DOCSLIB.ORG

Novel Antithrombotic Therapies for the Prevention of Stroke in Patients with Atrial Fibrillation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Novel Antithrombotic Therapies for the Prevention of Stroke in Patients with Atrial Fibrillation REPORTS Novel Antithrombotic Therapies for the Prevention of Stroke in Patients With Atrial Fibrillation Martin O’Donnell, MB; and Jeffrey I. Weitz, MD Abstract incidence of AF in men ranges from 0.2% per Atrial fibrillation (AF), the most common type of year for men 30 to 39 years of age to 2.3% arrhythmia in adults, is a major risk factor for stroke. per year for men between the ages of 80 and The prevalence of AF increases with age, occurring 89 years.8,9 In women, the age-adjusted inci- in 1% of persons <60 years of age and in almost 10% dence is half that in men.7 of those >80 years of age. Recent studies show that A predisposing condition is found in 90% treatment strategies that combine control of ventricu- 10,11 lar rate with antithrombotic therapy are as effective of patients with AF. These include car- as strategies aimed at restoring sinus rhythm. Current diac and noncardiac causes. The most com- antithrombotic therapy regimens in patients with AF mon cardiac conditions associated with AF involve chronic anticoagulation with dose-adjusted are hypertension, rheumatic mitral valve vitamin K antagonists unless patients have a con- disease, coronary artery disease, and con- traindication to these agents or are at low risk for gestive heart failure (CHF).12 Noncardiac stroke. Patients with AF at low risk for stroke may causes include hyperthyroidism, hypoxic benefit from aspirin. Although vitamin K antagonists pulmonary conditions, surgery, and alcohol are effective, their use is problematic, highlighting intoxication.12 The 10% of patients without a the need for new antithrombotic strategies. predisposing cause are said to have lone AF. This article will (a) provide an overview of the Patients with AF may present with symp- clinical trials that form the basis for current antithrombotic guidelines in patients with AF, (b) toms ranging from palpitations associated highlight the limitations of current antithrombotic with a feeling of malaise to those of hemody- drugs used for stroke prevention, (c) briefly review namic compromise. However, the most the pharmacology of new antithrombotic drugs feared complication of AF is thromboem- under evaluation in AF, (d) describe ongoing trials bolism, which can present as a stroke or with new antiplatelet therapies and idraparinux, and systemic embolic event.12 Compared with completed studies with ximelagatran in patients with age-matched controls, patients with nonval- AF, and (e) provide clinical perspective into the vular AF have a 2- to 7-fold increased risk of potential role of new antithrombotic drugs in AF. stroke with the absolute risk of stroke rang- (Am J Manag Care. 2004;10:S72-S82) ing from 1% to about 5% per year depending on the absence or presence of clinical risk factors.3,9,13-15 Factors that increase the risk of stroke include patient age of ≥75 years, CHF, hypertension (systolic or diastolic), diabetes mellitus, and past history of a car- trial fibrillation (AF), the most com- dioembolic event (transient ischemic attack, mon arrhythmia in adults, accounts stroke, or systemic embolism).16,17 In pa- for about one third of hospital admis- tients presenting with acute ischemic A 1 sions for cardiac arrhythmias. The preva- stroke, AF is found in up to 20%, and its lence of AF increases with age, increasing presence is associated with a 2-fold increase from 1% in those <60 years of age to almost in mortality.18 10% in persons >80 years of age.2-6 When Because of the risk of thromboembolism adjustments are made for age, AF is more in patients with AF, a major part of treat- common in men than in women.7 Thus, the