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Background: In some randomized clinical trials, transradial access (TRA) compared with transfemoral access (TFA) was associated with lower mortality in patients with coronary artery disease undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter randomized clinical trials and whether these associations are modified by patient or procedural characteristics. Methods: We performed an individual patient data meta-analysis of multicenter randomized clinical trials comparing TRA with TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention. The primary outcome was all-cause mortality and the co–primary outcome was major bleeding at 30 days. The primary analysis was conducted by 1-stage mixed-effects models on the basis of the intention-to-treat cohort. The effect of access site on mortality and major bleeding was assessed further by multivariable analysis. The relationship among access site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. Results: A total of 21 600 patients (10 775 TRA, 10 825 TFA) from 7 randomized clinical trials were included. The median age was 63.9 years, 31.9% were women, 95% presented with acute coronary syndrome, and 75.2% underwent percutaneous coronary intervention. All-cause mortality (1.6% versus 2.1%; hazard ratio, 0.77 [95% CI, 0.63–0.95]; P =0.012) and major bleeding (1.5% versus 2.7%; odds ratio, 0.55 [95% CI, 0.45–0.67]; P P interaction =0.003), indicating that the benefit of TRA was substantial in patients with moderate or severe anemia, whereas it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding, respectively. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention and ancillary mechanisms are required to fully explain the causal association. Conclusions: TRA is associated with lower all-cause mortality and major bleeding at 30 days compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit. Registration: URL: https://www.crd.york.ac.uk/prospero ; Unique identifier: CRD42018109664.

The assessment of vascular complexity in the lower limbs provides relevant information about peripheral artery occlusive diseases (PAOD), thus fostering improvements both in therapeutic decisions and prognostic estimation. The current clinical practice consists of visually inspecting and evaluating cine-angiograms of the interested region, which is largely operator-dependent. We present here an automatic method for segmenting the vessel tree and compute a quantitative measure, in terms of fractal dimension (FD), of the vascular complexity. The proposed workflow consists of three main steps: (i) conversion of the cine-angiographies to single static images with a broader field of view, (ii) automatic segmentation of the vascular trees, and (iii) calculation and assessment of FD as complexity index. In particular, this work defines (1) a method to reduce the inter-observer variability in judging vascular complexity in cine-angiography images from patients affected by peripheral artery occlusive disease (PAOD), and (2) the use of Fractal Dimension as a metric of shape complexity of vascular tree. The inter-class correlation coefficient (ICC) is computed as inter-observer agreement metric and to account for possible systematic error, that depends on the experience of the raters. The automatic segmentation of vascular tree achieved an Area Under the Curve mean value of $$0.77~\pm ~0.07$$ 0.77 ± 0.07 , with a min-max range of $$0.57-0.87$$ 0.57 - 0.87 . Absolute operator agreement was higher over the segmented image ($$ICC=0.96$$ I C C = 0.96 ) compared to the video ($$ICC=0.76$$ I C C = 0.76 ) and the a broader field of view image ($$ICC=0.92$$ I C C = 0.92 ). Fractal Dimension computed on both manual segmented images (ground truths) and automatically showed a good correlation with the clinical score (0.85 and 0.75, respectively). Experimental analyses suggest that extracting the vascular tree from cine-angiography can substantially improve the reliability of visual assessment of vascular complexity in PAOD. Results also reveal the effectiveness of FD in evaluating complex vascular tree structures.

Figli del paradosso dell'integrazione (Wrench, Rea e Ouali, 1992), per gli studenti con background migratorio la scuola è il principale elemento costitutivo degli oriz-zonti di attesa (Jedlowski, 2017). Nonostante miglioramenti, i dati (MIUR, 2019) indicano che questi studenti hanno maggiori probabilità di fare esperienza del fe-nomeno di tracking. Dall'analisi di focus group condotti in alcune scuole seconda-rie di primo grado a Napoli, si configura la presenza del paradosso delle aspirazioni (Salikutluk, 2013). Se, da un lato, gli approcci dell'ottimismo degli immigrati e delle opportunità bloccate sembrano spiegare alte aspirazioni, dall'altro, adottando la teoria degli altri significativi, insegnanti e gruppo dei pari sembrano giocare un ruo-lo ambiguo. In particolare, parrebbero essere le forme di esclusione più o meno in-tenzionali generate dalle istituzioni scolastiche (Serpieri e Grimaldi, 2013) a riverbe-rare con più forza sulle aspirazioni, prefigurando pericolose profezie che si auto-avverano (Ravecca, 2009).

