Evolving Treatments for Arterial and Venous Thrombosis: Role of the Direct Oral Anticoagulants.

Abstract:

:The direct oral anticoagulants (DOACs) represent a major advance in oral anticoagulant therapy and have replaced the vitamin K antagonists as the preferred treatment for many indications. By simplifying long-term anticoagulant therapy and improving its safety, the DOACs have the potential to reduce the global burden of thrombosis. Postmarketing studies suggest that the favorable results achieved with DOACs in the randomized controlled trials can be readily translated into practice, but highlight the need for appropriate patient, drug and dose selection, and careful follow-up. Leveraging on their success to date, ongoing studies are assessing the utility of DOACs for the prevention of thrombosis in patients with embolic stroke of unknown source, heart failure, coronary artery disease, peripheral artery disease, antiphospholipid syndrome, and cancer. The purpose of this article is to (1) review the pharmacology of the DOACs, (2) describe the advantages of the DOACs over vitamin K antagonists, (3) summarize the experience with the DOACs in established indications, (4) highlight current challenges and limitations, (5) highlight potential new indications; and (6) identify future directions for anticoagulant therapy.

journal_name

Circ Res

journal_title

Circulation research

authors

Chan NC,Eikelboom JW,Weitz JI

doi

10.1161/CIRCRESAHA.116.306925

subject

Has Abstract

pub_date

2016-04-29 00:00:00

pages

1409-24

issue

9

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.116.306925

journal_volume

118

pub_type

杂志文章,评审
  • Erythrocyte Metabolic Reprogramming by Sphingosine 1-Phosphate in Chronic Kidney Disease and Therapies.

    abstract:RATIONALE:Hypoxia promotes renal damage and progression of chronic kidney disease (CKD). The erythrocyte is the only cell type for oxygen (O2) delivery. Sphingosine 1-phosphate (S1P)-a highly enriched biolipid in erythrocytes-is recently reported to be induced under high altitude in normal humans to enhance O2 delivery...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.119.316298

    authors: Xie T,Chen C,Peng Z,Brown BC,Reisz JA,Xu P,Zhou Z,Song A,Zhang Y,Bogdanov MV,Kellems RE,D'Alessandro A,Zhang W,Xia Y

    更新日期:2020-07-17 00:00:00

  • Rho kinase mediates cold-induced constriction of cutaneous arteries: role of alpha2C-adrenoceptor translocation.

    abstract::Cold-induced vasoconstriction in cutaneous blood vessels is mediated in part by increased activity of vascular smooth muscle alpha2-adrenoceptors (VSM alpha2-ARs). In mouse cutaneous arteries, alpha2C-ARs are normally silent at 37 degrees C but mediate cold-induced augmentation of alpha2-AR responsiveness. In transfec...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000128407.45014.58

    authors: Bailey SR,Eid AH,Mitra S,Flavahan S,Flavahan NA

    更新日期:2004-05-28 00:00:00

  • Cardiovascular Disease in Women: Clinical Perspectives.

    abstract::Cardiovascular disease continues to be the leading cause of death among women in the United States, accounting for ≈1 of every 3 female deaths. Sex-specific data focused on cardiovascular disease have been increasing steadily, yet is not routinely collected nor translated into practice. This comprehensive review focus...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.116.307547

    authors: Garcia M,Mulvagh SL,Merz CN,Buring JE,Manson JE

    更新日期:2016-04-15 00:00:00

  • C-Peptide induces vascular smooth muscle cell proliferation: involvement of SRC-kinase, phosphatidylinositol 3-kinase, and extracellular signal-regulated kinase 1/2.

    abstract::Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest a potential causal role of C-peptide in atherogenesis by promoting monocyte and T-lymphocyte recruitment into the vessel wall. The present study examine...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000251231.16993.88

    authors: Walcher D,Babiak C,Poletek P,Rosenkranz S,Bach H,Betz S,Durst R,Grüb M,Hombach V,Strong J,Marx N

    更新日期:2006-11-24 00:00:00

  • Depressed beta-adrenergic receptor- and endothelium-mediated vasodilation in conscious dogs with heart failure.

    abstract::Peripheral vasodilator responsiveness was examined in pacing-induced heart failure (HF) in 11 conscious dogs chronically instrumented for measurement of systemic (total peripheral resistance [TPR]) and local (iliac blood flow) vascular resistance. Dose responses to isoproterenol (ISO), acetylcholine (ACh), and nitrogl...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.73.6.1013

    authors: Kiuchi K,Sato N,Shannon RP,Vatner DE,Morgan K,Vatner SF

    更新日期:1993-12-01 00:00:00

  • Thrombin stimulates smooth muscle cell differentiation from peripheral blood mononuclear cells via protease-activated receptor-1, RhoA, and myocardin.