ment is the use of measures to reduce the S72 THE AMERICAN JOURNAL OF MANAGED CARE APRIL 2004 Novel Antithrombotic Therapies for the Prevention of Stroke in Patients With Atrial Fibrillation risk of stroke. One obvious question is of antiplatelet drugs, aspirin plus clopido- whether conversion to sinus rhythm lowers grel, ximelagatran, the first oral direct the risk of thromboembolism in patients thrombin inhibitor, and idraparinux, a par- with AF. Recently, 4 studies have addressed enteral, long-acting synthetic pentasaccha- this question by examining whether rate ride.23 This paper will (a) provide an control or rhythm control provides more overview of the clinical trials that form the effective protection against thromboembolic basis for current antithrombotic guidelines events, reduces mortality, and offers better in patients with AF, (b) highlight the limi- relief of symptoms or improved quality of tations of current antithrombotic drugs, (c) life.19-22 All 4 of these studies focused mainly briefly review the pharmacology of new on patients >65 years of age with at least 1 antithrombotic drugs, (d) describe ongoing risk factor for stroke. The largest study, the trials with new antiplatelet therapies and Atrial Fibrillation Follow-Up Investigation of idraparinux, and completed studies with Rhythm Management (AFFIRM) trial,19 ran- ximelagatran in AF patients, and (e) pro- domized 4060 such patients to rate or vide clinical perspective into the potential rhythm control. Anticoagulation was contin- role of new antithrombotic drugs for ued indefinitely in the rate control group patients with AF. and was encouraged in the rhythm control group, but could be stopped if sinus rhythm Current Status of Antithrombotic was maintained for at least 4, but preferably Therapy in AF 6 consecutive weeks. The prevalence of Meta-analyses of primary prevention sinus rhythm in the rhythm control group studies indicate that warfarin is more effec- was 82%, 73%, and 63% at 1, 3, and 5 years, tive than placebo for prevention of stroke respectively, whereas its prevalence in the and systemic embolism in AF patients (odds rate control group was 35% at 5 years.19 ratio [OR], 0.31; 95% CI, 0.19-0.48; P The primary end point, overall mortality <.001), but is associated with a trend for an at 5 years, was 23.8% and 21.3% in the increased risk of major bleeding (OR, 1.9; rhythm control and rate control groups, 95% CI, 0.89-4.00; P=.1).22 Compared with respectively (hazard ratio, 1.15; 95% confi- placebo for primary prevention, aspirin also dence interval [CI], 0.99-1.24; P=.008). reduces the risk of stroke and systemic Rates of stroke were 8.9% and 7.4% in the embolism (OR, 0.68; 95% CI, 0.46-1.02; rhythm control and rate control groups, P=.06), without clear evidence of an respectively (P <.2), and >70% of strokes in increased risk of major bleeding (OR, 0.82; both groups occurred in patients who had 95% CI, 0.37-1.78; P >.2).22 When warfarin is stopped anticoagulant therapy, or in those compared with aspirin, warfarin produces a whose international normalized ratio (INR) greater reduction in stroke and systemic was <2.0.19 Thus, patients in the AFFIRM embolism (OR, 0.66; 95% CI, 0.45-0.99; P trial19 showed no improvement in mortality =.04), without conclusive evidence of more or morbidity with aggressive rhythm con- major bleeding (OR, 1.61; 95% CI, 0.75-3.44; trol; findings that have been confirmed in 3 P>.2).22 For primary prevention, adjusting smaller randomized clinical trials.20-22 These the dose of warfarin to produce an INR of 2.0 data indicate that a strategy that combines to 3.0 appears to be more effective than low- rate control with antithrombotic therapy is dose warfarin regimens that target an INR of as effective as rhythm control in most 1.1 to 1.6 (OR, 0.52; 95% CI, 0.25-1.08; patients with AF. P=.08), even when low-dose warfarin