BACKGROUND The radial artery is recommended by international guidelines as the default vascular access in patients with acute coronary syndromes (ACS) managed invasively. However, crossover from radial to femoral access is required in 4-10% of cases and has been associated with worse outcomes. No standardised algorithm exists to predict the risk of radial crossover. AIMS We sought to derive and externally validate a risk score to predict radial crossover in patients with ACS managed invasively. METHODS The derivation cohort consisted of 4,197 patients with ACS undergoing invasive management via the randomly allocated radial access from the MATRIX trial. Using logistic regression, we selected predictors of radial crossover and developed a numerical risk score. External validation was accomplished among 3,451 and 491 ACS patients managed invasively and randomised to radial access from the RIVAL and RIFLE-STEACS trials, respectively. RESULTS The MATRIX score (age, height, smoking, renal failure, prior coronary artery bypass grafting, ST-segment elevation myocardial infarction, Killip class, radial expertise) showed a c-index for radial crossover of 0.71 (95% CI: 0.67-0.75) in the derivation cohort. Discrimination ability was modest in the RIVAL (c-index: 0.64; 95% CI: 0.59-0.67) and RIFLE-STEACS (c-index: 0.66; 95% CI: 0.57-0.75) cohorts. A cut-off of ≥41 points was selected to identify patients at high risk of radial crossover. CONCLUSIONS The MATRIX score is a simple eight-item risk score which provides a standardised tool for the prediction of radial crossover among patients with ACS managed invasively. This tool can assist operators in anticipating and better addressing difficulties related to transradial procedures, potentially improving outcomes.

Aims Complex percutaneous coronary intervention (PCI) patients have greater risk of peri-procedural complications, with potential to be associated with poor short-term and late prognosis. Cangrelor is an intravenous P2Y12 receptor inhibitor characterized by rapid onset and offset effect of platelet inhibition which reduced the risk of thrombotic complications. Cangrelor use is currently approved in patients naïve from oral P2Y12 inhibitors with chronic (CCS) or acute coronary syndrome (ACS) undergoing PCI with a IIb recommendation by European guidelines. Yet, the process of switching from cangrelor to oral P2Y12 inhibitor remains uncertain. Methods and Results POMPEII study (NCT04790032) is a prospective registry conducted at Federico II University of Naples enrolling all patients undergoing PCI and receiving cangrelor administration. Pharmacodynamic (PD) assessments were performed at baseline, at 30 minutes, 3 hours and 4-6 hours after cangrelor initiation with 3 assays: 1) the gold standard light transmittance aggregometry (LTA) (20- and 5-µM adenosine diphosphate [ADP] stimuli); 2) VerifyNow P2Y12-test; 3) Multiplate electrode aggregometry (MEA), ADP-test. We enrolled 41 patients undergoing elective complex PCI. All patients were P2Y12 inhibitor naïve and received aspirin, unfractionated heparin, and cangrelor (30-µg/kg bolus followed by 4-µg/kg/min infusion for 2 hours) prior to the start of PCI per standard of care. All patients showed low P2Y12 reactivity at 30 minutes during cangrelor infusion with a mean inhibition of platelet aggregation (IPA, %) of 55.7±18.0% at LTA 20-µM ADP test (34% with IPA ≤50%, 19.5% with IPA≥70%, 4.9% with IPA ≥80% and none IPA ≥90%). High residual platelet reactivity (HRPR) was observed in 1 case (2.4%) as shown by LTA (both 20- and 5-µM ADP stimuli) but not confirmed by VerifyNow and MEA. HRPR was observed in 55% at at 3h and 22.5% at 4-6h at LTA 20-µM and consistently with other assays. All patients with HRPR after cangrelor stop had received clopidogrel as switching drug, while no HRPR was observed in the 4 patients switching to ticagrelor. Conclusions Cangrelor showed to be effective and safe in patients undergoing complex PCI at high thrombotic risk. The switch from cangrelor to clopidogrel could expose patients to a variable period of on-treatment HRPR with inadequate platelet inhibition probably due to the fast offset of cangrelor effect and delay of oral drug effect, while the use of ticagrelor soon after cangrelor start might be ideal to cover the gap. This might be of relevance in such a delicate clinical setting.