    abstract:RATIONALE:Smooth muscle precursor cells have previously been reported to reside in bone marrow and in the circulation, but little is currently known regarding the proximate stimuli for smooth muscle cell differentiation of these putative progenitors. OBJECTIVE:Because local thrombin generation occurs as an initial res...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.199984

    authors: Martin K,Weiss S,Metharom P,Schmeckpeper J,Hynes B,O'Sullivan J,Caplice N

    更新日期:2009-07-31 00:00:00

  • Polyploidy in Cardiomyocytes: Roadblock to Heart Regeneration?

    abstract::The hallmark of most cardiac diseases is the progressive loss of cardiomyocytes. In the perinatal period, cardiomyocytes still proliferate, and the heart shows the capacity to regenerate upon injury. In the adult heart, however, the actual rate of cardiomyocyte renewal is too low to efficiently counteract substantial ...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.119.315408

    authors: Derks W,Bergmann O

    更新日期:2020-02-14 00:00:00

  • Unspliced XBP1 Confers VSMC Homeostasis and Prevents Aortic Aneurysm Formation via FoxO4 Interaction.

    abstract:RATIONALE:Although not fully understood, the phenotypic transition of vascular smooth muscle cells exhibits at the early onset of the pathology of aortic aneurysms. Exploring the key regulators that are responsible for maintaining the contractile phenotype of vascular smooth muscle cells (VSMCs) may confer vascular hom...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.311450

    authors: Zhao G,Fu Y,Cai Z,Yu F,Gong Z,Dai R,Hu Y,Zeng L,Xu Q,Kong W

    更新日期:2017-12-08 00:00:00

  • Reduced reperfusion-induced Ins(1,4,5)P3 generation and arrhythmias in hearts expressing constitutively active alpha1B-adrenergic receptors.

    abstract::Reperfusion of globally ischemic rat hearts causes the generation of inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] and the initiation of arrhythmias. These responses are mediated by alpha1-adrenergic receptors (ARs), but the subtype of receptor involved has not been identified. Under normoxic conditions, hearts from tra...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.83.12.1232

    authors: Harrison SN,Autelitano DJ,Wang BH,Milano C,Du XJ,Woodcock EA

    更新日期:1998-12-14 00:00:00

  • Sodium pump inhibition, enhanced calcium influx via sodium-calcium exchange, and positive inotropic response in cultured heart cells.

    abstract::The effects of sodium pump inhibition produced by exposure to the cardiac glycosides, ouabain or dihydroouabain, or by reduction in extracellular potassium to 1.0 mM, on contractile state and sodium-calcium exchange were studied in primary monolayer cultures of chick embryo ventricular cells. Ouabain, 10(-6)M, dihydro...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.56.2.231

    authors: Barry WH,Hasin Y,Smith TW

    更新日期:1985-02-01 00:00:00

  • Selective antagonism of hormone-induced vasoconstriction by synthetic atrial natriuretic factor in the rat microcirculation.

    abstract::Synthetic atrial natriuretic factor (ANF) was either added to suffusate solutions (30 nM) or infused into the jugular vein (0.1 nanomol/min/100 g) of anesthetized rats. Steady-state blood flow was calculated from arteriolar diameter and red blood cell velocity measurements using video microscopy in the intestinal or s...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.61.1.42

    authors: Proctor KG,Bealer SL

    更新日期:1987-07-01 00:00:00

  • Microtubule involvement in translational regulation of fibronectin expression by light chain 3 of microtubule-associated protein 1 in vascular smooth muscle cells.

    abstract::Our previous studies suggested that enhanced fibronectin mRNA translation in ductus arteriosus compared with aortic smooth muscle cells is related to increased expression of light chain 3 (LC3) of microtubule-associated protein 1, which binds an AU-rich element in the 3' untranslated region of fibronectin mRNA. We the...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.83.5.481

    authors: Zhou B,Rabinovitch M

    更新日期:1998-09-07 00:00:00

  • A critical function for Ser-282 in cardiac Myosin binding protein-C phosphorylation and cardiac function.

    abstract:RATIONALE:Cardiac myosin-binding protein-C (cMyBP-C) phosphorylation at Ser-273, Ser-282, and Ser-302 regulates myocardial contractility. In vitro and in vivo experiments suggest the nonequivalence of these sites and the potential importance of Ser-282 phosphorylation in modulating the protein's overall phosphorylation...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.242560

    authors: Sadayappan S,Gulick J,Osinska H,Barefield D,Cuello F,Avkiran M,Lasko VM,Lorenz JN,Maillet M,Martin JL,Brown JH,Bers DM,Molkentin JD,James J,Robbins J