is At present, options for antithrombotic combined with aspirin (OR, 0.44; 95% CI, therapy in patients with AF are limited to 0.14-1.39; P=.16).22 aspirin and/or vitamin K antagonists, the Two trials evaluated warfarin or aspirin most common of which is warfarin.17 for secondary prevention, enrolling AF However, this is likely to change in the near patients who already had suffered a stroke future as the role of new antithrombotic reg- or transient ischemic attack.24,25 In the imens is established in patients with AF. largest trial,24 patients were stratified These novel regimens include a combination according to their eligibility for warfarin VOL. 10, NO. 3, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S73 REPORTS Table 1. Annual Risk of Stroke in National Stroke Registry of Atrial Fibrillation (NRAF) Applied to Different Stroke Risk-Stratification Schemes AFI SPAF CHADS2 Risk factor Low risk = no risk factors Low risk = no risk factors 1 point for each of the classification Moderate risk = age >65 years Moderate risk = hypertension following: recent CHF, High risk = prior ischemic event, High risk = prior ischemic event, hypertension, age ≥75 years, hypertension and DM women >75 years, recent CHF or DM or LVF 25%, SBP >160 mm Hg 2 points for prior cerebral ischemic event NRAF stroke rate (%) per 100 patient-years (95% confidence interval)61 Low — 1.5 (0.5-2.8) 0 1.9 (1.2-3.0) 1 2.8 (2.0-3.8) Moderate 2.2 (1.1-3.5) 3.3 (1.7-5.2) 2 4.0 (3.1-5.1) 3 5.9 (4.6-7.3) High 5.4 (4.2-6.5) 5.7 (4.4-7.0) 4 8.5 (6.3-11.1) 5 12.5 (8.2-17.5) 6 18.2 (10.5-27.4) AFI indicates Atrial Fibrillation Investigators; SPAF, Stroke Prevention in Atrial Fibrillation trial; CHADS2, Congestive Heart Failure, Hypertension, Age, Diabetes, and Stroke; DM, diabetes mellitus; CHF, congestive heart failure; LVF, left ventricular function; SBP, systolic blood pressure.
Load more

Recommended publications
  • 202439Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 202439Orig1s000 MEDICAL REVIEW(S) Clinical Review: Nhi Beasley, Preston Dunnmon and Martin Rose Application type: Standard, NDA 22-439 Xarelto (rivaroxaban) CLINICAL REVIEW Application Type NDA Type 1 -- (505(b)(1)) Application Number(s) 202439 Priority or Standard Standard Submit Date(s) 4 January 2011 Received Date(s) 5 January 2011 PDUFA Goal Date 5 November 2011 Division / Office DCRP/ODE 1 Reviewer Name(s) Nhi Beasley, Preston Dunnmon (safety); Martin Rose (efficacy) Review Completion Date 10 August 2011 Established Name Rivaroxaban Trade Name Xarelto® Therapeutic Class Anticoagulant (factor Xa inhibitor) Applicant Johnson & Johnson Pharmaceutical Research & Development, LLC Formulation(s) Oral tablets – 15 & 20 mg Dosing Regimen 15 or 20 mg once daily, based on renal function Indication(s) Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation Intended Population(s) Adults Template Version: March 6, 2009 1 Reference ID: 2998874 Clinical Review: Nhi Beasley, Preston Dunnmon and Martin Rose Application type: Standard, NDA 22-439 Xarelto (rivaroxaban) Note to Readers In this review, a high level summary of the efficacy, safety and risk-benefit data is found in Section 1.2 Individual summaries of the efficacy and safety data are found at the beginning of Section 6 and Section 7, respectively. Internal hyperlinks to other parts of the review are in blue font. The Tables of Contents, Tables, and Figures are also hyperlinked to their targets. Table of Contents NOTE TO READERS ...................................................................................................... 2 TABLE OF CONTENTS .................................................................................................. 2 1 RECOMMENDATIONS/RISK BENEFIT ASSESSMENT ....................................... 10 1.1 Recommendation on Regulatory Action ..........................................................