Background In the setting of coronary care unit (CCU), early detection of pneumonia is of para-mount important to prevent severe complications. This study was designed aiming to evaluate the diagnostic accuracy of lung ultrasound (LUS) in detection of pneumonia and compared with chest x-ray (CXR). Method We enrolled 110 consecutive patients admitted to CCU of Federico II University Hospital. Each patient underwent CXR and bedside LUS on admission. The final diagnosis (pneumonia vs no-pneumonia) was established by another clinician reviewing clinical and laboratory data independent of LUS results and possibly prescribing chest contrast-enhanced CT (n=34). Results Mean age was 70 ± 11 years old, 68% males. Pneumonia was clinically diagnosis in 26 (23%) patients. LUS was positive for pneumonia in 24 patients (sensitivity 92% specificity 81%). Chest radiography was positive in 9 patients (sensitivity 43% specificity 95%). Using CT scan as referee LUS exhibit 92% of sensibility and a specificity of 96%. In ROC curve analysis diagnostic accuracy of CXR and LUS for diagnosis of pneumonia was 0.86 (95% CI 0.77-0.94), higher than CXR 0.68 (95% CI 0.55-0.84), p Conclusion Based on the findings of the present study, accuracy of LUS in detection of pneumonia was significantly higher than chest x-ray, with comparable sensibility to CT scan.

The transposon theory of aging hypothesizes the activation of transposable elements (TEs) in somatic tissues with age, leading to a shortening of the lifespan. It is thought that TE activation in aging produces an increase in DNA double-strand breaks, contributing to genome instability and promoting the activation of inflammatory responses. To investigate how TE regulation changes in somatic tissues during aging, we analyzed the expression of some TEs, as well as a source of small RNAs that specifically silence the analyzed TEs; the Drosophila cluster named flamenco. We found significant variations in the expression levels of all the analyzed TEs during aging, with a trend toward reduction in middle-aged adults and reactivation in older individuals that suggests dynamic regulation during the lifespan.

Aim Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting. Methods The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up. Conclusion The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S.

Introduction and objectives Patients who are vulnerable to hemodynamic or electrical disorders (VP) are often excluded from clinical trials and data on the optimal access-site or antithrombotic treatment are limited. We assessed outcomes of transradial vs transfemoral access and bivalirudin vs unfractionated heparin (UFH) in VP with acute coronary syndrome undergoing invasive management. Methods The MATRIX trial randomized 8404 patients to radial or femoral access and 7213 patients to bivalirudin or UFH. Among them, 934 (11.1%) were deemed VP due to advanced Killip class (n = 808), cardiac arrest (n = 168), or both (n = 42). The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACE: death, myocardial infarction, or stroke) and net adverse clinical events (NACE: MACE or major bleeding). Results MACE and NACE were similarly reduced with radial vs femoral access in VP and non-VP. Transradial access was also associated with consistent relative benefits in all-cause and cardiovascular mortality or Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding with greater absolute benefits in VP. The effects of bivalirudin vs UFH on MACE and NACE were consistent in VP and non-VP. Bivalirudin was associated with lower all-cause and cardiovascular mortality in VP but not in non-VP, with borderline interaction testing. Bivalirudin reduced bleeding in both VP and non-VP with a larger absolute benefit in VP. Conclusions In acute coronary syndrome patients undergoing invasive management, the effects of randomized treatments were consistent in VP and non-VP, but absolute risk reduction with radial access and bivalirudin were greater in VP, with a 5- to 10-fold lower number needed to treat for benefits. Trial registry number: NCT01433627.

