DOCSLIB.ORG

Antithrombotic Therapy in Hypertension: a Cochrane Systematic Review

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antithrombotic Therapy in Hypertension: a Cochrane Systematic Review Journal of Human Hypertension (2005) 19, 185–196 & 2005 Nature Publishing Group All rights reserved 0950-9240/05 $30.00 www.nature.com/jhh ORIGINAL ARTICLE Antithrombotic therapy in hypertension: a Cochrane Systematic review DC Felmeden and GYH Lip Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK Although elevated systemic blood pressure (BP) results on one large trial, ASA taken for 5 years reduced in high intravascular pressure, the main complications myocardial infarction (ARR, 0.5%, NNT 200 for 5 years), of hypertension are related to thrombosis rather than increased major haemorrhage (ARI, 0.7%, NNT 154), and haemorrhage. It therefore seemed plausible that use of did not reduce all cause mortality or cardiovascular antithrombotic therapy may be useful in preventing mortality. In two small trials, warfarin alone or in thrombosis-related complications of elevated BP. The combination with ASA did not reduce stroke or coronary objectives were to conduct a systematic review of the events. Glycoprotein IIb/IIIa inhibitors as well as ticlopi- role of antiplatelet therapy and anticoagulation in dine and clopidogrel have not been sufficiently eval- patients with BP, to address the following hypotheses: uated in patients with elevated BP. To conclude for (i) antiplatelet agents reduce total deaths and/or major primary prevention in patients with elevated BP, anti- thrombotic events when compared to placebo or other platelet therapy with ASA cannot be recommended active treatment; and (ii) oral anticoagulants reduce total since the magnitude of benefit, a reduction in myocar- deaths and/or major thromboembolic events when dial infarction, is negated by a harm of similar magni- compared to placebo or other active treatment. A tude, an increase in major haemorrhage. For secondary systematic review of randomised studies in patients prevention in patients with elevated BP, antiplatelet with elevated BP was performed. Studies were included therapy is recommended because the magnitude of the if they were 43 months in duration and compared absolute benefit is many times greater. Warfarin therapy antithrombotic therapy with control or other active alone or in combination with aspirin in patients with treatment. One meta-analysis of antiplatelet therapy for elevated BP cannot be recommended because of lack of secondary prevention in patients with elevated BP demonstrated benefit. Further trials of antithrombotic reported an absolute reduction in vascular events of therapy are required in patients with elevated BP. 4.1% as compared to placebo. Acetylsalicylic acid (ASA) Journal of Human Hypertension (2005) 19, 185–196. did not reduce stroke or ‘all cardiovascular events’ doi:10.1038/sj.jhh.1001807 compared to placebo in primary prevention patients with Published online 27 January 2005 elevated BP and no prior cardiovascular disease. Based Keywords: aspirin; warfarin; antithrombotic therapy Introduction and stroke by more than half.1–3 In middle and old age, there appears to be a direct relationship Although systemic (arterial) hypertension results in between the level of BP and the risk of cardiovas- high intravascular pressure, the main complications cular death without any evidence of a threshold of hypertension, that is, coronary heart disease down to a BP of at least 115/75 mmHg.4 Correspond- (CHD), ischaemic strokes and peripheral vascular ingly, BP reduction trials have shown a reduction in disease (PVD), are related to thrombosis rather than CHD by 16% and stroke by 38%. It should not be haemorrhage. The association between hypertension forgotten that hypertension is a risk factor for both and risk for stroke and CHD almost appears to have a haemorrhagic as well as ischaemic strokes. dose–response relationship, with increasing risk for 1–3 It should be recognised that some of the complica- higher blood pressures (BP). Indeed an increase in tions related to hypertension, such as heart failure or the diastolic blood pressure (DBP) by 10 mmHg is atrial fibrillation, are themselves associated with associated with an increase in CHD risk by one-third stroke and thromboembolism.5 Increasing evidence also points towards a prothrombotic or hypercoagul- Correspondence: Professor GYH Lip, Haemostasis, Thrombosis, able state