    [Show full text]
  • Heparin EDTA Patent Application Publication Feb
    US 20110027771 A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0027771 A1 Deng (43) Pub. Date: Feb. 3, 2011 (54) METHODS AND COMPOSITIONS FORCELL Publication Classification STABILIZATION (51) Int. Cl. (75)75) InventorInventor: tDavid Deng,eng, Mountain rView, V1ew,ar. CA C09KCI2N 5/073IS/00 (2006.01)(2010.01) C7H 2L/04 (2006.01) Correspondence Address: CI2O 1/02 (2006.01) WILSON, SONSINI, GOODRICH & ROSATI GOIN 33/48 (2006.01) 650 PAGE MILL ROAD CI2O I/68 (2006.01) PALO ALTO, CA 94304-1050 (US) CI2M I/24 (2006.01) rsr rr (52) U.S. Cl. ............ 435/2; 435/374; 252/397:536/23.1; (73) Assignee: Arts Health, Inc., San Carlos, 435/29: 436/63; 436/94; 435/6: 435/307.1 (21) Appl. No.: 12/847,876 (57) ABSTRACT Fragile cells have value for use in diagnosing many types of (22) Filed: Jul. 30, 2010 conditions. There is a need for compositions that stabilize fragile cells. The stabilization compositions of the provided Related U.S. Application Data inventionallow for the stabilization, enrichment, and analysis (60) Provisional application No. 61/230,638, filed on Jul. of fragile cells, including fetal cells, circulating tumor cells, 31, 2009. and stem cells. 14 w Heparin EDTA Patent Application Publication Feb. 3, 2011 Sheet 1 of 17 US 2011/0027771 A1 FIG. 1 Heparin EDTA Patent Application Publication Feb. 3, 2011 Sheet 2 of 17 US 2011/0027771 A1 FIG. 2 Cell Equivalent/10 ml blood P=0.282 (n=11) 1 hour 6 hours No Composition C Composition C Patent Application Publication Feb.
    [Show full text]
  • Low Molecular Weight Heparin
    LOW MOLECULAR WEIGHT HEPARIN (LMWH) AHFS ??? Indications: Prevention and treatment of deep vein thrombosis, pulmonary embolism, †thrombophlebitis migrans, †disseminated intravascular coagulation (DIC). Contra-indications: Active major bleeding, history of heparin-induced thrombocytopenia with unfractionated heparin, thrombocytopenia with positive anti- platelet antibody test, severe renal impairment ( certoparin, reviparin (not USA)). Pharmacology Several different varieties of low molecular weight heparin (LMWH) are now available (e.g. bemiparin , certoparin , dalteparin , enoxaparin , reviparin and tinzaparin ). Most are approved for the prevention of venous thrombo-embolism and some are also indicated for the treatment of deep vein thrombosis, pulmonary embolism, unstable coronary artery disease and for the prevention of clotting in extracorporeal circuits. All LMWH is derived from porcine heparin and some patients may need to avoid them because of hypersensitivity, or for religious or cultural reasons. The most appropriate non-porcine alternative is fondaparinux . LMWH acts by potentiating the inhibitory effect of antithrombin III on Factor Xa and thrombin. It has a relatively higher ability to potentiate Factor Xa inhibition than to prolong plasma clotting time (APTT) which cannot be used to guide dosage. Anti- factor Xa levels can be measured if necessary but routine monitoring is not required because the dose is determined by the patient’s weight. LMWH is as effective as unfractionated heparin for the treatment of deep vein thrombosis and pulmonary embolism and is now considered the initial treatment of choice. 1,2 Other advantages include a longer duration of action which allows administration q.d., and possibly a better safety profile, e.g. fewer major hemorrhages. 1-5 LMWH is the treatment of choice for chronic DIC; this commonly presents as recurrent thromboses in both superficial and deep veins which do not respond to warfarin .
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr
    US008158152B2 (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr. 17, 2012 (54) LYOPHILIZATION PROCESS AND 6,884,422 B1 4/2005 Liu et al. PRODUCTS OBTANED THEREBY 6,900, 184 B2 5/2005 Cohen et al. 2002fOO 10357 A1 1/2002 Stogniew etal. 2002/009 1270 A1 7, 2002 Wu et al. (75) Inventor: Nageswara R. Palepu. Mill Creek, WA 2002/0143038 A1 10/2002 Bandyopadhyay et al. (US) 2002fO155097 A1 10, 2002 Te 2003, OO68416 A1 4/2003 Burgess et al. 2003/0077321 A1 4/2003 Kiel et al. (73) Assignee: SciDose LLC, Amherst, MA (US) 2003, OO82236 A1 5/2003 Mathiowitz et al. 2003/0096378 A1 5/2003 Qiu et al. (*) Notice: Subject to any disclaimer, the term of this 2003/OO96797 A1 5/2003 Stogniew et al. patent is extended or adjusted under 35 2003.01.1331.6 A1 6/2003 Kaisheva et al. U.S.C. 154(b) by 1560 days. 2003. O191157 A1 10, 2003 Doen 2003/0202978 A1 10, 2003 Maa et al. 2003/0211042 A1 11/2003 Evans (21) Appl. No.: 11/282,507 2003/0229027 A1 12/2003 Eissens et al. 2004.0005351 A1 1/2004 Kwon (22) Filed: Nov. 18, 2005 2004/0042971 A1 3/2004 Truong-Le et al. 2004/0042972 A1 3/2004 Truong-Le et al. (65) Prior Publication Data 2004.0043042 A1 3/2004 Johnson et al. 2004/OO57927 A1 3/2004 Warne et al. US 2007/O116729 A1 May 24, 2007 2004, OO63792 A1 4/2004 Khera et al.