Resumen Introduccion y objetivos A menudo se excluye de los ensayos clinicos a los pacientes hemodinamica o electricamente vulnerables, por lo que escasea la informacion sobre el acceso vascular y el tratamiento antitrombotico optimos. En este trabajo se estudia la evolucion de los pacientes vulnerables con sindrome coronario agudo tratados invasivamente segun el acceso fuera radial o femoral y el tratamiento fuera con bivalirudina o con heparina no fraccionada (HNF). Metodos El estudio MATRIX aleatorizo a 8.404 pacientes a acceso radial o femoral y a 7.213 pacientes a bivalirudina o a HNF. Se considero vulnerables a 934 pacientes (11,1%) debido a clase Killip avanzada (808), parada cardiaca (168) o ambas a la vez (42). El objetivo primario compuesto a 30 dias fueron los eventos cardiovasculares y cerebrovasculares mayores (MACE: muerte, infarto de miocardio e ictus) y los eventos clinicos adversos netos (NACE: MACE o hemorragia grave). Resultados El acceso radial, comparado con el femoral, redujo los MACE y NACE de modo similar en pacientes vulnerables y no vulnerables. El acceso radial se asocio con un claro beneficio relativo en la mortalidad total y cardiovascular y las hemorragias BARC 3 o 5, con mayor beneficio absoluto en los pacientes vulnerables. Los efectos de la bivalirudina comparada con la HNF en MACE y NACE concuerdan entre pacientes vulnerables y no vulnerables. La bivalirudina se asocio con menores mortalidad cardiovascular y por todas las causas en pacientes vulnerables, pero no en los no vulnerables, con test de interaccion en el limite. La bivalirudina redujo las hemorragias en ambos grupos de pacientes, con un beneficio absoluto mayor en el caso de los pacientes vulnerables. Conclusiones En pacientes con sindrome coronario agudo sometidos a tratamiento invasivo, los efectos de los tratamientos aleatorizados fueron concordantes entre los pacientes vulnerables y los no vulnerables, pero la reduccion del riesgo absoluto del acceso radial y bivalirudina fue mayor en los vulnerables, con una reduccion de 5 a 10 veces en el numero de pacientes que es necesario tratar. Numero de registro: NCT01433627.

Background: Elderly status is steadily increasing among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent thrombotic complications in patients with ACS. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. The aim of this study is to evaluate the pharmacodynamic and pharmacokinetic profile of a lower dose of ticagrelor (60 mg twice daily) among elderly patients during the early phase of ACS. Study Design: PLINY THE ELDER (PLatelet INhibition with two different doses of potent P2y12 inhibitors in THE ELDERly population) (NCT04739384) is a prospective, randomized, open-label, crossover trial to evaluate the non-inferiority of a lower dose of ticagrelor (60 mg twice daily) compared with a standard dose (90 mg twice daily) among elderly patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 50 patients, aged 75 years or more, with indication to potent P2Y12 receptor inhibitors will be randomized within 3 days from PCI for the index ACS. Patients with indication to oral anticoagulant therapy, treatment with glycoprotein IIb/IIIa inhibitors, or active bleeding will be excluded. The primary endpoint is platelet reactivity determined by P2Y12 reaction units (PRU) (VerifyNow, Accumetrics, San Diego, CA, USA) after treatment with ticagrelor 60 or 90 mg twice daily for 14 days. Secondary endpoints will include other pharmacodynamic tests of ADP-induced aggregation (light transmittance aggregometry and multiple electrode aggregometry) and determination of pharmacokinetic profile (plasma levels of ticagrelor and its metabolite AR-C124910XX) by high performance liquid chromatography-tandem mass spectrometry. Conclusions: The PLINY THE ELDER trial will determine whether a lower dose of ticagrelor confers non-inferior platelet inhibition compared with the standard dose in the early phase of ACS among elderly patients undergoing PCI, informing future clinical investigation.

Acetylcholine (ACh) is one the major neurotransmitters in insects, whose role in mediating synaptic interactions between neurons in the central nervous system is well characterized. It also plays largely unexplored regulatory functions in non-neuronal tissues. Here we demonstrate that ACh signaling is involved in the modulation of the innate immune response of Drosophila melanogaster. Knockdown of ACh synthesis or ACh vesicular transport in neurons reduced the activation of drosomycin (drs), a gene encoding an antimicrobial peptide, in adult flies infected with a Gram-positive bacterium. drs transcription was similarly affected in Drosophila α7 nicotinic acetylcholine receptor, nAChRalpha7 (Dα7) mutants, as well as in flies expressing in the nervous system a dominant negative form (Dα7

Germline precursors that can be present in asexual animals have never been characterized in aeolosomatids, minute meiofaunal Annelida usually reproducing by paratomic fission with pygidial budding....

