DOCSLIB.ORG

Dual Antithrombotic Therapy in Chronic Coronary Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dual Antithrombotic Therapy in Chronic Coronary Syndrome Editorial to prescribe more potent agents but may Heart: first published as 10.1136/heartjnl-2021-319830 on 12 August 2021. Downloaded from Adding to the evidence or to the have feared a higher bleeding risk with prasugrel or ticagrelor. confusion: dual antithrombotic therapy Interestingly, the authors report no difference in major bleeding between in chronic coronary syndrome and both cohorts (2.35% vs 2.95%, p=0.456) which again contrasts with atrial fibrillation the findings of HOST- EXAM where clopidogrel was associated not only with Shinwan Kany , Renate Schnabel fewer thrombotic events (3.7% vs 5.5%, p=0.003) but also less bleeding (2.3% vs 3.3%, p=0.003).7 The pathophysio- Atrial fibrillation (AF) is the most common Patients in the dual antithrombotic logical background of aspirin- induced arrhythmia in the world with the lifetime arm were compared in regard to addi- gastric bleeding is nicely explained by risk estimated to be 1/3 in men and women tional APT (P2Y inhibitors n=297 vs 12 the inhibition of cyclo- oxygenase which over the age of 50 years.1 Cardiovascular aspirin n=778) and a primary outcome of not only leads to the desired inhibition disease, like misfortune, does not come composite of stroke, systemic embolism, of platelet- aggregator thromboxane A singly in most cases. Coronary artery myocardial infarction, unstable angina 2 but also the synthesis of prostaglandins disease (CAD) with the chronic coronary requiring urgent revascularisation or syndrome (CCS) or acute coronary death from any cause. No difference in the which are essential for gastric mucus syndrome (ACS) is a common comorbid primary outcome was observed in patients secretion (figure 1). condition. Management of patients with One of the strengths in the work by receiving P2Y12 inhibitors or aspirin AF with a comprehensive treatment of risk (6.76% vs 5.28%, p=0.178). However, Fukaya et al may be the utilisation of factors and concomitant diseases is the key proton pump inhibitors (PPIs) in both mortality was higher in the P2Y12 inhibi- to treat these patients. Yet, the devil is in tors group (4.44% vs 2.85% per patient- cohorts (64.3% in the P2Y12 group and the details as treatment becomes increas- year; p=0.041). 62% in the aspirin group). In the ‘Rivar- ingly complex. There is limited evidence in the compar- oxaban for the Prevention of Major Patients with AF and CAD require anti- Cardiovascular Events in Coronary or ison of aspirin with P2Y12 inhibitors in platelet therapy (APT) in addition to oral addition to OAC in patients with CCS. Peripheral Artery Disease (COMPASS)’ anticoagulation (OAC) after myocardial The AFIRE main trial showed that these trial where rivaroxaban 2.5 mg daily in infarction or percutaneous coronary inter- patients do not benefit from additional addition to aspirin in stable atheroscle- vention (PCI) for a limited time period. APT,5 but doubts remain, and dual anti- rotic disease was shown to reduce cardio- Depending on ischaemic risk, bleeding thrombotic therapy is still common in vascular mortality, an interesting substudy risk and unplanned PCI, different treat- 6 clinical practice. The benefit seen with was conducted. Patients who were not on ment regimens are available with dual http://heart.bmj.com/ clopidogrel compared with aspirin in PPI at baseline were randomised to PPI antithrombotic therapy with OAC and the monotherapy of patients undergoing or placebo resulting in two groups over APT up to 12 months.2 Looking at PCI, recently shown with the ‘Harmo- 8000 patients with a mean follow-up of each possible combination of drugs and nizing Optimal Strategy for Treatment of therapy length, the cardiologist is left with 3 years. Therapy with PPI was shown to Coronary Artery Stenosis-EXtended Anti- 2.8 million possible combinations in the be very safe without increase in cardio- platelet