conferred by the presence of hypertension, and Vascular Biology Unit, University Department of Medicine, as evident by abnormalities of coagulation,6,7 plate- City Hospital, Birmingham, UK. 6,7 8–10 E-mail: [email protected] lets and endothelial function in such patients. Received 18 October 2004; accepted 18 October 2004; published It therefore seems plausible that use of antithrom- online 27 January 2005 botic therapy may help to prevent thrombosis-related Antithrombotic therapy in hypertension DC Felmeden and GYH Lip 186 complications of hypertension.5 The antithrombotic congestive heart failure, pre-eclampsia, eclampsia or agent, aspirin, has long been used in the treatment pulmonary hypertension were excluded. and secondary prevention of many of the complica- tions of hypertension, but until recently little (c) Types of interventions information has been available on its role in the Treatment duration of at least 3 months with management of asymptomatic, hypertensive indivi- antiplatelet agents (aspirin, nonsteroidal anti-in- dual. Warfarin has also been found to be useful as flammatory drugs (NSAIDs), dipyridamole, clopido- thromboprophylaxis in hypertensive patients with grel, glycoprotein IIb/IIIa inhibitors (GPIIb/IIIa atrial fibrillation,11,12 but if blood pressures remain inhibitors) (ie ticlopidine)) or oral anticoagulants uncontrolled, such therapy carries significant risks, (warfarin and other vitamin K antagonist antic- especially from intracranial haemorrhage. oagulants) were included. Available data on con- comitant treatment were collected, where available. Objectives Types of outcome measures A systematic review of the role of antiplatelet therapy and anticoagulation was conducted in (a) Primary outcome measure(s) patients with systemic (arterial) hypertension, in- All cause mortality and cardiovascular mortality cluding those with systodiastolic hypertension, (stroke, myocardial infarction, sudden death, throm- isolated systolic hypertension and diastolic hyper- boembolic events). tension, to address the following hypotheses: (i) antiplatelet agents reduce total deaths and/or major (b) Secondary outcome measure(s) thrombotic events in patients when compared to All nonfatal cardiovascular events (stroke, myocar- placebo or other active treatment; and (ii) oral dial infarction, thromboembolic events such as anticoagulants reduce total deaths and/or major acute coronary syndrome, acute limb ischaemia, thromboembolic events in patients with hyperten- pulmonary embolism, deep vein thrombosis), as a sion when compared to placebo or other active composite end point. All major bleeding events treatment. (fatal, nonfatal) as a composite end point. A major It should be noted that antithrombotic therapy in bleed was defined as haemorrhagic stroke, or major atrial fibrillation11 and heart failure13 per se are blood loss defined as a drop in haemoglobin of considered in detail in separate Cochrane reviews. 42 g/dl with adequate hydration, or urgent transfu- In atrial fibrillation, for example, the presence of sion with final haemoglobin after equilibration of hypertension increases the risk of stroke and less than prebleed level, or orthostatic hypotension, thromboembolism, and such patients are at moder- or supine blood pressure under 90/60 mmHg. ate-to-high risk; hypertension and atrial fibrillation also commonly coexist. (c) Tertiary outcome measure(s) All cardiovascular events (sudden death, fatal, nonfatal: stroke, myocardial infarction, thromboem- bolic events, coronary revascularisation) as a com- Methods posite end point. Any interaction between risk Criteria for considering studies for this review factors for cardiovascular disease or bleeding, and concomitant treatment were analysed if appropriate (a) Types of studies data were available. Further details will be obtained Single- or double-blind randomised controlled trials from trial authors, if possible. comparing antiplatelet drugs or oral anticoagulation The search strategy for identification of studies is with control or active treatment were included. summarised in Table 1 (also see Collaborative Cohort-studies, nonrandomised controlled studies, Review Group Research Strategy17). and open-label studies were excluded. Methods of the review (b) Types of participants Patients with at least mild hypertension or isolated Two reviewers (GYHL and DCF), independently, systolic or diastolic hypertension as defined (for selected suitable trials for