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 Resjournal_title
Circulation researchauthors
Chan NC,Eikelboom JW,Weitz JIdoi
10.1161/CIRCRESAHA.116.306925subject
Has Abstractpub_date
2016-04-29 00:00:00pages
1409-24issue
9eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.306925journal_volume
118pub_type
杂志文章,评审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
更新日期:2020-07-17 00:00:00
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
更新日期:2004-05-28 00:00:00
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
更新日期:2016-04-15 00:00:00
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
更新日期:2006-11-24 00:00:00
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
更新日期:1993-12-01 00:00:00
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
更新日期:2009-07-31 00:00:00
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
更新日期:2020-02-14 00:00:00
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
更新日期:2017-12-08 00:00:00
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
更新日期:1998-12-14 00:00:00
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
更新日期:1985-02-01 00:00:00
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
更新日期:1987-07-01 00:00:00
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
更新日期:1998-09-07 00:00:00
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
更新日期:2011-07-08 00:00:00
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
更新日期:2014-02-28 00:00:00
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
更新日期:1991-06-01 00:00:00
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
更新日期:2003-10-17 00:00:00
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
更新日期:2014-04-25 00:00:00
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
更新日期:1989-04-01 00:00:00
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
更新日期:1980-01-01 00:00:00
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
更新日期:2002-02-08 00:00:00
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
更新日期:1989-08-01 00:00:00
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
更新日期:2015-11-06 00:00:00
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
更新日期:2004-07-09 00:00:00
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
更新日期:2008-06-06 00:00:00
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
更新日期:2002-04-05 00:00:00
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
更新日期:2012-06-22 00:00:00
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
更新日期:1982-07-01 00:00:00
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
更新日期:1999-12-03 00:00:00
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
更新日期:2009-11-20 00:00:00
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
更新日期:1992-05-01 00:00:00