Monotherapy (HOST-EX AM)’ first 12 months only.3 vascular events, cancer or pneumonia trial, is not evident in patients with AF in or dementia but a twofold increase of 4 on September 26, 2021 by guest. Protected copyright. the analysis by Fukaya et al. Clostridium difficile infections.8 The PRECISION MEDICINE BUT TOO MANY Interpretation of this data is to be seen COGENT trial showed that concomitant OPTIONS WITH LOW EVIDENCE? in the contexts of its many caveats. The therapy with PPI (in this case omeprazole) This subanalysis from the recently AFIRE trial was randomised, but the in patients with APT reduces gastrointes- published randomised controlled ‘Atrial comparison of P2Y inhibitors and aspirin 12 tinal bleeding without a rise in thrombotic Fibrillation and Ischemic Events With was not, as seen with significant base- events.9 However, the most recent Euro- Rivaroxaban in Patients With Stable Coro- line differences between the groups. The pean Society of Cardiology (ESC) guide- nary Artery Disease Study’ (AFIRE) by design was open label, which certainly 4 lines for management of ACS without Fukaya et al examines whether aspirin or can introduce bias. Also, the general- ST- segment elevation (NSTEMI) do not P2Y12 inhibitors (clopidogrel in 94.6%) in isability of the cohorts to European/ addition to rivaroxaban impacts outcomes Western patients is limited. In particular, recommend omeprazole due to concerns in patients with CCS. The main trial of inhibition of CYP2C19 and thus effi- anticoagulant dosing is different here and 2 showed that dual antithrombotic therapy significant numbers of patients received cacy of clopidogrel. is associated with increased mortality bare- metal stents (more than 30% in the The ESC guidelines on management of compared with OAC monotherapy in aspirin group) which is not standard of AF mention PPIs without giving a level patients with AF and CCS. care anymore in the guidelines. General of recommendation akin to the NSTEMI guidelines. With the abundance of data assumptions on P2Y12 inhibitors should supporting the use of PPI in patients Cardiology, University Heart and Vascular Centre be avoided, since almost 95% of patients with antiplatelet or dual antithrombotic Hamburg- Eppendorf, Hamburg, Germany with P2Y12 inhibitors received clopidogrel instead of more potent antiplatelet drugs therapy, they should be considered more Correspondence to Dr Shinwan Kany, Cardiology, University Medical Center Hamburg- Eppendorf, like prasugrel or ticagrelor. Prescribing frequently and guidelines have to provide Hamburg 20246, Germany; s. kany@ uke. de physicians in the AFIRE trial were free more powerful recommendation. Kany S, Schnabel R. Heart Month 2021 Vol 0 No 0 1 Editorial Non Commercial (CC BY- NC 4.0) license, which permits Heart: first published as 10.1136/heartjnl-2021-319830 on 12 August 2021. Downloaded from others to distribute, remix, adapt, build upon this work non- commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non- commercial. See: http:// creativecommons.org/ licenses/ by- nc/ 4. 0/. © Author(s) (or their employer(s)) 2021. Re- use permitted under CC BY- NC. No commercial re- use. See rights and permissions. Published by BMJ. To cite Kany S, Schnabel R. Heart Epub ahead of print: [please include Day Month Year]. doi:10.1136/ heartjnl-2021-319830 http:// dx. doi. org/ 10. 1136/ heartjnl- 2021- 319321 Figure 1 Overview about antiplatelet and anticoagulation mechanisms on haemostasis ► to prevent thrombotic events while increasing bleeding risk. In patients with AF and CCS, Heart 2021;0:1–2. doi:10.1136/heartjnl-2021-319830 antithrombotic drugs can be either antiplatelet drugs or oral anticoagulation (OAC). Aspirin and P2Y12 lead to an inhibition of glycoprotein IIb/IIIa, a fibrinogen receptor that aids platelet ORCID iDs Shinwan Kany http:// orcid. org/ 0000- 0001- 8113- 733X activation. Aspirin blocks the formation of thromboxane A2 (TXA2) limiting platelet aggregation and also reduces gastric mucus secretion. OAC either inhibits