The Efficacy and Safety of Combination Glycoprotein Iibiiia Inhibitors And

Total Page:16

File Type:pdf, Size:1020Kb

The Efficacy and Safety of Combination Glycoprotein Iibiiia Inhibitors And Interventional Cardiology The efficacy and safety of combination glycoprotein IIbIIIa inhibitors and reduced-dose thrombolytic therapy–facilitated percutaneous coronary intervention for ST-elevation myocardial infarction: A meta-analysis of randomized clinical trials Mohamad C.N. Sinno, MD, Sanjaya Khanal, MD, FACC, Mouaz H. Al-Mallah, MD, Muhammad Arida, MD, and W. Douglas Weaver, MD Detroit, MI Objective We reviewed the literature and performed a meta-analysis comparing the safety and efficacy of adjunctive use of reduced-dose thrombolytics and glycoprotein (Gp) IIbIIIa inhibitors to the sole use of Gp IIbIIIa inhibitors before percutaneous coronary intervention (PCI) in patients presenting with acute ST-segment elevation myocardial infarction (STEMI). Background Early reperfusion in STEMI is associated with improved outcomes. The use of reduced-dose thrombolytic and Gp IIbIIIa inhibitors combination before PCI in the setting of acute STEMI remains controversial. Methods We performed a literature search and identified randomized trials comparing the use of combination therapy–facilitated PCI versus PCI done with Gp IIbIIIa inhibitor alone. Included studies were reviewed to determine Thrombolysis in Myocardial Infarction (TIMI)-3 flow at baseline, major bleeding, 30-day mortality, TIMI-3 flow after PCI,and 30-day reinfarction. We performed a random-effect model meta-analysis. We quantified heterogeneity between studies with I2. A value N50% represents substantial heterogeneity. Results We identified 4 clinical trials randomizing 725 patients; 424 patients were pretreated with combination therapy before PCI, and 301 patients had Gp IIbIIIa inhibitor alone during PCI. Combination therapy–facilitated PCI was associated with a 2-fold increase in TIMI-3 flow upon arrival to the catheterization laboratory compared with the sole use of upstream Gp IIbIIIa inhibitors (192/390 patients [49%] versus 60/284 [21%]; relative risk [RR], 2.2; P b .00001). However, post-PCI TIMI-3 flow was similar between the 2 groups (279/319 patients [87%] versus 188/212 [88%]; RR, 0.99; P = .85). Major bleeding events significantly increased in the combination therapy group (40/420 patients [9.5%] versus 14/299 [4.7%]; RR, 2.2; P = .007). The 30-day mortality (15/424 patients [3.5%] versus 5/301 [1.7%]; RR, 1.47; P = .46) and 30-day reinfarction rate (5/424 patients [1.1%] versus 3/301 [1.0%]; RR, 0.96; P = .96) were similar in the 2 treatment groups. Conclusions Awaiting the results of the ongoing clinical trials, the current cumulative evidence does not support the routine use of combination of reduced-dose thrombolytic and Gp IIbIIIa inhibitor therapy–facilitated PCI for the treatment of STEMI. (Am Heart J 2007;153:579286.) The primary goal of therapy for acute ST-segment artery (IRA) blood flow. Irrespective of whether a elevation myocardial infarction (STEMI) is early, rapid, mechanical versus pharmacological strategy is used, complete, and sustained restoration of infarct-related Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the culprit artery within 90 minutes of presentation has been shown to correlate with im- From the Henry Ford Health System, Detroit, MI. proved 30-day1 and long-term2 survival in patients with Submitted June 20, 2006; accepted December 26, 2006. Reprint requests: Sanjaya Khanal, MD, FACC, Heart Center of Antelope Valley, 43807 acute STEMI. North 10th Street West, Lancaster, CA 93536. Primary percutaneous coronary intervention (PCI) is E-mail: [email protected] currently the preferred approach to reperfusion therapy 0002-8703/$ - see front matter n 2007, Published by Mosby, Inc. when delivered expeditiously in centers with docu- 3 doi:10.1016/j.ahj.2006.12.024 mented expertise and outcomes. Time to treatment, American Heart Journal 580 Sinno et al April 2007 Table I. Summary of characteristics in trials comparing simultaneous use of thrombolytics and glycoprotein IIb/IIIa inhibitors vs glycoprotein IIb/IIIa