    [Show full text]
  • New Anticoagulants for Atrial Fibrillation
    New Anticoagulants for Atrial Fibrillation Magdalena Sobieraj-Teague, M.B.B.S.,1 Martin O’Donnell, M.B.,1 and John Eikelboom, M.B.B.S.1 ABSTRACT Atrial fibrillation is already the most common clinically significant cardiac arrhythmia and a common cause of stroke. Vitamin K antagonists are very effective for the prevention of cardioembolic stroke but have numerous limitations that limit their uptake in eligible patients with AF and reduce their effectiveness in treated patients. Multiple new anticoagulants are under development as potential replacements for vitamin K antagonists. Most are small synthetic molecules that target factor IIa (e.g., dabigatran etexilate, AZD-0837) or factor Xa (e.g., rivaroxaban, apixaban, betrixaban, DU176b, idrabiotaparinux). These drugs have minimal protein binding and predictable pharmaco- kinetics that allow fixed dosing without laboratory monitoring and are being compared with vitamin K antagonists or aspirin in phase III clinical trials. A new vitamin K antagonist (ATI-5923) with improved pharmacological properties compared with warfarin is also being evaluated in a phase III trial. None of the new agents have as yet been approved for clinical use. KEYWORDS: Atrial fibrillation, anticoagulants, stroke, factor Xa inhibitor, direct thrombin inhibitor Atrial fibrillation (AF) is the most common aspirin,3,8,9 and they are recommended for patients at a clinically significant cardiac arrhythmia. The prevalence moderate to high risk of stroke, which accounts for of AF increases with age, approaching 10% in those >70%
    [Show full text]
  • Treatment of Venous Thromboembolism: the Single-Drug Approach
    Review Treatment of venous thromboembolism: the single-drug approach Paolo Prandoni*1, Sofia Barbar1, Valentina Vedovetto1, Marta Milan1, Lucia Filippi1, Elena Campello1 & Luca Spiezia1 Practice Points An anticoagulant that is effective for both acute and long-term treatment of venous thromboembolism (VTE) is clearly beneficial and avoids the need for any form of bridging therapy. Of the old and new anticoagulants, the results of randomized clinical trials in support of the ‘single-drug’ approach for the treatment of both patients with deep vein thrombosis and those with hemodynamically stable pulmonary embolism are, to date, only available for rivaroxaban and apixaban (direct inhibitors of factor Xa). The oral administration of rivaroxaban (15 mg twice a day for the first 3 weeks, followed by 20 mg once daily for 3–12 months) or apixaban (10 mg twice a day for 7 days, followed by 5 mg twice a day for 6 months) in patients with acute VTE, is associated with a benefit-to-risk ratio that is at least comparable with that provided by the conventional treatment with enoxaparin followed by vitamin K antagonists. Both rivaroxaban and apixaban qualifiy as suitable compounds for the single-drug treatment of VTE. SUMMARY An anticoagulant that is effective for both acute and long-term treatment of venous thromboembolism is clearly beneficial and avoids the need for any form of overlapping therapy. Among the emerging oral antithrombotic compounds that have the potential to inhibit either factor Xa (rivaroxaban, apixaban and edoxaban) or factor IIa (dabigatran etexilate), and do not require laboratory monitoring, rivaroxaban and apixaban are the only ones to date for which there is persuasive evidence coming from randomized clinical trials in support of the 1Department of Cardiothoracic & Vascular Sciences, Clinica Medica 2, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy *Author for correspondence: Tel.: +39 049 821 2656; Fax: +39 049 821 8731; [email protected] part of 10.2217/CPR.13.31 © 2013 Future Medicine Ltd Clin.