Arrhythmogenic cardiomyopathy (ACM) is a genetically determined heart muscle disorder characterized by fibro-fatty replacement of myocardium which may affect the right ventricle (‘dominant right’ variant), the left ventricle (‘dominant left’ variant) or both (‘biventricular disease’ variant). Despite of ACM is one of the main causes of sudden cardiac death (SCD) in young people and athletes as well, the diagnosis of this complex clinical entity still remains a challenge. We report on a case of a 29 years old non-athletic woman with family history of SCD and a long-standing personal history of palpitations leading to frequent accesses to the Accident & Emergency Department. Her echocardiogram was normal while twelve leads ECG revealed negative T waves in the right precordial leads (V1–V3) and post-excitation epsilon waves. ECG Holter monitoring recorded frequent (up to 17 000 in 24 h) polymorphic premature ventricular contractions (PVCs) seldom organized in couplets or triplets. She was followed-up in our clinic and started on Propanolol 40 mg bid with slight relief of symptoms and reduction of PVCs. Cardiac magnetic resonance (CMR) showed regional dyskinesia of both ventricles and RV dilatation. Moreover, tissue characterization findings revealed the presence of diffuse subepicardial late gadolinium enhancement (LGE) of the LV. Genetic analysis was performed and a variant of uncertain significance (VUS) in Desmoplakin was identified. Non sustained monomorphic ventricular tachycardia was induced during electrophysiologic study by programmed ventricular stimulation. In light of these results, we diagnosed biventricular ACM and, after carefully discussion with the patient, a subcutaneous implantable cardioverter defibrillator (ICD) was implanted. The present case should be a persisting reminder that must be considered more than just a single diagnostic tool when dealing with arrhythmic presentations especially in young patients and the importance of contrast CMR along with genetic testing in order to aid clinicians in the demanding selection of the best candidates for ICD implantation.

Dual antiplatelet therapy (DAPT) is the gold standard for the antithrombotic management of patients with an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Implementation of intensified or prolonged DAPT regimens has proven to lower the risk of ischemic events but at the expense of increased bleeding. Importantly, bleeding is a predictor of poor prognosis. Risk stratification and selection of tailored antiplatelet strategies to maximize the net clinical benefit in individual patients with ACS or undergoing PCI is therefore potentially beneficial. Recently, novel approaches including DAPT de-escalation or escalation have been proposed as possible alternatives to standard DAPT. These strategies, which are generally based on patient’s risk profile, genetics, and/or platelet function have been proposed to offer more tailored treatments in patients with ACS or PCI, with the ultimate goal of providing adequate ischemic protection while mitigating the risk of bleeding. This review summarizes the available evidence on DAPT de-escalation or escalation (both guided and unguided) and discusses the practical implications of these strategies in the contemporary management of patients with ACS and/or undergoing PCI.

Improvement in life expectancy of patients suffering from oncohematologic disorders has turned cancer from an acute into a chronic condition, making the management of comorbidities problematic, especially when it comes to both acute and chronic cardiovascular diseases. Treatment-related adverse events and drug–drug interactions often influence the therapeutic approach of patients with active malignancies and cardiovascular disease. Furthermore, tumor cells and platelets maintain a complex crosstalk that on one hand enhances tumor dissemination and on the other hand induces hemostasis abnormalities. Hence, clinicians should move carefully in the intricate land mines established by patients with active cancer under antithrombotic therapy. To date, there is no consensus on the antithrombotic treatment of patients with cardiovascular diseases and concomitant malignancies. The aim of this review is to collect the available scientific evidence, including the latest clinical trials and guidelines, in order to provide guidance on the management of antithrombotic treatment (both antiplatelet and anticoagulant therapy) in cancer patients with either pre-existent or new-onset coronary artery disease. Randomized-controlled trials on antithrombotic treatment in oncologic populations, which by far have thus far been excluded, have to be promoted to supply recommendations in the oncohematologic setting.

Background The impact of coronary artery disease (CAD) extension/complexity on outcomes and on the comparative benefits/risks of zotarolimus-eluting stent (ZES) versus bare-metal stents (BMS) remains unclear in patients at high risk of bleeding or thrombosis or at low restenosis risk. Methods We performed a post-hoc analysis of the ZEUS trial. The impact of coronary anatomic complexity measured by the SYNTAX score on the differences in outcomes following ZES and BMS was assessed at 1 year. Results The mean SYNTAX score was 16.3 ± 13.1 with a median of 12 (IQR: 7 to 22). We stratified patients according to SYNTAX tertiles (0–8: n = 563; >8–19 n = 532; >19: n = 511), and observed that the higher the score, the correspondingly higher was the rate of the primary endpoint of major adverse cardiovascular events (MACE) and other ischemic events, but not bleeding after adjustment. The superior efficacy of ZES versus BMS for MACE was consistent across SYNTAX tertiles (tertile 1: HR 0.71, 95% CI 0.44–1.13; tertile 2: HR 0.71, 95% CI 0.46–1.09; tertile 3: HR 0.83, 95% CI 0.61–1.10) without significant heterogeneity (p for trend = 0.55). This between-groups difference mainly reflected a reduction in MI and TVR without effect on mortality. There was no significant interaction between the SYNTAX score and allocated stent type with respect to ischemic and bleeding endpoints. Conclusions The SYNTAX score was predictor of major adverse cardiovascular events but not bleeding and ZES provided superior efficacy and safety than BMS across the whole spectrum of CAD complexity. SYNTAX score may be routinely used for the assessment of the ischemic risk (but not bleeding) after PCI and should not guide the decision-making for DES versus BMS in patients undergoing PCI.