the inclusion of the practical reasons) by the WHO–ISH Guidelines for review. There was a review of the inclusion criteria Management of Hypertension 1999 and/or British for each question, the search strategies, the metho- Society of Hypertension Guidelines for Management dology criteria, and methods for pooling the data. of Hypertension 199914,15 were included. In trials Nonrandomised studies would not usually be help- prior to 1999, WHO–ISH guidelines valid at the time ful in a review of the effects of these drugs as any of the study/publication were used.16 Generally, a estimates of treatment effects are likely to be biased, systolic blood pressure (SBP) of X160 mmHg and/or but they have been included as they may help in a DBP of X100 mmHg
Load more

Recommended publications
  • Aspirin for the Primary Prevention of Cardiovascular Events: a Summary of the Evidence
    Aspirin for the Primary Prevention of Cardiovascular Events: A Summary of the Evidence Michael Hayden, MD; Michael Pignone, MD, MPH; Christopher Phillips, MD; Cynthia Mulrow, MD, MSc Epidemiolgy power to precisely estimate major harms such as gastrointestinal bleeding and hemorrhagic stroke.4,5 Cardiovascular disease (CVD), including ischemic coronary heart disease (CHD), stroke, and The results of these first 2 randomized, controlled peripheral vascular disease, is the leading cause of trials were available to the members of the U.S. morbidity and mortality in the United States.1 In Preventive Services Task Force at the time of their 1997, the age-adjusted mortality rate due to 1996 recommendation.4,5 At that time, the Task coronary heart disease, cerebrovascular disease, and Force found insufficient evidence to recommend for atherosclerotic disease was 194 per 100,000 people, or against routine aspirin prophylaxis for the equating to more than 500,000 deaths per year.1 The primary prevention of myocardial infarction in estimated direct and indirect costs of CHD and asymptomatic people.6 stroke were $145 billion for 1999.2 Two additional large primary prevention trials Although the benefit of aspirin for patients with were published in 1998, and another was reported in known CVD is well established,3 the question of January 2001.7, 8, 9 In light of the new evidence, the whether aspirin reduces the risk of CVD in people U.S. Preventive Services Task Force sought to without known CVD is controversial. Two early reassess the value of aspirin for the primary randomized trials of aspirin in healthy men, the U.S.
    [Show full text]
  • Venous Thromboembolism
    CLINICAL PRACTICE GUIDELINES MOH/P/PAK/264.13(GU) Prevention and Treatment of Venous Thromboembolism VTE Ministry of Health Malaysian Society of National Heart Association Academy of Medicine Malaysia Haematology of Malaysia Malaysia STATEMENT OF INTENT These guidelines are meant to be a guide for clinical practice, based on the best available evidence at the time of development. Adherence to these guidelines may not necessarily ensure the best outcome in every case. Every health care provider is responsible for the management options available locally. REVIEW OF THE GUIDELINES These guidelines were issued in 2013 and will be reviewed in 2017 or sooner if new evidence becomes available. Electronic version available on the following website: http://www.haematology.org.my DISCLOSURE STATEMENT The panel members had completed disclosure forms. None held shares in pharmaceutical firms or acted as consultants to such firms (details are available upon request from the CPG Secretariat). SOURCES OF FUNDING The development of the CPG on Prevention and Treatment of Venous Thromboembolism was supported via unrestricted educational grant from Bayer Healthcare Pharmaceuticals. The funding body has not influenced the development of the guidelines. ISBN 978-967-12100-0-0 9 789671 210000 August 2013 © Ministry of Health Malaysia 01 GUIDELINES DEVELOPMENT The development group for these guidelines consists of Haematologist, Cardiologist, Neurologist, Obstetrician & Gynaecologist, Vascular Surgeon, Orthopaedic Surgeon, Anaesthesiologist, Pharmacologist and Pharmacist from the Ministry of Health Malaysia, Ministry of Higher Education Malaysia and the Private sector. Literature search was carried out at the following electronic databases: International Health Technology Assessment website, PUBMED, MEDLINE, Cochrane Database of Systemic Reviews (CDSR), Journal full teXt via OVID search engine and Science Direct.