Inhibitors alone for PCI No. of females/ Symptom onset No. of Patients Total (%) Mean Age yrs. to drug, mins. Combination IIb/IIIa Combination IIb/IIIa Combination IIb/IIIa Combination IIb/IIIa Inclusion therapy inhibitors therapy inhibitors therapy inhibitors therapy inhibitors Study Criteria group group group group group group group group ADVANCE-MI STEMI b6hrs. 74 74 24/148 (16) 28/148 (19) 58 55 - - SPEED STEMI b12hrs. 191 63 49/254 (19) 21/254 (8) 59 57 153 138 BRAVE STEMI b12hrs. 125 128 28/253 (11) 33/253 (13) 63.1 62.3 160 164 APAMIT STEMI b6hrs. 34 36 8/70 (11) 6/70 (9) 55 56 205 259 however, remains an important determinant of clinical PCI, the range of initial pharmacotherapy encompasses outcome in patients with acute STEMI. thrombolytic and glycoprotein (Gp) IIbIIIa inhibitors. Despite the better outcomes, primary PCI has not The use of Gp IIbIIIa inhibitors has been shown to become the treatment of choice for most patients with improve short-term outcomes in most studies of primary STEMI because of logistical issues and the limited PCI.8,9 However, full-dose fibrinolysis-facilitated PCI has availability of institutions that can offer this treatment recently been shown to result in worse outcome than modality in a timely and efficient manner. In the current primary PCI alone.10 The results with combination of US practice, only 4.2% of transferred patients with acute reduced-dose thrombolytic and Gp IIbIIIa inhibitors STEMI were treated within 90 minutes in the National before PCI in patients with MI are however not clear. A Registry of Myocardial Infarction 3/4 registry.4 The idea recent meta-analysis comparing primary and multiple of prehospital ambulance triage of patients with STEMI regimens of thrombolytic-facilitated PCI for STEMI to PCI hospitals has been suggested to decrease inherent showed a higher TIMI grade 3 flow on initial angiogra- time delay that ensues when these patients are seen in phy, but this translated into higher major bleeding non-PCI hospitals. Nallamothu et al5 obtained PCI status events, increased mortality, nonfatal reinfarction, urgent of hospitals from the American Hospital Association target revascularization, and stroke11 compared with annual survey and established the location of the primary PCI alone. This study, however, does not population from the 2000 US census and found that 79% provide guidance about the common practice of the use of the adult population lived within 60 minutes of a PCI of reduced-dose fibrinolytic and Gp IIbIIIa inhibitors hospital. Among those with non-PCI hospitals as the before PCI in patients with acute STEMI. We performed closest facility, the additional time to arrive to a PCI a meta-analysis of randomized clinical trials12-15 testing hospital was 30 minutes.5,6 However, with the variability the safety and efficacy of combination therapy (reduced- of the emergency medical system in the United States, dose thrombolytic + Gp IIbIIIa inhibitors)–facilitated PCI getting electrocardiograms in the ambulance for patients versus PCI performed only with Gp IIbIIIa inhibitors. with chest pain and training paramedics to interpret these electrocardiograms is the major issue. Pharmaco- Methods logical therapy, however, can be carried out expedi- tiously and without site-specific variations in outcome in Study objectives and design patients with STEMI.7 Therefore, it is logical to think that Our primary aim was to compare simultaneous administra- tion of Gp IIbIIIa inhibitors and reduced-dose fibrinolytics initial early pharmacological therapy followed by PCI before PCI to primary PCI done with Gp IIbIIIa inhibitors in may deliver both expediency and efficacy that is desired patients with STEMI. ST-segment elevation myocardial infarc- in treating myocardial infarction (MI) patients. tion was defined according to the inclusion criteria of the In fact, many institutions have current policies of trials concerned. providing initial primary PCI alone, thrombolytic thera- py alone, or combination therapy followed by PCI based Search strategy on estimated time to treatment. In addition to standard All randomized, controlled trials comparing