factor Xa (FXa) or thrombin to reduce Renate Schnabel http:// orcid. org/ 0000- 0001- 7170- 9509 clotting formation. Both medications reduce thrombotic events such as ischaemic stroke (mainly OAC) and coronary ischaemic events (antiplatelets) but increase bleeding risk, that is, gastric bleeding. Potential protection may arise from proton pump inhibitors (PPIs) and histamine H2 REFERENCES 1 Magnussen C, Niiranen TJ, Ojeda FM, et al. Sex receptor (H2 blockers) may provide protection by reducing stomach acid production. Adapted from 2 differences and similarities in atrial fibrillation Collet et al. AF, atrial fibrillation; CCS, chronic coronary syndrome. epidemiology, risk factors, and mortality in community cohorts: results from the BiomarCaRE Consortium (biomarker for cardiovascular risk assessment in CONCLUSION The personalised treatment of patients Europe). Circulation 2017;136:1588–97. In conclusion, the authors shed some new with concomitant AF and CCS remains 2 Collet J- P, Thiele H, Barbato E, et al. 2020 ESC light on the dual antithrombotic therapy complex and more evidence is required to guidelines for the management of acute coronary syndromes in patients presenting without persistent of patients with AF and concomitant CCS. make guideline recommendations. ST- segment elevation. Eur Heart J 2021;42:1289–367. http://heart.bmj.com/ While not recommended without acute 3 Gibson CM. Going polymer free and dual antiplatelet Twitter Shinwan Kany @kany_md coronary events and certainly related to free earlier. J Am Coll Cardiol 2017;69:172–5. an increased risk of bleeding, it represents Contributors SK wrote the initial draft of the 4 Fukaya H, Ako J, Yasuda S, et al. Aspirin versus manuscript. SK and RS worked on the figure and the P2Y12 inhibitors with anticoagulation therapy the clinical reality in many cases. Whereas final manuscript. for atrial fibrillation. Heart 2021. doi:10.1136/ heartjnl-2021-319321. [Epub ahead of print: 14 Jul the current study suggests that aspirin or Funding The authors have not declared a specific 2021].
Load more

Recommended publications
  • 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]
  • 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]
  • 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]
  • 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]
  • AHFS Pharmacologic-Therapeutic Classification (2012).Pdf
    AHFS Pharmacologic-Therapeutic Classification 4:00 Antihistamine Drugs 4:04 First Generation Antihistamines 4:04.04 Ethanolamine Derivatives 4:04.08 Ethylenediamine Derivatives 4:04.12 Phenothiazine Derivatives 4:04.16 Piperazine Derivatives 4:04.20 Propylamine Derivatives 4:04.92 Miscellaneous Derivatives 4:08 Second Generation Antihistamines 4:92 Other Antihistamines* 8:00 Anti-infective Agents 8:08 Anthelmintics 8:12 Antibacterials 8:12.02 Aminoglycosides 8:12.06 Cephalosporins 8:12.06.04 First Generation Cephalosporins 8:12.06.08 Second Generation Cephalosporins 8:12.06.12 Third Generation Cephalosporins 8:12.06.16 Fourth Generation Cephalosporins 8:12.07 Miscellaneous -Lactams 8:12.07.04 Carbacephems 8:12.07.08 Carbapenems 8:12.07.12 Cephamycins 8:12.07.16 Monobactams 8:12.08 Chloramphenicol 8:12.12 Macrolides 8:12.12.04 Erythromycins 8:12.12.12 Ketolides 8:12.12.92 Other Macrolides 8:12.16 Penicillins 8:12.16.04 Natural Penicillins 8:12.16.08 Aminopenicillins 8:12.16.12 Penicillinase-resistant Penicillins 8:12.16.16 Extended-spectrum Penicillins 8:12.18 Quinolones 8:12.20 Sulfonamides 8:12.24 Tetracyclines 8:12.24.12 Glycylcyclines 8:12.28 Antibacterials, Miscellaneous 8:12.28.04 Aminocyclitols 8:12.28.08 Bacitracins 8:12.28.12 Cyclic Lipopeptides 8:12.28.16 Glycopeptides 8:12.28.20 Lincomycins 8:12.28.24 Oxazolidinones 8:12.28.28 Polymyxins 8:12.28.30 Rifamycins 8:12.28.32 Streptogramins 8:12.28.92 Other Miscellaneous Antibacterials* 8:14 Antifungals 8:14.04 Allylamines 8:14.08 Azoles 8:14.16 Echinocandins 8:14.28 Polyenes 8:14.32
    [Show 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.