    [Show full text]
  • Proefschrift-Banne-Nemeth.Pdf
    Stellingen behorende bij het proefschrift Venous thrombosis following lower-leg cast immobilization and knee arthroscopy From a population-based approach to individualized therapy 1. A prophylactic regimen of low-molecular-weight-heparin for eight days after knee arthroscopy or during the complete immobilization period in patients with casting of the lower leg is not efective for the prevention of symptomatic venous thromboembolism. -this thesis- 2. For patients with a history of venous thromboembolism who are undergoing surgery or are treated with a lower leg cast, the risk of recurrent venous thromboembolism is high. -this thesis- 3. Estimating the risk of venous thromboembolism risk following lower leg cast immobilization or following knee arthroscopy is feasible by using a risk prediction model. -this thesis- 4. A targeted approach, by identifying high-risk patients who may beneft from a higher dose or longer duration of thromboprophylactic therapy, is a promising next step to prevent symptomatic VTE following lower leg cast immobilization or knee arthroscopy. -this thesis- 5. The best treatment strategy to prevent symptomatic venous thromboembolism following lower leg cast immobilization or following knee arthroscopy is yet to be determined. 6. Prognostic models are meant to assist and not to replace clinicians’ decisions. Accurate estimation of risks of outcomes can enhance informed decision making with the patient. -Adapted from PLoS Med 10(2): e1001381- 7. The frst developed prediction model is not the last. 8. Voor de dagelijkse klinische praktijk is het essentieel dat onderzoeksresultaten op de juiste manier worden geïnterpreteerd en toegepast. Om dit te waarborgen is een intensievere samenwerking tussen epidemiologen en dokters aan te raden.
    [Show full text]
  • Anticoagulant Effects of Statins and Their Clinical Implications
    Review Article 1 Anticoagulant effects of statins and their clinical implications Anetta Undas1; Kathleen E. Brummel-Ziedins2; Kenneth G. Mann2 1Institute of Cardiology, Jagiellonian University School of Medicine, and John Paul II Hospital, Krakow, Poland; 2Department of Biochemistry, University of Vermont, Colchester, Vermont, USA Summary cleavage, factor V and factor XIII activation, as well as enhanced en- There is evidence indicating that statins (3-hydroxy-methylglutaryl dothelial thrombomodulin expression, resulting in increased protein C coenzyme A reductase inhibitors) may produce several cholesterol-inde- activation and factor Va inactivation. Observational studies and one ran- pendent antithrombotic effects. In this review, we provide an update on domized trial have shown reduced VTE risk in subjects receiving statins, the current understanding of the interactions between statins and blood although their findings still generate much controversy and suggest that coagulation and their potential relevance to the prevention of venous the most potent statin rosuvastatin exerts the largest effect. thromboembolism (VTE). Anticoagulant properties of statins reported in experimental and clinical studies involve decreased tissue factor ex- Keywords pression resulting in reduced thrombin generation and attenuation of Blood coagulation, statins, tissue factor, thrombin, venous throm- pro-coagulant reactions catalysed by thrombin, such as fibrinogen boembolism Correspondence to: Received: August 30, 2013 Anetta Undas, MD, PhD Accepted after major revision: October 15, 2013 Institute of Cardiology, Jagiellonian University School of Medicine Prepublished online: November 28, 2013 80 Pradnicka St., 31–202 Krakow, Poland doi:10.1160/TH13-08-0720 Tel.: +48 12 6143004, Fax: +48 12 4233900 Thromb Haemost 2014; 111: ■■■ E-mail: [email protected] Introduction Most of these additional statin-mediated actions reported are independent of blood cholesterol reduction.
