. All patients underwent percutaneous coronary intervention (PCI). Anemia was defined as hemoglobin130 g/L in men and120 g/L in women. The incidence of ischemic and bleeding events and all-cause mortality were assessed at one year.From 4424 patients included, 405 (9.2%) fulfilled criteria of anemia. Patients with anemia were significantly older, had a higher prevalence of peripheral artery disease, previous bleeding and renal disfunction and higher bleeding risk (PRECISE-DAPT score ≥ 25: 37.3% vs 18.8%, p 0.001) The incidence of BARC 3/5 bleeding was moderately higher in patients with anemia (5.4% vs 1.5%, p = 0.001). The incidence of stent thrombosis or reinfarction was not significantly different according to anemia status. Anemia was independently associated with mortality (HR 1.73; 95% CI 1.03-2.91, p = 0.022).A not negligible proportion of patients treated with ticagrelor or prasugrel met criteria for anemia. Anemia was an independent predictor of mortality. Despite their higher bleeding risk profile, patients with anemia had an acceptable rate of bleeding.

Introduction and objectives The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry. Methods Retrospective multicenter study with voluntary participation of 11 centers in 6 European countries. We studied 4310 patients with ACS discharged with DAPT with ticagrelor or prasugrel. Ischemic events were defined as stent thrombosis or spontaneous myocardial infarction, and hemorrhagic events as BARC (Bleeding Academic Research Consortium) type 3 or 5 bleeding. Discrimination and calibration were calculated for both PARIS scores (PARIS ischemic and PARIShemorrhagic). The ischemic-hemorrhagic net benefit was obtained by the difference between the predicted probabilities of ischemic and bleeding events. Results During a period of 17.2 ± 8.3 months, there were 80 ischemic events (1.9% per year) and 66 bleeding events (1.6% per year). PARISischemic and PARIShemorrhagic scores were associated with a risk of ischemic events (sHR, 1.27; 95%CI, 1.16-1.39) and bleeding events (sHR, 1.14; 95%CI, 1.01-1.30), respectively. The discrimination for ischemic events was modest (C index = 0.64) and was suboptimal for hemorrhagic events (C index = 0.56), whereas calibration was acceptable for both. The ischemic-hemorrhagic net benefit was negative (more hemorrhagic events) in patients at high hemorrhagic risk, and was positive (more ischemic events) in patients at high ischemic risk. Conclusions In patients with ACS treated with DAPT with ticagrelor or prasugrel, the PARIS model helps to properly evaluate the ischemic-hemorrhagic risk.

Background A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients. Methods We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine–Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). Results The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92–2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001). Conclusion Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients.

Objectives To evaluate “real life” incidence and independent predictors of major bleeding defined in ACS patients treated with PCI and current standard antithrombotic therapy with prasugrel or ticagrelor. Methods and results The RENAMI project is a multicenter retrospective observational registry enrolling 4424 patients with ACS treated with PCI and prasugrel or ticagrelor plus aspirin. Primary endpoint was MACE (major adverse cardiovascular events). Secondary endpoints included each component of MACE, cardiovascular death (CV death), recurrence of ACS (reACS) and stroke. Eighty three (1.8%) patients developed out of hospital major bleedings after 14.1 ± 6.2 months. These patients had higher rates of MACE (14.5% vs 4.4%; p = 0.001) and of all-cause death (11% vs 2.1%; p 75 years (OR 2.00; 95% CI 1.18–3.41; p = 0.010) and female sex (OR 1.66; 95% CI 1.02–2.70; p = 0.041). BARC 3–5 bleeding was independently associated with all-cause mortality (OR 3.46; 95% CI 1.64–7.31; p 0.001). Conclusion In ACS patients treated with PCI and ticagrelor or prasugrel, BARC 3–5 bleedings despite being uncommon negatively impacted on prognosis. Old and female patients are at increased risk, offering clinical indications for tailoring dual antiplatelet therapy.