facilitated PCI to therapy of aspirin, heparin, clopidogrel during primary primary angioplasty were identified using a 2-level search American Heart Journal Sinno et al 581 Volume 153, Number 4 trials were also excluded. Outcome data had to be available on culprit artery patency evaluated on admission by TIMI flow grades, bleeding, and mortality. Two authors (M.S., M.M.) independently reviewed abstracts or complete articles. Only Combined 4 nonoverlapping studies met the inclusion criteria. Two Clinical End reviewers performed independent data extraction; all discrep- Trial Angiographic Point (Time to ancies were identified and resolved by consensus or, as Agents eight % End Points Follow up) needed, with a third investigator and confirmed by consensus. Tenecteplase, 20 TIMI 3 Death, Reinfarction Eptifibatide flow grade or new CHF End points and definitions @ 30 days Reteplase, 35 TIMI 3 Death, Reinfarction The primary angiographic end point was TIMI flow grade 3 Abciximab flow grade or urgent on the first angiogram, which defined open culprit artery on Revascularization admission. The TIMI grade 3 flow was also assessed after PCI. @ 30 days Reteplase, 35 TIMI 3 Infarct size by SPECT, The clinical end points were all-cause mortality, reinfarction Abciximab flow grade Death, Reinfarction, rate, and major bleeding events at 30 days follow-up. major Bleeding, and hemorrhagic Stroke Alteplase, 10 TIMI 3 ACE= Death,
Recommended publications
  • Urokinase, a Promising Candidate for Fibrinolytic Therapy for Intracerebral Hemorrhage
    LABORATORY INVESTIGATION J Neurosurg 126:548–557, 2017 Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage *Qiang Tan, MD,1 Qianwei Chen, MD1 Yin Niu, MD,1 Zhou Feng, MD,1 Lin Li, MD,1 Yihao Tao, MD,1 Jun Tang, MD,1 Liming Yang, MD,1 Jing Guo, MD,2 Hua Feng, MD, PhD,1 Gang Zhu, MD, PhD,1 and Zhi Chen, MD, PhD1 1Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing; and 2Department of Neurosurgery, 211st Hospital of PLA, Harbin, People’s Republic of China OBJECTIVE Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fi- brinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study. METHODS Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor–κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH. RESULTS In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH.
    [Show full text]
  • Fibrinolysis and Anticoagulant Potential of a Metallo Protease Produced by Bacillus Subtilis K42
    Fibrinolysis and anticoagulant potential of a metallo protease produced by Bacillus subtilis K42 WESAM AHASSANEIN, ESSAM KOTB*, NADIA MAWNY and YEHIA AEL-ZAWAHRY Department of Microbiology, Faculty of Science, Zagazig University, Zagazig, Egypt 44519 *Corresponding author (Email, [email protected]) In this study, a potent fibrinolytic enzyme-producing bacterium was isolated from soybean flour and identified as Bacillus subtilis K42 and assayed in vitro for its thrombolytic potential. The molecular weight of the purified enzyme was 20.5 kDa and purification increased its specific activity 390-fold with a recovery of 14%. Maximal activity was attained at a temperature of 40°C (stable up to 65°C) and pH of 9.4 (range: 6.5–10.5). The enzyme retained up to 80% of its original activity after pre-incubation for a month at 4°C with organic solvents such as diethyl ether (DE), toluene (TO), acetonitrile (AN), butanol (BU), ethyl acetate (EA), ethanol (ET), acetone (AC), methanol (ME), isopropanol (IP), diisopropyl fluorophosphate (DFP), tosyl-lysyl-chloromethylketose (TLCK), tosyl-phenylalanyl chloromethylketose (TPCK), phenylmethylsulfonylfluoride (PMSF) and soybean trypsin inhibitor (SBTI). Aprotinin had little effect on this activity. The presence of ethylene diaminetetraacetic acid (EDTA), a metal-chelating agent and two metallo protease inhibitors, 2,2′-bipyridine and o-phenanthroline, repressed the enzymatic activity significantly. This, however, could be restored by adding Co2+ to the medium. The clotting time of human blood serum in the presence of this enzyme reached a relative PTT of 241.7% with a 3.4-fold increase, suggesting that this enzyme could be an effective antithrombotic agent.
