Potent inhibition of thrombin with a monoclonal antibody against tissue factor (Sunol-cH36): results of the PROXIMATE-TIMI 27 trial.

Abstract:

AIMS:Exposure of tissue factor (TF) is a critical proximal step in the pathogenesis of acute coronary syndromes. Sunol-cH36, a chimaeric monoclonal antibody to TF, blocks binding of factor X to the TF:VIIa complex. This report describes the first completed trial of Sunol-cH36 in humans. METHODS AND RESULTS:We assessed the safety and pharmacokinetics of Sunol-cH36 in an open-label, dose-escalating trial among subjects with stable coronary artery disease. The safety analysis included all adverse events with a focus on overt or occult bleeding. Five doses of Sunol-cH36 (0.03, 0.06, 0.08, 0.1, 0.3 mg/kg) were administered as a single intravenous bolus to 26 subjects (three to eight subjects per dose tier). No major bleeding (> or =2 g/dL haemoglobin decline) occurred. Spontaneous minor bleeding was observed with a dose-related pattern. Notably, the majority of spontaneous bleeding episodes were clinically consistent with platelet-mediated bleeding (e.g. gum, tongue) without thrombocytopenia. The median terminal half-life was 72.2 (25th, 75th: 28.4, 72.5) h. CONCLUSION:Sunol-cH36 exhibited dose-dependent anticoagulant effects. We postulate that the mucosal bleeding observed with this potent inhibitor of thrombin generation may reflect antiplatelet effects resulting from networking between the coagulation cascade and platelet pathways that could prove clinically relevant with this novel class of anticoagulants.

journal_name

Eur Heart J

journal_title

European heart journal

authors

Morrow DA,Murphy SA,McCabe CH,Mackman N,Wong HC,Antman EM

doi

10.1093/eurheartj/ehi094

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

682-8

issue

7

eissn

0195-668X

issn

1522-9645

pii

ehi094

journal_volume

26

pub_type

临床试验,杂志文章,多中心研究
  • Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: a retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database.

    abstract:AIMS:Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between ...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究

    doi:10.1093/eurheartj/ehv301

    authors: Fadini GP,Avogaro A,Degli Esposti L,Russo P,Saragoni S,Buda S,Rosano G,Pecorelli S,Pani L,OsMed Health-DB Network.

    更新日期:2015-09-21 00:00:00

  • Stent thrombosis and restenosis: what have we learned and where are we going? The Andreas Grüntzig Lecture ESC 2014.

    abstract::Modern-day stenting procedures leverage advances in pharmacotherapy and device innovation. Patients treated with contemporary antiplatelet agents, peri-procedural antithrombin therapy and new-generation drug-eluting stents (DES) have excellent outcomes over the short to medium term. Indeed, coupled with the reducing c...

    journal_title:European heart journal

    pub_type: 杂志文章,评审

    doi:10.1093/eurheartj/ehv511

    authors: Byrne RA,Joner M,Kastrati A

    更新日期:2015-12-14 00:00:00

  • Acute rise of circulating vascular endothelial growth factor-A in patients with coronary artery disease following cardiothoracic surgery.

    abstract:AIMS:Vascular endothelial growth factor-A (VEGF-A) is an angiogenic and vasoprotective molecule whose expression is modulated by hypoxia and inflammatory mediators. Here we have tested the hypothesis that plasma levels of VEGF-A are influenced by pre-existing coronary artery disease and by changes in circulating interl...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1053/euhj.2001.3034

    authors: Cotton JM,Mathur A,Hong Y,Brown AS,Martin JF,Erusalimsky JD

    更新日期:2002-06-01 00:00:00

  • Progress in the diagnosis of unstable angina and perspectives for treatment.

    abstract::Unstable angina is a high-risk phase of coronary heart disease defined by clinical symptoms. Electrocardiographic findings are heterogeneous and creatine kinase is only rarely elevated. However, troponin T and troponin I are found in about 30-40% of patients with angina at rest disclosing minor myocardial cell injury....