The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We randomized 20 patients to ticagrelor 180 mg either as 2 integral tablets administered in the supine position (standard administration) or as 2 tablets crushed and dispersed, administered in the semi-upright sitting position. Blood samples were drawn for pharmacokinetic and pharmacodynamic assessment at randomization (0 h) and at 0.5, 1, 2, and 4 h. At 1 h, ticagrelor plasma exposure and area under the plasma concentration–time curve from time zero to 1 h (AUC1) (co-primary endpoints) were higher in the crushed versus integral tablets group (median 586 vs. 70.1 ng/mL and 234 vs. 24.4 ng·h/mL, respectively), with a ratio of adjusted geometric means (95 % confidence interval [CI]) of 12.67 (2.34–68.51) [p = 0.005] and 19.28 (3.51–106.06) [p = 0.002], respectively. Time to maximum plasma concentration was shorter in the crushed versus integral tablets group (median 2 vs. 4 h), with a ratio of adjusted geometric means (95 % CI) of 0.69 (0.49–0.97) [p = 0.035]. Parallel findings were observed with AR-C124910XX (active metabolite). Platelet reactivity (VerifyNow®) at 1 h was lower with crushed versus standard administration with least squares estimates mean difference (95 % CI) of 92 (−158.4 to 26.6) P2Y12 reaction units (p = 0.009). In patients with STEMI undergoing primary PCI, ticagrelor crushed tablets administered in the semi-upright sitting position seems to lead to a faster—compared with standard administration—absorption, with stronger antiplatelet activity within the first hour. Trial registration: ClinicalTrials.gov identifier: NCT02046486.

Background: Major, noncoronary complications are rarely encountered following transradial coronary procedures. Methods and Results: Among 1600 prospectively studied patients with complete follow-up, 7 patients experienced major complications following coronary forearm procedures corresponding to an incidence of 0.44%. We found inadvertent symptomatic intramyocardial contrast medium injection, 2 cases with compartment syndrome of which 1 was managed surgically, exertional hand ischemia due to radial artery occlusion, a large ulnar artery pseudoaneurysm, an ulnar arteriovenous fistula, and 1 critical hand ischemia due to late occlusion of the distal brachial artery. Conclusions: Although infrequent, surveillance for major complications should be encouraged after forearm coronary procedures.

Limited data are available on high platelet reactivity (HPR) rate early post fibrinolysis, while no effective way to overcome it has been proposed. In this context, we aimed to compare ticagrelor versus high dose clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) who exhibit HPR post fibrinolysis. In a prospective, randomized, parallel design, 3-center study, 56 STEMI patients, out of 83 (67.5 %) screened, who presented with HPR (PRU ≥ 208 by VerifyNow) 3–48 h post fibrinolysis and prior to coronary angiography were allocated to ticagrelor 180 mg loading dose (LD)/90 mg bid maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD. Platelet reactivity was assessed at randomization (Hour 0), at Hour 2, Hour 24 and pre-discharge. The primary endpoint of platelet reactivity (in PRU) at Hour 2 was significantly lower for ticagrelor compared to clopidogrel with a least square mean difference (95 % confidence interval) of −141.7 (−173.4 to −109.9), p

Background Incidence of radial artery occclusions (RAO) and ulnar artery occclusions (UAO) in coronary procedures, factors predisposing to forearm arteries occlusion, and the benefit of anticoaggulation vary significantly in existing literature. We sought to determine the incidence of RAO/UAO and the impact of anticoagulation intensity. Methods and Results Meta‐analysis of 112 studies assessing RAO and/or UAO (N=46 631) were included. Overall, there was no difference between crude RAO and UAO rates (5.2%; 95% confidence interval [CI], 4.4–6.0 versus 4.0%; 95% CI, 2.8–5.8; P =0.171). The early occlusion rate (in‐hospital or within 7 days after procedure) was higher than the late occlusion rate. The detection rate of occlusion was higher with vascular ultrasonography compared with clinical evaluation only. Low‐dose heparin was associated with a significantly higher RAO rate compared with high‐dose heparin (7.2%; 95% CI, 5.5–9.4 versus 4.3%; 95% CI, 3.5–5.3; Q=8.81; P =0.003). Early occlusions in low‐dose heparin cohorts mounted at 8.0% (95% CI, 6.1–10.6). The RAO rate was higher after diagnostic angiographies compared with coronary interventions, presumably attributed to the higher intensity of anticoagulation in the latter group. Hemostatic techniques (patent versus nonpatent hemostasis), geography (US versus non‐US cohorts) and sheath size did not impact on vessel patency. Conclusions RAO and UAO occur with similar frequency and in the order of 7% to 8% when evaluated early by vascular ultrasonography following coronary procedures. More‐intensive anticoagulation is protective. Late recanalization occurs in a substantial minority of patients.