    更新日期:2011-07-08 00:00:00

  • Dynamic changes in myocardial matrix and relevance to disease: translational perspectives.

    abstract::The cardiac extracellular matrix (ECM) provides the architectural scaffold to support efficient contraction and relaxation of cardiomyocytes. The elegant design of the ECM facilitates optimal force transduction, electric transmission, intercellular communication, and metabolic exchange within the myocardial microenvir...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.114.302819

    authors: Li AH,Liu PP,Villarreal FJ,Garcia RA

    更新日期:2014-02-28 00:00:00

  • Reduction of canine myocardial infarct size by a diffusible reactive oxygen metabolite scavenger. Efficacy of dimethylthiourea given at the onset of reperfusion.

    abstract::A number of scavengers of reactive oxygen metabolites reduce myocardial injury when given before ischemia and reperfusion, but few, if any, have proven to be effective when given near the onset of reperfusion. This is particularly true when infarct size is measured after at least 48 hours of reperfusion, when the full...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.6.1652

    authors: Carrea FP,Lesnefsky EJ,Repine JE,Shikes RH,Horwitz LD

    更新日期:1991-06-01 00:00:00

  • Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes.

    abstract::3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide. However, it is unclear whether statins can exert such effects directly on cardiac myocytes and whether mitochondria...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000097262.21507.DF

    authors: Jones SP,Teshima Y,Akao M,Marbán E

    更新日期:2003-10-17 00:00:00

  • The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489.

    abstract:RATIONALE:Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biolo...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.114.302476

    authors: Wang K,Liu F,Zhou LY,Long B,Yuan SM,Wang Y,Liu CY,Sun T,Zhang XJ,Li PF

    更新日期:2014-04-25 00:00:00

  • Mechanisms of automaticity in subsidiary pacemakers from cat right atrium.

    abstract::Intracellular recordings were made from eustachian ridge of cat right atrium to determine mechanisms responsible for subsidiary pacemaker automaticity. Pacemaker action potentials exhibited two phases of diastolic depolarization: an initial steeper slope (D1) followed by a more gradual slope (D2). Cesium (1 mM) decrea...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.64.4.648

    authors: Rubenstein DS,Lipsius SL

    更新日期:1989-04-01 00:00:00

  • Responses of the heart to stimulation of aortic body chemoreceptors in dogs.

    abstract::We stimulated the aortic chemoreceptors in dogs that were anesthetized with chloralose and artificially ventilated by perfusing the isolated aortic arch with venous blood. Inotropic responses were determined by measuring the maximum rate of change of left ventricular pressure (dP/dt max) with aortic pressure and heart...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.46.1.77

    authors: Karim F,Hainsworth R,Sofola OA,Wood LM

    更新日期:1980-01-01 00:00:00

  • Early expression of myocardial HIF-1alpha in response to mechanical stresses: regulation by stretch-activated channels and the phosphatidylinositol 3-kinase signaling pathway.

    abstract::Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia-inducible factor-1 (HIF-1) in ischemic tissues and growing tumors. Normally, HIF-1 activity depends on the amount of HIF-1alpha subunit, which is tightly regulated by the oxygen tension. In the myocardium, VEGF expression has been shown to ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh0202.104923

    authors: Kim CH,Cho YS,Chun YS,Park JW,Kim MS

    更新日期:2002-02-08 00:00:00

  • Enhancement of potassium-sensitive current in heart cells by pinacidil. Evidence for modulation of the ATP-sensitive potassium channel.

    abstract::Pinacidil belongs to a novel group of compounds that enhance the potassium permeability of vascular smooth muscle. Evidence also exists that this drug enhances the potassium permeability of cardiac tissue. The purpose of the present investigation was to determine if pinacidil alters potassium-channel activity in heart...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.2.436

    authors: Arena JP,Kass RS

    更新日期:1989-08-01 00:00:00

  • GDF11 does not rescue aging-related pathological hypertrophy.

    abstract:RATIONALE:Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family of secreted factors. A recent study showed that reduced GDF11 blood levels with aging was associated with pathological cardiac hypertrophy (PCH) and restoring GDF11 to normal levels in old mice rescued PCH. ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.307527

    authors: Smith SC,Zhang X,Zhang X,Gross P,Starosta T,Mohsin S,Franti M,Gupta P,Hayes D,Myzithras M,Kahn J,Tanner J,Weldon SM,Khalil A,Guo X,Sabri A,Chen X,MacDonnell S,Houser SR

    更新日期:2015-11-06 00:00:00

  • Myocyte enhancer factor 2 mediates vascular inflammation via the p38-dependent pathway.