    [Show full text]
  • Use of Antithrombotic Medications in the Presence of Neuraxial Anesthesia
    Guideline: Use of Antithrombotic Medications In The Presence of Neuraxial Anesthesia Use of Antithrombotic Medications In The Presence of Neuraxial Anesthesia Purpose of Guidelines: To establish appropriate administration and timing of antithrombotic medications before, during, and after the use of neuraxial anesthesia to minimize the risk of bleeding. Definitions: Neuraxial Anesthesia = Delivery of anesthetic medication requiring placement of catheters or needles into the epidural or spinal space Antithrombotic Medications = Anticoagulant, antiplatelet, and thrombolytic medications Background1-3: Spinal (or epidural) hematomas are a rare but catastrophic complication of neuraxial anesthesia. The risk of hematoma development is increased in the presence of antithrombotic medication. Patients undergoing neuraxial anesthesia must have the risks of bleeding from neuraxial interventions balanced with the underlying and ongoing risk of thromboembolism necessitating anticoagulation. Recommendations for the management of specific antithrombotics in patients undergoing neuraxial anesthesia are provided in the following Tables: o Table 1. Management of Intravenous and Subcutaneous Anticoagulation Therapy in Patients Undergoing Neuraxial Anesthesia o Table 2. Management of ORAL Anticoagulation Therapy in Patients Undergoing Neuraxial Anesthesia o Table 3. Management of ORAL and Intravenous Antiplatelet and Thrombolytic Therapy in Patients Undergoing Neuraxial Anesthesia Workflow if a Contradicted Medication is Prescribed: Providers will have
    [Show full text]
  • Online Appendix
    The More We Die, The More We Sell? A Simple Test of the Home-Market Effect Online Appendix Arnaud Costinot Dave Donaldson MIT, CEPR, and NBER MIT, CEPR, and NBER Margaret Kyle Heidi Williams Mines ParisTech and CEPR MIT and NBER December 28, 2018 1 Contents A Theoretical Appendix3 A.1 Multinational Enterprises (Section III.1)..........................3 A.2 Log-Linearization (Section III.2)...............................3 A.3 Beyond Perfect Competition (Section III.3).........................6 A.3.1 Monopolistic Competition..............................6 A.3.2 Variable Markups...................................7 A.3.3 Endogenous Innovation...............................8 A.3.4 Price Regulations...................................9 A.4 Bilateral Sales (Section VI.1)................................. 12 B Empirical Appendix 12 B.1 Rich versus Poor Countries................................. 12 B.2 Additional Empirical Results................................ 13 B.3 Benchmarking IMS MIDAS data.............................. 13 B.3.1 Benchmarking to the OECD HealthStat Data................... 13 B.3.2 Benchmarking to the MEPS Data.......................... 14 B.4 ATC to GBD Mapping.................................... 15 2 A Theoretical Appendix A.1 Multinational Enterprises (Section III.1) In this appendix, we illustrate how to incorporate multinational production into our basic envi- ronment. Following Ramondo and Rodríguez-Clare(2013), suppose that each firm headquartered in country i that sells drugs targeting disease n in country j 6= i can choose the country l in which its production takes place. If l = i, then the firm exports, if l = j, it engages in horizontal FDI, and if l 6= i, j, it engages in platform FDI. Like in Ramondo and Rodríguez-Clare(2013), we assume that firm-level production functions exhibit constant returns to scale, but we further allow for external economies of scale at the level of the headquarter country for each disease.