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:

    authors: Hamm CW

    更新日期:1998-11-01 00:00:00

  • Clopidogrel pre-treatment in stable angina: for all patients > 6 h before elective coronary angiography or only for angiographically selected patients a few minutes before PCI? A randomized multicentre trial PRAGUE-8.

    abstract:AIMS:To compare two different clopidogrel regimens on the outcomes of patients undergoing elective coronary angiography (CAG)+/-ad hoc percutaneous coronary intervention (PCI). METHODS AND RESULTS:Open-trial randomized 1028 patients with stable angina to group A ('non-selective'-clopidogrel 600 mg > 6 h before CAG; n ...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1093/eurheartj/ehn169

    authors: Widimsky P,Motovská Z,Simek S,Kala P,Pudil R,Holm F,Petr R,Bílková D,Skalická H,Kuchynka P,Poloczek M,Miklík R,Maly M,Aschermann M,PRAGUE-8 Trial Investigators.

    更新日期:2008-06-01 00:00:00

  • Comparison of the Framingham risk function-based coronary chart with risk function from an Italian population study.

    abstract:AIMS:The aim is to compare the coronary risk chart published by the European Task Force for Prevention of Coronary Heart Disease and produced using a Framingham risk function, with a risk function derived from an Italian population study. METHODS AND RESULTS:Coronary risk function in this study was the result of longi...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1053/euhj.1999.1864

    authors: Menotti A,Puddu PE,Lanti M

    更新日期:2000-03-01 00:00:00

  • Anti-ischaemic intervention with verapamil in patients recovering from acute myocardial infarction.

    abstract::The present review discusses the prognostic significance of post-infarction angina pectoris, and the significance of post-infarction intervention with verapamil on the prevalence of post-infarction ischaemia and prognosis. Angina pectoris during the first month after acute myocardial infarction (AMI) was found to be a...

    journal_title:European heart journal

    pub_type: 杂志文章,评审

    doi:10.1093/eurheartj/16.suppl_h.13

    authors: Jespersen CM

    更新日期:1995-08-01 00:00:00

  • Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts.

    abstract:AIMS:Growth differentiation factor 11 and/or its homologue growth differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and vascular ageing in mice. We investigated whether GDF11/8 associates with cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans. METHODS AND RESULTS:W...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究

    doi:10.1093/eurheartj/ehv385

    authors: Olson KA,Beatty AL,Heidecker B,Regan MC,Brody EN,Foreman T,Kato S,Mehler RE,Singer BS,Hveem K,Dalen H,Sterling DG,Lawn RM,Schiller NB,Williams SA,Whooley MA,Ganz P

    更新日期:2015-12-21 00:00:00

  • Identification of post acute myocardial infarction patients with potential benefit from prophylactic treatment with amiodarone. A substudy of EMIAT (the European Myocardial Infarct Amiodarone Trial).

    abstract:AIMS:To perform a retrospective analysis of subgroups of patients enrolled into the European Myocardial Infarct Amiodarone Trial (EMIAT) in order to identify patients who might benefit from prophylactic amiodarone treatment and patients in whom amiodarone might be harmful. METHODS:Baseline characteristics of the 1486 ...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1053/euhj.1997.0823

    authors: Janse MJ,Malik M,Camm AJ,Julian DG,Frangin GA,Schwartz PJ

    更新日期:1998-01-01 00:00:00

  • Decreased no-reflow in patients with anterior myocardial infarction and pre-infarction angina.

    abstract:AIMS:Pre-infarction angina is associated with better outcome after myocardial infarction. The aim of this study was to assess whether pre-infarction angina is associated with decreased no-reflow after coronary recanalization. METHODS AND RESULTS:Twenty-three patients underwent intracoronary myocardial contrast echocar...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1053/euhj.1999.1714

    authors: Karila-Cohen D,Czitrom D,Brochet E,Faraggi M,Seknadji P,Himbert D,Juliard JM,Assayag P,Steg PG

    更新日期:1999-12-01 00:00:00

  • Discrepancy between angiography and intravascular ultrasound when analysing small coronary arteries.