    [Show full text]
  • Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin
    Thrombosis Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin Guest Editors: Christian Doutremepuich, Jawad fareed, Jeanine M. Walenga, Jean-Marc Orgogozo, and Marie Lordkipanidzé Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin Thrombosis Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin Guest Editors: Christian Doutremepuich, Jawad fareed, Jeanine M. Walenga, Jean-Marc Orgogozo, and Marie Lordkipanidze´ Copyright © 2012 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Thrombosis.” All articles are open access articles distributed under the Creative Commons Attribu- tion License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Louis M. Aledort, USA Thomas Kickler, USA Johannes Oldenburg, Germany David Bergqvist, Sweden S. P. Kunapuli, USA Graham F. Pineo, Canada Francis J. Castellino, USA Jose A. Lopez, USA Domenico Prisco, Italy M. Cattaneo, Italy C. A. Ludlam, Uk Karin Przyklenk, USA Beng Hock Chong, Australia Nageswara Madamanchi, USA Ashwini Koneti Rao, USA Frank C. Church, USA Martyn Mahaut-Smith, UK F. R. Rickles, USA Giovanni de Gaetano, Italy P. M . Ma nnu cc i, Ita ly Evqueni Saenko, USA David H. Farrell, USA Osamu Matsuo, Japan Paolo Simioni, Italy Alessandro Gringeri, Italy Keith R. McCrae, USA C. Arnold
    [Show full text]
  • The Approach to Thrombosis Prevention Across the Spectrum of Philadelphia-Negative Classic Myeloproliferative Neoplasms
    Review The Approach to Thrombosis Prevention across the Spectrum of Philadelphia-Negative Classic Myeloproliferative Neoplasms Steffen Koschmieder Department of Medicine (Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation), Faculty of Medicine, RWTH Aachen University, Pauwelsstr. 30, D-52074 Aachen, Germany; [email protected]; Tel.: +49-241-8080981; Fax: +49-241-8082449 Abstract: Patients with myeloproliferative neoplasm (MPN) are potentially facing diminished life expectancy and decreased quality of life, due to thromboembolic and hemorrhagic complications, progression to myelofibrosis or acute leukemia with ensuing signs of hematopoietic insufficiency, and disturbing symptoms such as pruritus, night sweats, and bone pain. In patients with essential thrombocythemia (ET) or polycythemia vera (PV), current guidelines recommend both primary and secondary measures to prevent thrombosis. These include acetylsalicylic acid (ASA) for patients with intermediate- or high-risk ET and all patients with PV, unless they have contraindications for ASA use, and phlebotomy for all PV patients. A target hematocrit level below 45% is demonstrated to be associated with decreased cardiovascular events in PV. In addition, cytoreductive therapy is shown to reduce the rate of thrombotic complications in high-risk ET and high-risk PV patients. In patients with prefibrotic primary myelofibrosis (pre-PMF), similar measures are recommended as in those with ET. Patients with overt PMF may be at increased risk of bleeding and thus require a more individualized approach to thrombosis prevention. This review summarizes the thrombotic Citation: Koschmieder, S. The risk factors and primary and secondary preventive measures against thrombosis in MPN. Approach to Thrombosis Prevention across the Spectrum of Keywords: myeloproliferative neoplasms (MPN); polycythemia vera (PV); essential thrombocythemia Philadelphia-Negative Classic (ET); primary myelofibrosis (PMF); thrombosis; prevention; antiplatelet agents; anticoagulation; cy- Myeloproliferative Neoplasms.
    [Show full text]
  • Antiplatelets, Anticoagulants and Bleeding Risk and Ppis
    GP INFOSHEET – ANTITHROMBOTICS AND BLEEDING RISK Author(s): Dr. Stuart Rison; Dr. John Robson; Version: 1.6; Last updated 28/11/2019 ANTIPLATELETS, ANTICOAGULANTS AND BLEEDING RISK – WHICH AGENTS AND FOR HOW LONG?; WHY USE PPIs? KEY RECOMMENDATION Patients taking anticoagulants or antiplatelet medicines at high bleed risk should be considered for a Proton Pump Inhibitor (PPI). PPIs reduce bleeding risk by 70% or more. Patients age 65 years or more on anticoagulants or antiplatelet agents are at increased risk because of their age and bleeding risk continues to rise exponentially at older ages. PPIs are recommended in patients on anticoagulants or antiplatelet agents: o At any age with previous GI bleeding o Age 75 years or older o 65 years or older with additional risk factors (see box below) o Interacting medication Dual antiplatelet therapy (DAPT) for cardiac conditions - typically aspirin + clopidogrel - is rarely justified for more than 1 year. Review use for more than one 1 year and in conjunction with the cardiologist consider whether this can revert to a single agent. Dual-pathway therapy for atrial fibrillation - both an anticoagulant and one or more antiplatelet agents- is also rarely justified for longer than 1 year. Consider anticoagulant alone with appropriate specialist advice. ADDITIONAL GI-BLEED RISK FACTORS Anaemia Hb <11g/L Impaired renal function (eGFR<30) Upper GI inflammation (and of course previous GI bleeding) Liver disease Interacting medicines (NSAIDs, SSRI/SNRIs, bisphosphonates, lithium, spironolactone, phenytoin, carbamazepine) WHAT DO WE MEAN BY ANTITHROMBOTICS? Antithrombotics reduce blood clot formation1. There are two main categories: 1. Antiplatelet agent – inhibit platelet aggregation e.g.