    abstract::Although it has been established that myocyte enhancer factor 2 (MEF2) plays pivotal roles in the development of the cardiovascular system as well as skeletal muscle cells, little is known of its role in vascular inflammatory diseases such as atherosclerosis and restenosis after angioplasty. To investigate the role of...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000134631.75684.4A

    authors: Suzuki E,Satonaka H,Nishimatsu H,Oba S,Takeda R,Omata M,Fujita T,Nagai R,Hirata Y

    更新日期:2004-07-09 00:00:00

  • Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion.

    abstract::In clinical trials, aldosterone antagonists decrease cardiovascular mortality and ischemia by unknown mechanisms. The steroid hormone aldosterone acts by binding to the mineralocorticoid receptor (MR), a ligand-activated transcription factor. In humans, aldosterone causes MR-dependent endothelial cell (EC) dysfunction...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.108.174235

    authors: Caprio M,Newfell BG,la Sala A,Baur W,Fabbri A,Rosano G,Mendelsohn ME,Jaffe IZ

    更新日期:2008-06-06 00:00:00

  • Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice.

    abstract::To test the hypothesis that early interventional treatment with insulin-like growth factor-1 (IGF-1) alleviates subsequent development of dilated cardiomyopathy, cardiac-specific IGF-1 expression was introduced by selective cross-breeding into a transgenic mouse model of heart failure that displays phenotypic characte...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.0000013780.77774.75

    authors: Welch S,Plank D,Witt S,Glascock B,Schaefer E,Chimenti S,Andreoli AM,Limana F,Leri A,Kajstura J,Anversa P,Sussman MA

    更新日期:2002-04-05 00:00:00

  • Noise-free visualization of microscopic calcium signaling by pixel-wise fitting.

    abstract:RATIONALE:Our insights into physiological and pathophysiological cardiac excitation-contraction coupling has greatly benefited from significant advancement in optical technologies such as high-speed confocal microscopy. This has pushed pixel dwell times into the time domain of nanoseconds, resulting in low signal-to-no...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.112.266403

    authors: Tian Q,Kaestner L,Lipp P

    更新日期:2012-06-22 00:00:00

  • Autoregulation of blood flow within individual arterioles in the rat cremaster muscle.

    abstract::Autoregulatory responses to alterations in arterial or venous perfusion pressure were determined for individual arterioles within the rat cremaster muscle. The cremaster muscle of pentobarbital anesthetized rats (50 mg/kg, ip) was surgically exposed and maintained in a controlled tissue bath for visualization by in vi...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.51.1.43

    authors: Morff RJ,Granger HJ

    更新日期:1982-07-01 00:00:00

  • Aldosterone upregulates Ca(2+) current in adult rat cardiomyocytes.

    abstract::Aldosterone is associated with the pathogenesis and progression of left ventricular hypertrophy and heart failure, independent of its relation with arterial blood pressure. However, little information exists about the possible influence of this mineralocorticoisteroid on cardiomyocyte electrical activity. The present ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.85.12.1139

    authors: Bénitah JP,Vassort G

    更新日期:1999-12-03 00:00:00

  • Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart.

    abstract:RATIONALE:Chronic rejection, accelerated coronary atherosclerosis, myocardial infarction, and ischemic heart failure determine the unfavorable evolution of the transplanted heart in humans. OBJECTIVE:Here we tested whether the pathological manifestations of the transplanted heart can be corrected partly by a strategy ...

    journal_title:Circulation research

    pub_type: 杂志文章,收录出版

    doi:10.1161/CIRCRESAHA.109.207266

    authors: D'Alessandro DA,Kajstura J,Hosoda T,Gatti A,Bello R,Mosna F,Bardelli S,Zheng H,D'Amario D,Padin-Iruegas ME,Carvalho AB,Rota M,Zembala MO,Stern D,Rimoldi O,Urbanek K,Michler RE,Leri A,Anversa P

    更新日期:2009-11-20 00:00:00

  • Hemodynamic performance and myosin light chain-1 expression of the hypertrophied left ventricle in aortic valve disease before and after valve replacement.

    abstract::Previously, we have reported on the selective accumulation of an atrial-like myosin light chain-1 (ALC1) in different forms of human ventricular hypertrophy. The present study involves the determination of ALC1 content in a control group and in patients with aortic stenosis or insufficiency before and 56 +/- 23 months...

    journal_title:Circulation research

    pub_type: 临床试验,杂志文章

    doi:10.1161/01.res.70.5.1035

    authors: Sütsch G,Brunner UT,von Schulthess C,Hirzel HO,Hess OM,Turina M,Krayenbuehl HP,Schaub MC

    更新日期:1992-05-01 00:00:00