    [Show full text]
  • GUIDELINE for ANTITHROMBOTIC REVERSAL Table 1
    GUIDELINE for ANTITHROMBOTIC REVERSAL This document is intended as a guideline only and should not replace sound clinical judgment Table 1: Reversal for ANTICOAGULANT therapy ANTITHROMBOTIC REVERSAL AGENT COMMENTS DIRECT THROMBIN Short half-life and discontinuation of DTI are primary means of attenuating bleed – Off-label use of INHIBITORS (DTIs) rFVIIa/PCC: support with crystalloid and blood products to facilitate rapid renal clearance of drug – REQUIRES ATTENDING IV: 4 Factor PCC APPROVAL – Argatroban Dose*: 50 units/kg (dose cap at 100 kg to mitigate thrombotic risk) – Document attending – Bivalirudin Administration: Place in empty IV bag and give slow IV push over 10 minutes name in the order (Angiomax®) • Use within 4 hours of reconstitution comments Half-life 10-90 Onset: <30 minutes minutes Caution: thrombotic risk Additional options: PO: – If dabigatran ingested – Dabigatran within 1 hour, consider (Pradaxa®) rFVIIa activated charcoal. Dose*: 100 mcg/kg (dose cap at 100 kg to mitigate thrombotic risk) Half-life 12-17 – Mechanical methods, • May repeat in 2 hours if continued bleeding hours in normal such as dialysis, may be Administration: IV bolus over 3-5 minutes renal function considered as a last • Use within 3 hours of reconstitution resort The aPTT is currently Onset: <30 minutes Caution: thrombotic risk the only readily Recommend not giving available lab test to rFVIIa and PCC together QUALITATIVELY due to high risk of measure dabigatran. thrombosis unless clinical Do not use PT/INR situation warrants FACTOR XA 4 Factor
    [Show full text]
  • Antiplatelet Agents Vs. Anticoagulation for Stroke & Tia
    ANTIPLATELET AGENTS VS. ANTICOAGULATION FOR STROKE & TIA David Lee Gordon, M.D., FAAN, FANA, FAHA Professor and Chair Department of Neurology The University of Oklahoma Health Sciences Center OU Neurology ANTIPLATELET AGENTS VS. ANTICOAGULATION FOR STROKE & TIA Learning Objectives . Describe the two main ways that blood clots using nonmedical terms . List the 6 ischemic stroke etiologies . Determine the optimal antithrombotic therapy for secondary prevention of ischemic stroke based on ischemic stroke etiology . Relate the rationale for prescribing anticoagulation rather than antiplatelet agents in patients with ischemic stroke of unknown cause OU Neurology THE BLOOD Unique substance that fluctuates between two forms . Liquid –to transport blood cells, oxygen, glucose, other chemistries, etc. within the vascular system . Glue – to seal injured artery or vein & prevent blood loss – Scab & clot (= thrombus) are examples of blood as glue – Glue (scab/clot) forms for 1 of 2 reasons: • Platelets (white clot) – like Velcro – Stick to bumpy surfaces inside arteries – If the inner lining of the artery (endothelium) is normal, platelets do NOT cause thrombus formation • Clotting factors (red clot) – like powdered Jello – Exist in balance with natural blood thinners – Clump when blood is stagnant or when unopposed by natural blood thinners OU Neurology BLOOD‐THINNING THERAPY . Antithrombotic therapy is a general term for all blood‐thinning medications . There are 2 types of antithrombotic therapy – Antiplatelet agents –anti‐Velcro medicines – Anticoagulants –anti‐Jello medicines OU Neurology ISCHEMIC STROKE & TIA PATHOPHYSIOLOGY Ischemia (low blood flow) to focal area of brain . Usually due to thromboembolus (floating blood clot) – Thrombus = blood clot – Embolus = floating plug – Blood clot forms in vascular system (arteries or heart), travels downstream, plugs a brain artery .