    [Show full text]
  • NIH Public Access Author Manuscript J Thromb Haemost
    NIH Public Access Author Manuscript J Thromb Haemost. Author manuscript; available in PMC 2009 April 20. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: J Thromb Haemost. 2007 July ; 5(Suppl 1): 102±115. doi:10.1111/j.1538-7836.2007.02516.x. Serpins in thrombosis, hemostasis and fibrinolysis J. C. RAU*,1, L. M. BEAULIEU*,1, J. A. HUNTINGTON†, and F. C. CHURCH* *Department of Pathology and Laboratory Medicine, Carolina Cardiovascular Biology Center, School of Medicine, University of North Carolina, Chapel Hill, NC, USA †Department of Haematology, Division of Structural Medicine, Thrombosis Research Unit, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC, Cambridge, UK Summary Hemostasis and fibrinolysis, the biological processes that maintain proper blood flow, are the consequence of a complex series of cascading enzymatic reactions. Serine proteases involved in these processes are regulated by feedback loops, local cofactor molecules, and serine protease inhibitors (serpins). The delicate balance between proteolytic and inhibitory reactions in hemostasis and fibrinolysis, described by the coagulation, protein C and fibrinolytic pathways, can be disrupted, resulting in the pathological conditions of thrombosis or abnormal bleeding. Medicine capitalizes on the importance of serpins, using therapeutics to manipulate the serpin-protease reactions for the treatment and prevention of thrombosis and hemorrhage. Therefore, investigation of serpins, their cofactors, and their structure-function relationships is imperative for the development of state-of- the-art pharmaceuticals for the selective fine-tuning of hemostasis and fibrinolysis. This review describes key serpins important in the regulation of these pathways: antithrombin, heparin cofactor II, protein Z-dependent protease inhibitor, α1-protease inhibitor, protein C inhibitor, α2-antiplasmin and plasminogen activator inhibitor-1.
    [Show full text]
  • ( 12 ) United States Patent
    US009861662B2 (12 ) United States Patent (10 ) Patent No. : US 9 ,861 , 662 B2 Badylak et al. ( 45) Date of Patent : Jan . 9 , 2018 8( 54 ) BONE - DERIVED EXTRA CELLULAR 5 , 762, 966 A 6 / 1998 Knapp , Jr. et al . 5 , 866 ,414 A 2 / 1999 Badylak et al. MATRIX GEL 6 ,099 , 567 A 8 /2000 Badylak et al. 6 , 485 , 723 B1 11 /2002 Badylak et al. ( 71 ) Applicants : University of Pittsburgh — Of the 6 , 576 , 265 B1 6 /2003 Spievack Commonwealth System of Higher 6 , 579 , 538 B1 6 / 2003 Spievack Education , Pittsburgh , PA (US ) ; The 6 , 696 , 270 B2 2 / 2004 Badylak et al. University of Nottingham , Nottingham 6 , 783 , 776 B2 8 / 2004 Spievack 6 , 793 , 939 B2 9 /2004 Badylak (GB ) 6 , 849 , 273 B2 2 / 2005 Spievack 6 , 852 , 339 B2 2 / 2005 Spievack 8(72 ) Inventors : Stephen F . Badylak , Pittsburgh , PA 6 , 861 , 074 B2 3 / 2005 Spievack (US ) ; Michael J . Sawkins, Nottingham 6 , 887 , 495 B2 5 / 2005 Spievack (GB ) ; Kevin M . Shakesheff , 6 , 890 , 562 B2 5 /2005 Spievack 6 , 890 , 563 B2 5 / 2005 Spievack Nottingham (GB ) ; Lisa J . White , 6 , 890 , 564 B2 5 / 2005 Spievack Nottingham (GB ) 6 , 893 ,666 B2 5 /2005 Spievack 2005/ 0013872 A1* 1 / 2005 Freyman .. .. .. .. .. .. A61K 35 / 28 8( 73 ) Assignees : University of Pittsburgh - Of the 424 / 549 Commonwealth System of Higher 2011/ 0195052 A1 * 8 / 2011 Behnam .. .. .. .. .. A61L 27 / 227 Education , Pittsburgh , PA (US ) ; The 424 /93 . 6 University of Nottingham , Nottingham (GB ) OTHER PUBLICATIONS ( * ) Notice : Subject to any disclaimer, the term of this Russell et al.