    [Show full text]
  • Final Program
    In Memoriam: Final Program XXV Congress of the International Society on Thrombosis and Haemostasis and 61st Annual SSC Meeting June 20 – 25, 2015 Toronto, Canada www.isth2015.org 1 Final Program Table of Contents 3 Venue and Contacts 5 Invitation and Welcome Message 12 ISTH 2015 Committees 24 Congress Support 25 Sponsors and Exhibitors 27 ISTH Awards 32 ISTH Society Information 37 Program Overview 41 Program Day by Day 55 SSC and Educational Program 83 Master Classes and Career Mentorship Sessions 87 Nurses Forum 93 Scientific Program, Monday, June 22 94 Oral Communications 1 102 Plenary Lecture 103 State of the Art Lectures 105 Oral Communications 2 112 Abstract Symposia 120 Poster Session 189 Scientific Program, Tuesday, June 23 190 Oral Communications 3 198 Plenary Lecture 198 State of the Art Lectures 200 Oral Communications 4 208 Plenary Lecture 209 Abstract Symposia 216 Poster Session 285 Scientific Program, Wednesday, June 24 286 Oral Communications 5 294 Plenary Lecture 294 State of the Art Lectures 296 Oral Communications 6 304 Abstract Symposia 311 Poster Session 381 Scientific Program, Thursday, June 25 382 Oral Communications 7 390 Plenary Lecture 390 Abstract Symposia 397 Highlights of ISTH 399 Exhibition Floor Plan 402 Exhibitor List 405 Congress Information 406 Venue Plan 407 Congress Information 417 Social Program 418 Toronto & Canada Information 421 Transportation in Toronto 423 Future ISTH Meetings and Congresses 2 427 Authors Index 1 Thank You to Everyone Who Supported the Venue and Contacts 2014 World Thrombosis Day
    [Show full text]
  • Current Status of Antifibrinolytics in Cardiopulmonary Bypass and Elective Deep Hypothermic Circulatory Arrest Jeffrey A
    Anesthesiology Clin N Am 21 (2003) 527–551 Current status of antifibrinolytics in cardiopulmonary bypass and elective deep hypothermic circulatory arrest Jeffrey A. Green, MD*, Bruce D. Spiess, MD Department of Anesthesiology, Virginia Commonwealth University, Medical College of Virginia Campus, 1200 East Broad Street, PO Box 980695, Richmond, VA 23209 USA Bleeding after cardiopulmonary bypass Cardiopulmonary bypass (CPB) alters the hemostatic balance and predisposes cardiac surgery patients to an increased risk of microvascular bleeding. Bleeding and the need for transfusion are among the most common complications of cardiac surgery. In fact, until recently, blood transfusions seemed to be required for about 50% of all cardiac surgery patients [1]. Currently, CPB accounts for 10% to 20% of the transfusions performed in the United States [2,3]. Transfusion, however, exposes patients to added risks such as infectious disease transmission [4], transfusion reactions [5], graft-versus-host disease [6], transfusion-induced lung injury [7], and decreased resistance to postoperative infection [8,9]. Transfusion increases the risk of infection by 35% to 300% and increases the risk of pneumonia in coronary artery bypass (CABG) patients by 5% per unit transfused [10]. The primary purported benefit of transfusion, increased oxygen carrying capacity, has not been definitively proven. Excessive postoperative bleeding may necessitate surgical reexploration, increasing morbidity, and mortality. Postoperatively, the risk of excessive bleeding is 11% [11], and 5% to 7% of patients lose more than 2 L of blood in the first 24 hours after CPB [12]. Reexploration for hemorrhage is required in 3.6% to 4.2% of patients [13], and mortality rates range from 10% to 22% [14].