Antithrombotic therapy is a major cornerstone in the treatment of acute coronary syndromes (ACS), as thrombus formation upon a plaque rupture or an erosion plays a pivotal role in non-ST-segment elevation as well as ST-segment elevation acute coronary syndromes. Both acute and long-term oral antiplatelet therapies, targeting specific platelet activation pathways, have demonstrated significant short- and long-term benefits. The use of anticoagulants is currently largely confined to the acute setting, except in patients with a clear indication for long-term treatment, including atrial fibrillation or the presence of intraventricular thrombi. Despite the benefit of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction, fibrinolytic therapy continues to play an important role throughout the world. In this chapter, the fibrinolytic, antiplatelet, and anticoagulant agents used in the management of acute coronary syndrome patients are discussed.

Antithrombotic therapy is a critical component of the management of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Rapid and profound inhibition of platelet reactivity has been shown to mitigate the ischemic risks and improve myocardial salvage. High residual platelet reactivity (HRPR) has been reported up to 4 or 6 h after loading dose of prasugrel or ticagrelor; therefore, multiple alternative strategies, including crushed or chewed oral tables or intravenous agents, have been investigated to provide a more rapid and sustained inhibition of platelet function and bridge the initial treatment gap. The FABOLUS FASTER is the first investigator-initiated, multicentre, open-label, prospective, randomized study to directly compare the pharmacodynamics effects of cangrelor, tirofiban, chewed or integer prasugrel. This study will add new insights in the management of antiplatelet therapy in patients with STEMI undergoing primary PCI and might be hypothesis-generating for future clinical trials in this field. The trial is registered on clinicaltrials.gov NCT02978040, and EudraCT 2017-001065-24.

Aims After percutaneous coronary intervention (PCI) with second-generation drug-eluting stent (DES), whether short dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 receptor inhibitor confers benefits compared with prolonged DAPT is unclear. Methods and results Multiple electronic databases, including PubMed, Scopus, Web of Sciences, Ovid, and ScienceDirect, were searched to identify randomized clinical trials comparing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT after PCI with second-generation DES implantation. The primary and co-primary outcomes of interest were major bleeding and stent thrombosis 1 year after randomization. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fixed-effect and random-effects models. Multiple sensitivity analyses including random-effects models 95% CI adjustment were applied. A sensitivity analysis comparing trials using P2Y12 inhibitor SAPT with those using aspirin SAPT was performed. A total of five randomized clinical trials (32 145 patients) were available. Major bleeding was significantly lower in the patients assigned to short DAPT followed by P2Y12 inhibitor SAPT compared with those assigned to 12-month DAPT (random-effects model: HR 0.63, 95% 0.45–0.86). No significant differences between groups were observed in terms of stent thrombosis (random-effects model: HR 1.19, 95% CI 0.86–1.65) and the secondary endpoints of all-cause death (random-effects model: HR 0.85, 95% CI 0.70–1.03), myocardial infarction (random-effects model: HR 1.05, 95% CI 0.89–1.23), and stroke (random-effects model: HR 1.08, 95% CI 0.68–1.74). Sensitivity analyses showed overall consistent results. By comparing trials testing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT with trials testing ≤3 months of DAPT followed by aspirin SAPT vs. 12-month of DAPT, there was no treatment-by-subgroup interaction for each endpoint. By combining all these trials, regardless of the type of SAPT, short DAPT was associated with lower major bleeding (random-effects model: HR 0.63, 95% CI 0.48–0.83) and no differences in stent thrombosis, all-cause death, myocardial infarction, and stroke were observed between regimens. Conclusion After second-generation DES implantation, 1–3 months of DAPT followed by P2Y12 inhibitor SAPT is associated with lower major bleeding and similar stent thrombosis, all-cause death, myocardial infarction, and stroke compared with prolonged DAPT. Whether P2Y12 inhibitor SAPT is preferable to aspirin SAPT needs further investigation.