    [Show full text]
  • Eptifibatide Is Noninferior to Abciximab: Implications for Clinical Practice
    RESEARCH HIGHLIGHTS ANTIPLATELET THERAPY Eptifibatide is noninferior to abciximab: implications for clinical practice he glycoprotein IIb/IIIa (GPIIb/ randomized, open, parallel-group January 2004 and December 2007, IIIa) inhibitors eptifibatide and comparison of eptifibatide and abciximab and eptifibatide was used in 2,355 Tabciximab have comparable efficacy in 427 patients presenting within 12 h such procedures over this time frame. and safety in patients with ST-segment of STEMI onset and who underwent During the 1-year follow-up period, elevation myocardial infarction (STEMI) primary PCI. Enrolled patients were from no significant difference was reported undergoing primary percutaneous 22 centers in France and Germany. The for the incidence of death (8.0% and coronary intervention (PCI). These two study drugs were administered in 7.6%), myocardial infarction (9.0% and findings, from a randomized trial and a combination with background therapy 8.4%), or bleeding (2.7% and 3.2%) registry study, are reported in two papers comprising clopidogrel, aspirin, and between abciximab and eptifibatide, published in the Journal of the American heparin or enoxaparin. This study used respectively. Multivariable analysis College of Cardiology (JACC). the surrogate primary end point of showed that eptifibatide was noninferior Platelet aggregation and thrombus complete electrocardiographic ST-segment to abciximab for the prevention of death formation can be inhibited by blocking resolution (STR) 60 min after completion or myocardial infarction (odds ratio 0.94, the GPIIb/IIIa receptor on the platelet of PCI. 95% CI 0.82–1.09). membrane, thereby preventing the binding In the intention-to-treat analysis, These findings “fuel an already much of fibrinogen.
    [Show full text]
  • The Role of Low-Molecular-Weight Heparin in the Management of Acute Coronary Syndromes Marc Cohen, MD, FACC Newark, New Jersey
    CORE Metadata, citation and similar papers at core.ac.uk Provided by ElsevierJournal - ofPublisher the American Connector College of Cardiology Vol. 41, No. 4 Suppl S © 2003 by the American College of Cardiology Foundation ISSN 0735-1097/03/$30.00 Published by Elsevier Science Inc. doi:10.1016/S0735-1097(02)02901-7 The Role of Low-Molecular-Weight Heparin in the Management of Acute Coronary Syndromes Marc Cohen, MD, FACC Newark, New Jersey A substantial number of clinical studies have consistently demonstrated that low-molecular- weight heparin (LMWH) compounds are effective and safe alternative anticoagulants to unfractionated heparins (UFHs). They have been found to improve clinical outcomes in acute coronary syndromes and to provide a more predictable therapeutic response, longer and more stable anticoagulation, and a lower incidence of UFH-induced thrombocytopenia. Of the several LMWH agents that have been studied in large clinical trials, including enoxaparin, dalteparin, and nadroparin, not all have shown better efficacy than UFH. Enoxaparin is the only LMWH compound to have demonstrated sustained clinical and economic benefits in comparison with UFH in the management of unstable angina/ non–ST-segment elevation myocardial infarction (NSTEMI). Also, LMWH appears to be a reliable and effective antithrombotic treatment as adjunctive therapy in patients undergoing percutaneous coronary intervention. Clinical trials with enoxaparin indicate that LMWH is effective and safe in this indication, with or without the addition of a glycoprotein IIb/IIIa inhibitor. The efficacy demonstrated by enoxaparin in improving clinical outcomes in unstable angina/NSTEMI patients has led to investigations of its role in the management of ST-segment elevation myocardial infarction.
    [Show full text]
  • The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’S Perspective
    International Journal of Molecular Sciences Review The Central Role of Fibrinolytic Response in COVID-19—A Hematologist’s Perspective Hau C. Kwaan 1,* and Paul F. Lindholm 2 1 Division of Hematology/Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA 2 Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; [email protected] * Correspondence: [email protected] Abstract: The novel coronavirus disease (COVID-19) has many characteristics common to those in two other coronavirus acute respiratory diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). They are all highly contagious and have severe pulmonary complications. Clinically, patients with COVID-19 run a rapidly progressive course of an acute respiratory tract infection with fever, sore throat, cough, headache and fatigue, complicated by severe pneumonia often leading to acute respiratory distress syndrome (ARDS). The infection also involves other organs throughout the body. In all three viral illnesses, the fibrinolytic system plays an active role in each phase of the pathogenesis. During transmission, the renin-aldosterone- angiotensin-system (RAAS) is involved with the spike protein of SARS-CoV-2, attaching to its natural receptor angiotensin-converting enzyme 2 (ACE 2) in host cells. Both tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) are closely linked to the RAAS. In lesions in the lung, kidney and other organs, the two plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator (tPA), along with their inhibitor, plasminogen activator 1 (PAI-1), are involved. The altered fibrinolytic balance enables the development of a hypercoagulable Citation: Kwaan, H.C.; Lindholm, state.
