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Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03; P =0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26; P =0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

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.

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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.

Background: Standard administration of newer oral P2Y 12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention. We aimed to investigate the effects of cangrelor, tirofiban, and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary percutaneous coronary intervention. Methods: The FABOLUS-FASTER trial (Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over Prasugrel: A Multicenter Randomized Open-Label Trial in Patients with ST-Elevation Myocardial Infarction Referred for Primary Percutaneous Intervention) is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y 12 -naive patients with ST-segment–elevation myocardial infarction were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40) (both administered as bolus and 2-hour infusion followed by 60 mg of prasugrel), or 60-mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 subrandomization to chewed (n=21) or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (noninferiority of cangrelor compared with tirofiban using a noninferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel, and superiority of chewed prasugrel as compared with integral prasugrel, each with α=0.016 for the primary end point, which was 30-minute IPA at light transmittance aggregometry in response to 20 μmol/L adenosine diphosphate. Results: At 30 minutes, cangrelor did not satisfy noninferiority compared with tirofiban, which yielded superior IPA over cangrelor (95.0±8.9 versus 34.1±22.5; P P P =0.47), despite yielding higher prasugrel active metabolite concentration (ng/mL; 62.3±82.6 versus 17.1±43.5; P =0.016). Conclusions: Cangrelor provided inferior IPA compared with tirofiban; both treatments yielded greater IPA compared with chewed prasugrel, which led to higher active metabolite concentration but not greater IPA compared with integral prasugrel. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02978040; URL: https://www.clinicaltrialsregister.eu ; EudraCT 2017-001065-24.

BACKGROUND Determining severity of mitral stenosis (MS) by planimetry of mitral valve orifice area (MVA) has been a challenging issue in clinical practice, especially for less experienced cardiologists. Mitral leaflet separation (MLS) has shown a good correlation with MVA measurements. However, it has never been validated against multiplane 3DTEE planimetry (MVA3D ). We aimed to evaluate the accuracy of MLS index (MLSI2D ) in predicting MS severity. METHODS We prospectively enrolled 144 patients with MS who underwent clinically indicated 2DTTE and 3DTEE. MLSI2D was yield by averaging the maximal leaflet tip distance in diastole, in parasternal long-axis and apical four-chamber views. MVA3D was used as the reference method. RESULTS MLSI2D showed an excellent discriminatory ability between different grades of MS (P

Background We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with followup completed. Findings Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3.81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4.37%) participants in the control group (rate ratio 0.87 [95% CI 0. 75-1. 01]; p=0.073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0.93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2.04% vs 2.12%; rate ratio 0.97 [95% CI 0. 78-1. 20]; p=0.77). Interpretation Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Copright (C) 2018 Elsevier Ltd. All rights reserved. European Clinical Research Institute; Biosensors International; AstraZeneca; Medicines Company; Canada Research Chairs Programme

The superiority of vascular closure devices (VCDs) over manual compression in terms of femoral access complications is debated [(1)][1], and whether their use can narrow the gap in outcomes between radial and femoral access remains unclear [(2,3)][2]. In the MATRIX (Minimizing Adverse Haemorrhagic

Pericardial effusion has various underlying etiologies, and clinicians should identify those that require targeted therapy. Pericardial effusion can be drained either with needle aspiration or surgical procedures. In the following article, we opted to report the results of our 8-year experience of surgical pericardial drainage on 235 consecutive patients. We retrospectively analyzed the medical records of 235 consecutive patients with pericardial effusion and/or tamponade who were submitted to surgical drainage (subxiphoid or left anterolateral pericardiostomy) between the years 2005 and 2013. We aimed to assess the etiology of pericardial effusion, total intra- and post-procedure drainage, length of in-hospital stay, effectiveness of surgical procedures, and related in-hospital mortality. We identified 235 patients, 161 (68.51 %) with severe, 63 (26.80 %) with moderate, and 11 (4.68 %) with mild pericardial effusion. Cardiac tamponade was diagnosed in 91 (38.72 %). The most common established etiologies were idiopathic, uremic, and malignant effusion, respectively. Higher total drained volume was more common in pericardial effusions of malignant etiology than idiopathic (mean difference = 272.02, p = 0.005) or iatrogenic (mean difference = 1096.80, p = 0.001). Mean length of post-procedure drainage was 4.6 days. Intra-operative mortality was 0 % and post-operative was 0.8 % (n = 2). Assessing the data, we concluded that surgical pericardial drainage is a safe and effective method for management of adults with pericardial effusion.