    abstract:AIMS:A small reference diameter may be the consequence of high plaque burden and diffuse disease. The reference vessel diameter in small coronary arteries may vary according to the method of measurement used. We endeavoured to confirm the difference between data from examinations conducted using angiography with that r...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1053/euhj.2001.2730

    authors: Briguori C,Tobis J,Nishida T,Vaghetti M,Albiero R,Di Mario C,Colombo A

    更新日期:2002-02-01 00:00:00

  • Exercise-induced right ventricular dysfunction is associated with ventricular arrhythmias in endurance athletes.

    abstract:AIMS:Intense exercise places disproportionate strain on the right ventricle (RV) which may promote pro-arrhythmic remodelling in some athletes. RV exercise imaging may enable early identification of athletes at risk of arrhythmias. METHODS AND RESULTS:Exercise imaging was performed in 17 athletes with RV ventricular a...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehv202

    authors: La Gerche A,Claessen G,Dymarkowski S,Voigt JU,De Buck F,Vanhees L,Droogne W,Van Cleemput J,Claus P,Heidbuchel H

    更新日期:2015-08-07 00:00:00

  • In-hospital mortality of patients with atrial arrhythmias: insights from the German-wide Helios hospital network of 161 502 patients and 34 025 arrhythmia-related procedures.

    abstract:Aims:Atrial fibrillation (AFib) and atrial flutter (AFlut) are common arrhythmias with increased use of invasive procedures. A steady re-evaluation of relevant safety endpoints is recommended and both quality management and pay-for-performance programs are evolving. Therefore, the aims of this study were (i) to investi...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究

    doi:10.1093/eurheartj/ehy528

    authors: König S,Ueberham L,Schuler E,Wiedemann M,Reithmann C,Seyfarth M,Sause A,Tebbenjohanns J,Schade A,Shin DI,Staudt A,Zacharzowsky U,Andrié R,Wetzel U,Neuser H,Wunderlich C,Kuhlen R,Tijssen JGP,Hindricks G,Bollmann A

    更新日期:2018-11-21 00:00:00

  • Maternal MTHFR 677C>T is a risk factor for congenital heart defects: effect modification by periconceptional folate supplementation.

    abstract:AIMS:Periconceptional folate supplementation prevents neural tube defects and possibly congenital heart defects (CHD) as well. The search for candidate genes involved in the folate metabolism includes the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism. We studied the association between MTHFR 677C > ...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehi815

    authors: van Beynum IM,Kapusta L,den Heijer M,Vermeulen SH,Kouwenberg M,Daniëls O,Blom HJ

    更新日期:2006-04-01 00:00:00

  • Stress echo applications beyond coronary artery disease.

    abstract::Stress echocardiography is an established method for the diagnosis and prognostic stratification of coronary artery disease. In the last few years, the tremendous technological and conceptual versatility of this technique has been increasingly applied in challenging diagnostic fields. Today, in the echocardiography la...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/eht350

    authors: Picano E,Pellikka PA

    更新日期:2014-04-01 00:00:00

  • Dose-related effects of ACE inhibition in man: quinapril in patients with moderate congestive heart failure. The Study Group on Neurohormonal Regulation in Congestive Heart Failure: Lausanne, Switzerland; Berlin, Düsseldorf, Munich, Germany.

    abstract::Early treatment with ACE inhibitors of even moderate heart failure is clinically beneficial, even though haemodynamic measurements cannot adequately quantitate such improvement. Neurohumoral assessment is, however, supposed to be more accurate. In 55 patients with moderate heart failure (ejection fraction < or = 35%),...

    journal_title:European heart journal

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1093/eurheartj/15.suppl_d.113

    authors: Nussberger J,Fleck E,Bahrmann H,Delius W,Schultheiss HP,Brunner HR

    更新日期:1994-12-01 00:00:00

  • Myocardial hydatid cyst ruptured into the pericardium: cross-sectional echocardiographic study and surgical treatment.