    [Show full text]
  • A First in Class Treatment for Thrombosis Prevention. a Phase I
    Journal of Cardiology and Vascular Medicine Research Open Access A First in Class Treatment for Thrombosis Prevention. A Phase I study with CS1, a New Controlled Release Formulation of Sodium Valproate 1,2* 2 3 2 1,2 Niklas Bergh , Jan-Peter Idström , Henri Hansson , Jonas Faijerson-Säljö , Björn Dahlöf 1Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 2 Cereno Scientific AB, Gothenburg, Sweden 3 Galenica AB, Malmö, Sweden *Corresponding author: Niklas Bergh, The Wallenberg Laboratory for Cardiovascular Research Sahlgrenska University Hospi- tal Bruna Stråket 16, 413 45 Göteborg, Tel: +46 31 3421000; E-Mail: [email protected] Received Date: June 11, 2019 Accepted Date: July 25, 2019 Published Date: July 27, 2019 Citation: Niklas Bergh (2019) A First in Class Treatment for Thrombosis Prevention? A Phase I Study With Cs1, a New Con- trolled Release Formulation of Sodium Valproate. J Cardio Vasc Med 5: 1-12. Abstract Several lines of evidence indicate that improving fibrinolysis by valproic acid may be a fruitful strategy for throm- bosis prevention. This study investigated the safety, pharmacokinetics, and effect on biomarkers for thrombosis of CS1, a new advanced controlled release formulation of sodium valproate designed to produce optimum valproic acid concen- trations during the early morning hours, when concentrations of plasminogen activator inhibitor (PAI)-1 and the risk of thrombotic events is highest. Healthy volunteers (n=17) aged 40-65 years were randomized to receive single doses of one of three formulations of CS1 (FI, FII, and FIII). The CS1 FII formulation showed the most favorable pharmacokinetics and was chosen for multiple dosing.
    [Show full text]
  • Antithrombotic Therapy for VTE Disease, 10Th Ed, 2016
    [ Evidence-Based Medicine ] Antithrombotic Therapy for VTE Disease CHEST Guideline and Expert Panel Report Clive Kearon, MD, PhD; Elie A. Akl, MD, MPH, PhD; Joseph Ornelas, PhD; Allen Blaivas, DO, FCCP; David Jimenez, MD, PhD, FCCP; Henri Bounameaux, MD; Menno Huisman, MD, PhD; Christopher S. King, MD, FCCP; Timothy A. Morris, MD, FCCP; Namita Sood, MD, FCCP; Scott M. Stevens, MD; Janine R. E. Vintch, MD, FCCP; Philip Wells, MD; Scott C. Woller, MD; and COL Lisa Moores, MD, FCCP BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics. METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence. RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C).
    [Show full text]
  • State-Of-The-Art Thrombosis Prevention and Treatment
    FOREWORD State-of-the-art thrombosis prevention and treatment antagonists are used for longer periods of primary ‘Pulmonary embolism is a and secondary prophylaxis of thrombosis. leading cause of death in Heparins, especially unfractionated, have draw- cancer patients and the risk for backs, including the need for subcutaneous venous thromboembolism is injections and the risk for heparin-induced thrombocytopenia and osteoporosis on long- significantly increased in patients term use. The heparin derivatives requires bind- with solid tumors and ing to antithrombin in order to exert their anti- hematological malignancies.’ coagulant properties. Vitamin K antagonists have a narrow thera- Benjamin Brenner Thrombosis is the leading cause of death in peutic range that necessitates frequent monitoring Rambam Health Care developed countries, with arterial thrombosis of the prothrombin time. The pharmacogenetics Campus, Department of presenting as myocardial infarction, stroke or of the vitamin K epoxide reductase and CYP219 Hematology and Bone Marrow Transplantation, peripheral arterial occlusion. Venous thrombo- genes may be helpful to better define the dose and Haifa, Israel embolism (VTE) is a major cause of mortality the risk for bleeding on vitamin K antagonists [5]. Tel.: +972 4854 3520 worldwide, despite some variations in prevalence These limitations led to the development of Fax: +972 4854 3886 of the disease [1]. While the incidence of VTE numerous new antithrombotic agents during the E-mail: b_brenner@ rambam.health.gov.il increases with aging, it is the leading cause of past decade, and to an ongoing effort by the vascular morbidity in young adults. industry to develop novel anticoagulants with A multitude of risk factors can contribute to improved efficacy and safety profile and better presentation of VTE [2].
    [Show full text]