    [Show full text]
  • Sobieraj-2015.Pdf
    Thrombosis Research 135 (2015) 888–896 Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres Regular Article Comparative efficacy and safety of anticoagulants and aspirin for extended treatment of venous thromboembolism: A network meta-analysis Diana M. Sobieraj a, Craig I. Coleman a,⁎, Vinay Pasupuleti b,AbhishekDeshpandec, Roop Kaw d,AdrianV.Hernandeze a University of Connecticut School of Pharmacy, Department of Pharmacy Practice, 69 North Eagleville Rd Unit 3092, Storrs, CT 06269, USA b Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA c Medicine Institute Center for Value Based Care Research, Cleveland Clinic, Cleveland, OH, USA d Department of Hospital Medicine & Outcomes Research, Anesthesiology, Cleveland Clinic, Cleveland, OH, USA e Medical School, Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru, Health Outcomes and Clinical Epidemiology Section, Dept. of Quantitative Health Sciences, Lerner, Research Institute, Cleveland Clinic, Cleveland, OH, USA article info abstract Article history: Objective: To systematically review the literature and to quantitatively evaluate the efficacy and safety of extend- Received 15 December 2014 ed pharmacologic treatment of venous thromboembolism (VTE) through network meta-analysis (NMA). Received in revised form 6 February 2015 Methods: A systematic literature search (MEDLINE, Embase, Cochrane CENTRAL, through September 2014) and Accepted 24 February 2015 searching of reference lists of included studies and relevant reviews was conducted to identify randomized Available online 4 March 2015 controlled trials of patients who completed initial anticoagulant treatment for VTE and then randomized for the extension study; compared extension of anticoagulant treatment to placebo or active control; and reported Keywords: at least one outcome of interest (VTE or a composite of major bleeding or clinically relevant non-major bleeding).
    [Show full text]
  • Direct Oral Anticoagulants
    Direct Oral Anticoagulants A Comprehensive History and Current Developments BCSLS Telehealth Seminar, Vancouver, BC June 26, 2018 Terence M. Litavec B.Sc., MLT(CSMLS), SHCM(ASCP)HCM,MLTCM,HTLCM(ASCP)QIHCCM Acknowledgements: 2017-2018 KGH Student Interns British Columbia College of New Institute of Caldonia, Technology, Burnaby Prince George Stefani Guidi, MLT Soraya Hadjirul, MLT Henry Lu, MLT Neelam Lilly, MLT Jenna Zhang, MLT Alix Savoy, MLT Dawny Tabilangan, MLT Overview and Objectives (A Work In Progress) Provide background information about the classification and function of DOAC’s Outline the various subtypes of DOAC’s listing their similarities and differences List the brief histories and the most current advances in the field of DOAC drug development Discuss the abnormalities in routine screening coagulation assays for patients taking DOAC’s Describe the laboratory assays used to measure the level of DOAC medication in plasma samples Direct Oral Anticoagulants (DOAC) A new class of drugs to treat and prevent thrombosis related to: Acute Coronary Syndrome (ACS), Atrial Fibrillation (AF), Cerebrovascular Accident (CVA), Myocardial Infarction (MI), Joint Replacement, etc. Can be given as an immediate treatment for an acute crisis, or as a long-term anticoagulant regiment Can be given as alternatives to traditional “clot- busting” medications in patients who have developed sensitivities to Heparin (HIT antibody formation) or Warfarin (Coumadin-related limb gangrene due to Protein C inhibition) Do not require scheduled
    [Show full text]
  • Indirect and Direct Anticoagulants Predominantly Inhibiting Factor Xa