    abstract::We describe a patient with a large intramyocardial hydatid cyst lying in the postero-lateral segment of the left ventricle near the atrioventricular groove level which ruptured into the pericardial sac, resulting in cardiac tamponade. Cross-sectional echocardiographic examination from a modified four-chamber apical vi...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/9.7.819

    authors: De Martini M,Nador F,Binda A,Arpesani A,Odero A,Lotto A

    更新日期:1988-07-01 00:00:00

  • Design and current status of ACTION: A Coronary disease Trial Investigating Outcome with Nifedipine GITS. Gastro-Intestinal Therapeutic System.

    abstract:AIMS:To present the design of ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS), an ongoing multicentre clinical outcome trial with nifedipine GITS (Gastro-Intestinal Therapeutic System) in patients with stable angina pectoris. METHODS:At least 6000 patients with optimally treated stable ang...

    journal_title:European heart journal

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:

    authors: Lubsen J,Poole-Wilson PA,Pocock SJ,van Dalen FJ,Baumann J,Kirwan BA,Parker AB

    更新日期:1998-08-01 00:00:00

  • Three-dimensional imaging of the aortic valve and aortic root with computed tomography: new standards in an era of transcatheter valve repair/implantation.

    abstract::Valvular heart disease is a significant, global cause of morbidity and mortality. In the ageing population of industrialized nations, degenerative aortic stenosis has become the most common native valve disorder. Although surgical aortic valve replacement is associated with excellent clinical outcomes, a large number ...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehp260

    authors: Schoenhagen P,Tuzcu EM,Kapadia SR,Desai MY,Svensson LG

    更新日期:2009-09-01 00:00:00

  • Systematic review of thienopyridine discontinuation and its impact upon clinical outcomes.

    abstract::The optimal length of clopidogrel therapy in patients with acute coronary syndromes or in those who have undergone percutaneous coronary intervention (PCI) remains controversial. We therefore sought to determine the risk of both perioperative and premature discontinuation of clopidogrel. PubMed and EMBASE databases we...

    journal_title:European heart journal

    pub_type: 杂志文章,评审

    doi:10.1093/eurheartj/ehr141

    authors: Gaglia MA Jr,Waksman R

    更新日期:2011-10-01 00:00:00

  • Transcoronary gradients of vascular miRNAs and coronary atherosclerotic plaque characteristics.

    abstract:AIMS:Circulating microRNAs (miRs) may reflect pathophysiologically relevant processes in the atherosclerotically diseased coronary arterial wall. Given the unmet medical need to identify patients with an unstable plaque phenotype, we determined the relation of circulating atherosclerosis-regulatory miRs with plaque phe...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehw047

    authors: Leistner DM,Boeckel JN,Reis SM,Thome CE,De Rosa R,Keller T,Palapies L,Fichtlscherer S,Dimmeler S,Zeiher AM

    更新日期:2016-06-07 00:00:00

  • Natural variability of pulmonary haemodynamics.

    abstract::In the interpretation of the effect of a drug or intervention in a single patient, it is desirable to know the spontaneous fluctuations of the variable under study. A few studies have determined pulmonary haemodynamic variability in acute and short-term intervals. It seems reasonable to adopt a confidence limit of 6 m...

    journal_title:European heart journal

    pub_type: 杂志文章,评审

    doi:10.1093/eurheartj/9.suppl_j.19

    authors: Schrijen F,Jezková J

    更新日期:1988-09-01 00:00:00

  • Sinus of Valsalva aneurysm obstructing coronary arterial flow: case report and collective review of the literature.

    abstract::One case of unruptured sinus of Valsalva aneurysm causing left coronary artery compression and lethal myocardial infarction in a 39-year old woman is described. In reviewing the literature, 15 previously published cases of sinus of Valsalva aneurysms disturbing coronary flow were found. It is concluded that the mechan...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/oxfordjournals.eurheartj.a061811

    authors: Brandt J,Jögi P,Lührs C

    更新日期:1985-12-01 00:00:00

  • Predictive value of high sensitivity C-reactive protein in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention.