    [Show full text]
  • Deliverable 5.A Interim Report on the Study Results APPENDIX 2
    Deliverable 5.a Interim report on the study results APPENDIX 2: Algorithms used to identify study variables for service contract EMA/2011/38/CN ‐ PIOGLITAZONE November 28th 2012 D5.a Interim report on the study results (Appendix 2) for Service Contract EMA/2011/38/CN PIOGLITAZONE Author(s): Vera Ehrenstein (AUH‐AS) APPENDIX 2. ALGORITHMS USED TO IDENTIFY STUDY VARIABLES Algorithms for AU Database DISEASE/CONDITION ICD-8 CODE (1977-1993) ICD-10 CODE (1994-) Diabetes type 2 250.00; 250.06; 250.07; 250.09 E11.0; E11.1; E11.9 Cancer of bladder 188 C67 Haematuria N/A R31 Haematuria, unspecified B18, K70.0–K70.3, K70.9, K71, K73, Mild hepatic impairment 571, 573.01, 573.04 K74, K76.0 Moderate to severe hepatic 070.00, 070.02, 070.04, 070.06, B15.0, B16.0, B16.2, B19.0, K70.4, impairment 070.08, 573.00, 456.00–456.09 K72, K76.6, I85 Acute myocardial infarction 410 I21-I23 Acute coronary syndrome 410, 413 I20-I24 Ischemic heart disease 410-414 I20-I25 427.09, 427.10, 427.11, 427.19, Congestive heart failure I50, I11.0, I13.0,I13.2 428.99, 782.49; Acute renal failure N/A N17 Diabetic coma N/A E10.0, E11.0, E12.0,E13.0, E14.0 Diabetic acidosis N/A E10.1, E11.1, E12.1,E13.1, E14.1 F10.1-F10.9, G31.2, G62.1, G72.1, Alcoholism 291, 303, 577.10, 571.09, 571.10 I42.6, K29.2, K86.0, Z72.1 Obesity 277.99 E65-E66 D5.a Interim report on the study results (Appendix 2) for Service Contract EMA/2011/38/CN PIOGLITAZONE Author(s): Vera Ehrenstein (AUH‐AS) Algorithms for defining acute events in Denmark, ICD-10 code Event ICD-10 code I21.x, I23.x http://apps.who.int/classifications/icd10/browse/2010/en#/I21
    [Show full text]
  • Reperfused STEMI Patients Lession from ISACS-TC
    What do to with late comer and/or non- reperfused STEMI patients Lession from ISACS-TC Raffaele Bugiardini Universita’ Alma Mater Studiorum Bologna Dubrovnik, 26-29 September 2013 International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-CT) Rationale and Design 1 • Mortality from cardiovascular disease has been decreasing continuously in the United States and many Western European countries, but it has increased or remained unchanged in many of the states of Eastern Europe. Analysis of this phenomenon has been hindered by insufficient information. • Much has been hypothesised about the ethnicity- and poverty-associated disparities in mortality when comparing Eastern with Western European countries. • Yet, identifying underlying causes for these worrisome geographic health patterns continues to challenge health care providers and researchers. International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-CT) Rationale and Design 2 Both a retrospective (over a one year period) and prospective (over a three year period) study which was designed in order to obtain data of patients with acute coronary syndromes in countries with economy in transition, and herewith control and optimize internationally guideline recommended therapies in these countries. There are a total of 132 Collaborating Centers in 17 transitional countries (Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Hungary, Kosovo, Moldova, Latvia, Lithuania, Poland, Russian Federation, Romania, Macedonia, Serbia, Slovakia, Slovenia,
    [Show full text]
  • ACTIVASE (Alteplase) for Injection, for Intravenous Use Initial U.S
    Application 103172 This document contains: Label for ACTIVASE [Supplement 5203, Action Date 02/13/2015] Also available: Label for CATHFLO ACTIVASE [Supplement 5071, Action Date 01/04/2005] HIGHLIGHTS OF PRESCRIBING INFORMATION Acute Ischemic Stroke These highlights do not include all the information needed to use • Current intracranial hemorrhage. (4.1) ACTIVASE safely and effectively. See full prescribing information for • Subarachnoid hemorrhage. (4.1) ACTIVASE. Acute Myocardial Infarction or Pulmonary Embolism • History of recent stroke. (4.2) ACTIVASE (alteplase) for injection, for intravenous use Initial U.S. Approval: 1987 -----------------------WARNINGS AND PRECAUTIONS-----------------------­ • Increases the risk of bleeding. Avoid intramuscular injections. Monitor for ---------------------------INDICATIONS AND USAGE--------------------------­ bleeding. If serious bleeding occurs, discontinue Activase. (5.1) Activase is a tissue plasminogen activator (tPA) indicated for the treatment of • Monitor patients during and for several hours after infusion for orolingual • Acute Ischemic Stroke (AIS). (1.1) angioedema. If angioedema develops, discontinue Activase. (5.2) • Acute Myocardial Infarction (AMI) to reduce mortality and incidence of • Cholesterol embolism has been reported rarely in patients treated with heart failure. (1.2) thrombolytic agents. (5.3) Limitation of Use in AMI: the risk of stroke may be greater than the benefit • Consider the risk of reembolization from the lysis of underlying deep in patients at low risk of death