    REVIEW Indirect and direct anticoagulants predominantly inhibiting factor Xa Job Harenberg Synthetic or natural indirect and synthetic direct factor Xa inhibitors with specific actions University of Heidelberg, Institute of Experimental and on only factor Xa are currently in clinical development. The aim of these compounds is to Clinical Pharmacology, improve the antithrombotic therapy when compared with heparins and vitamin K Faculty of Medicine, Ruprecht antagonists, which are characterized by multiple and partially unpredictable actions. The Karls University Heidelberg, Theodor Kutzer Ufer 1-3, indirect factor inhibitors have to be administered parenterally, which is in contrast to the D-68167 Mannheim, direct inhibitors of factor Xa, which may be given orally. This review describes the results of Germany recent dose studies of these two classes of inhibitors of blood coagulation, for the Tel.: +49 621 383 3378 Fax: +49 621 383 3808 prevention and treatment of arterial and venous thromboembolism. E-mail: job.harenberg@ med.ma.uni-heidelberg.de Thromboembolic diseases are treated using imme- act more upstream in the coagulation cascade diate-acting unfractionated heparins (UFH), low- compared with thrombin inhibitors. Small, indi- molecular-weight heparins (LMWH) and fonda- rect antithrombin-dependent inhibitors inhibit parinux, followed by slowly acting oral vitamin K factor Xa in plasma, but not factor Xa in the pro- antagonists if long-term prophylaxis is indicated. thrombinase complex or bound to the fibrin clot. Although these drugs have been proven to be effec- Small direct synthetic molecules directed towards tive in reducing the risk of thromboembolic dis- factor Xa and IIa can neutralize their respective tar- ease, they are associated with limitations for gets irrespective of whether the targets are free in clinical use.
    [Show full text]
  • And Factor Xa-Inhibitors for Prevention and Treatment of Thromboses Faktor II- Und Faktor Xa-Inhibitoren in Der Pra¨ Vention Und Therapie Von Thrombosen
    Article in press - uncorrected proof J Lab Med 2009;33(2):121–127 ᮊ 2009 by Walter de Gruyter • Berlin • New York. DOI 10.1515/JLM.2009.023 2009/23 Ha¨ mostaseologie Redaktion: C. Schambeck Factor II- and factor Xa-inhibitors for prevention and treatment of thromboses Faktor II- und Faktor Xa-Inhibitoren in der Pra¨ vention und Therapie von Thrombosen Matthias Orth* tiven Thromboseprophylaxe sowie die Mo¨ glichkeiten eines Dosismonitorings vorgestellt. Vinzenz von Paul Kliniken gGmbH, Institut fu¨r Laboratoriumsmedizin, Stuttgart, Germany Schlu¨ sselwo¨ rter: Anti Xa-Inhibitoren; aPTT; direkte Thrombininhibitoren; Ecarin chromogener Assay; Thera- Abstract piekontrolle; Prothrombinase-induced Clotting Time (PiCT). The desired properties of an ideal anticoagulant should be reliable action, a defined, selective mode of action, a wide therapeutic window, and predictable pharmaco- Introduction kinetics. Numerous new substances were developed as a substitute for oral anticoagulants and heparins. Owing Major surgery, such as total hip replacement and total to their superiority in clinical studies, some of these drugs knee replacement, is associated with a very high risk of have already been approved. The hemostaseological developing deep vein thrombosis (DVT) and pulmonary laboratory is now challenged to detect a sufficient anti- embolism. Certain medical conditions, such as chronic coagulation while avoiding bleeding by overdosing. The atrial fibrillation (AF), are associated with embolic stroke. purpose of this review is to describe novel anticoagulants Therefore, prophylactic anticoagulation is the standard of in current use and the possible tests for drug monitoring care in these patients and is supported by Grade 1A in heparin-induced thrombocytopenia and in the peri- evidence recommendations w1x.
    [Show full text]