    abstract:AIMS:To evaluate the predictive value of high sensitivity (hs) C-reactive protein levels on long-term survival in patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI. METHODS AND RESULTS:We conducted a retrospective analysis of 758 STEMI patients (from January 2003 to December 2005), with...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehm338

    authors: Ortolani P,Marzocchi A,Marrozzini C,Palmerini T,Saia F,Taglieri N,Baldazzi F,Silenzi S,Bacchi-Reggiani ML,Guastaroba P,Grilli R,Branzi A

    更新日期:2008-05-01 00:00:00

  • Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium.

    abstract:BACKGROUND:Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multi...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究

    doi:10.1093/eurheartj/ehv419

    authors: Riegger J,Byrne RA,Joner M,Chandraratne S,Gershlick AH,Ten Berg JM,Adriaenssens T,Guagliumi G,Godschalk TC,Neumann FJ,Trenk D,Feldman LJ,Steg PG,Desmet W,Alfonso F,Goodall AH,Wojdyla R,Dudek D,Philippi V,Opinaldo S

    更新日期:2016-05-14 00:00:00

  • Clinical and prognostic profile of patients with infective endocarditis who need urgent surgery.

    abstract:AIMS:Surgery in patients with infective endocarditis (IE) can be elective (upon completion of antibiotic treatment) or urgent (before antibiotic treatment has ended) when the clinical course is unfavourable. However, urgent surgery for left-sided endocarditis is associated with high mortality. The aims of this study we...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/ehl315

    authors: Revilla A,López J,Vilacosta I,Villacorta E,Rollán MJ,Echevarría JR,Carrascal Y,Di Stefano S,Fulquet E,Rodríguez E,Fiz L,San Román JA

    更新日期:2007-01-01 00:00:00

  • Pyrimidine nucleotide metabolism in cardiac hypertrophy.

    abstract::Cardiac hypertrophy was induced in rats either by isoprenaline treatment or by experimental abdominal aortic stenosis. In both models, the UTP content increased in the hypertrophying heart, while the ATP level remained depressed. The rate of net synthesis of uracil nucleotides, estimated by phosphate incorporation int...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/5.suppl_f.155

    authors: Rossi A,Aussedat J,Olivarès J,Ray A,Verdys M

    更新日期:1984-12-01 00:00:00

  • What is the role of the coronary circulation in congestive heart failure?

    abstract::Manifestations of congestive heart failure are frequently observed in patients with coronary disease. However, they may be predominant in patients who have sustained prior myocardial infarction, in whom left ventricular aneurysm or papillary muscle dysfunction may induce left ventricular dysfunction. A small group of ...

    journal_title:European heart journal

    pub_type: 杂志文章

    doi:10.1093/eurheartj/4.suppl_a.131

    authors: Bertrand ME,Lablanche JM,Thieuleux FA,Tilmant PY

    更新日期:1983-01-01 00:00:00

  • Sustained benefit at 10-14 years follow-up after thrombolytic therapy in myocardial infarction.

    abstract:AIMS:To investigate whether the benefit of thrombolytic therapy was sustained beyond the first decade. We report the 10-14 year outcome of 533 patients who were randomized to treatment with intracoronary streptokinase or to conventional therapy during the years 1980-1985. METHODS AND RESULTS:Details of survival and ca...

    journal_title:European heart journal

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1053/euhj.1998.1443

    authors: Maas AC,van Domburg RT,Deckers JW,Vermeer F,Remme WJ,Kamp O,Manger Cats V,Simoons ML

    更新日期:1999-06-01 00:00:00

  • Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I.

    abstract:BACKGROUND:The CONSENSUS trial was the first study to show prognostic improvement by an ACE inhibitor. Patients in NYHA class IV heart failure were treated with enalapril or placebo. After study completion (average 183 days) all patients were offered open-label enalapril therapy. This paper reports on the survival at t...

    journal_title:European heart journal

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1053/euhj.1998.1098

    authors: Swedberg K,Kjekshus J,Snapinn S

    更新日期:1999-01-01 00:00:00