    [Show full text]
  • A Specific Antidote for Reversal of Anticoagulation by Direct and Indirect Inhibitors of Coagulation Factor Xa
    ARTICLES A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa Genmin Lu1, Francis R DeGuzman2, Stanley J Hollenbach2, Mark J Karbarz1, Keith Abe2, Gail Lee2, Peng Luan1, Athiwat Hutchaleelaha3, Mayuko Inagaki3, Pamela B Conley1, David R Phillips1 & Uma Sinha1 Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding. We designed and expressed a modified form of fXa as an antidote for fXa inhibitors. This recombinant protein (r-Antidote, PRT064445) is catalytically inactive and lacks the membrane-binding g-carboxyglutamic acid domain of native fXa but retains the ability of native fXa to bind direct fXa inhibitors as well as low molecular weight heparin– activated antithrombin III (ATIII). r-Antidote dose-dependently reversed the inhibition of fXa by direct fXa inhibitors and corrected the prolongation of ex vivo clotting times by such inhibitors. In rabbits treated with the direct fXa inhibitor rivaroxaban, r-Antidote restored hemostasis in a liver laceration model. The effect of r-Antidote was mediated by reducing plasma anti-fXa activity and the non–protein bound fraction of the fXa inhibitor in plasma. In rats, r-Antidote administration dose-dependently and completely corrected increases in blood loss resulting from ATIII-dependent anticoagulation by enoxaparin or fondaparinux. r-Antidote has the potential to be used as a universal antidote for a broad range of fXa inhibitors. Warfarin, a vitamin K antagonist, is widely used as an anticoagulant As direct oral fXa inhibitors such as rivaroxaban and apixaban have for the prevention and treatment of thrombotic diseases.
    [Show full text]
  • Benefits and Risks of Antithrombotic Therapy for Cardiovascular Disease Prevention
    2019 Scientific Conference Benefits and Risks of Antithrombotic Therapy for Cardiovascular Disease Prevention Friday 28th June 2019 - 8.30 am - 5.10 pm Donna Camilla Savelli Hotel, Via Garibaldi, 27 - 00153 Rome Increasing the knowledge & understanding of Aspirin Page 2 2019 Scientific Conference Benefits and Risks of Antithrombotic Therapy for Cardiovascular Disease Prevention Welcome The International Aspirin Foundation welcomes you to our 29th Scientific Conference in Rome. These are busy and exciting times at the International Aspirin will have saved worldwide is incalculable’. Aspirin Foundation as trial results and clinical debate continue to keep aspirin activity high within scientific, The inaugural chair of the Scientific Advisory Board, medical and research communities. Professor Peter Elwood FRCP OBE, worked with Nick from the early days and next week in London we are As a result, our Scientific Advisory Board, chaired by launching a commemorative issue of his book; ‘Aspirin Professor Carlo Patrono MD FESC, have worked hard to yesterday, aspirin today, aspirin tomorrow: a history create a stimulating programme that delves into some of prophylactic aspirin’. The foreward to this book was of the questions we need to answer and helps achieve written by the late Nick Henderson, where he wrote; The Foundation’s aim of facilitating discussion amongst professionals from a variety of disciplines regarding “My hope is that this publication will also encourage aspirin’s potential in modern medicine. medical professionals to remain passionate about this compound and continue to put effort into researching new Delegates will be pleased to know that this meeting has applications for it in medicine.” been independently accredited by The CPD Standards Office.
    [Show full text]