    [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]
  • AHS Provincial High-Alert Medication List
    Provincial High-alert Medication List Classes/Categories of Medications Specific Medications adrenergic agonists: IV (e.g., epiNEPHrine, ePHEDrine, isoproterenol, magnesium sulfate injection PHENYLephrine, norepinephrine, doBUTamine, doPAMine, salbutamol) methotrexate: oral for non-oncologic adrenergic antagonists: IV (e.g., propranolol, metoPROLOL, labetalol, use esmolol) nitroprusside sodium for injection anesthetic agents: general, inhaled and IV (e.g., propofol, ketamine, sevoflurane, isoflurane, desflurane, etomidate) opium tincture antiarrhythmics: IV (e.g., lidocaine, amiodarone, procainamide, oxytocin: IV adenosine, bretylium, ibutilide) potassium chloride for injection: antithrombotic agents: concentrate anticoagulants (e.g., warfarin, acenocoumarol, tinzaparin, potassium phosphates injection enoxaparin, dalteparin, danaparoid, unfractionated heparin, sodium citrate) promethazine: IV factor Xa inhibitors (e.g., fondaparinux, rivaroxaban) vasopressin: IV or intraosseous direct thrombin inhibitors (e.g., apixaban, argatroban, bivalirudin, dabigatran) thrombolytics (e.g., alteplase, tenecteplase) glycoprotein IIb/IIIa inhibitors (e.g.,eptifibitide, tirofiban, abciximab) cardioplegic solutions chemotherapeutic agents: parenteral and oral dextrose: 20% or greater (hypertonic) dialysis solutions: peritoneal and hemodialysis The following medications are also epidural or intrathecal medications associated with higher risk and must inotropic medications: IV (e.g., digoxin, milrinone) comply with the segregated storage and labelling
    [Show full text]
  • Get with the Guidelines®-Stroke Is the American Heart Association's
    Get With The Guidelines®-Stroke is the American Heart Association’s collaborative performance improvement program, demonstrated to improve adherence to evidence-based care of patients hospitalized with stroke. The program provides hospitals with a Web-based Patient Management Tool™ (powered by QuintilesIMS), decision support, a robust registry, real-time benchmarking capabilities and other performance improvement methodologies toward the goal of enhancing patient outcomes and saving lives. This fact sheet provides an overview of the achievement, quality, descriptive, and reporting measures currently reported on via Get With The Guidelines-Stroke. Get With The Guidelines-Stroke is for patients with stroke and transient ischemic attack (TIA). The following is a list of the common stroke-related diagnoses included in Get With The Guidelines-Stroke: ICD-10: I60*; I61*; I63*; G45.0, G45.1, G45.8, G45.9 STROKE ACHIEVEMENT MEASURES ACUTE: • IV rt-PA arrive by 2 hour, treat by 3 hour: Percent of acute ischemic stroke patients who arrive at the hospital within 120 minutes (2 hours) of time last known well and for whom IV t-PA was initiated at this hospital within 180 minutes (3 hours) of time last known well. Corresponding measure available for inpatient stroke cases • Early antithrombotics: Percent of patients with ischemic stroke or TIA who receive antithrombotic therapy by the end of hospital day two. Corresponding measures available for observation status only & inpatient stroke cases • VTE prophylaxis: Percent of patients with ischemic stroke, hemorrhagic stroke, or stroke not otherwise specified who receive VTE prophylaxis the day of or the day after hospital admission. AT OR BY DISCHARGE: • Antithrombotics: Percent of patients with an ischemic stroke or TIA prescribed antithrombotic therapy at discharge.
    [Show full text]
  • Reperfusion Therapy in Acute Ischemic Stroke
    Bhaskar et al. BMC Neurology (2018) 18:8 DOI 10.1186/s12883-017-1007-y REVIEW Open Access Reperfusion therapy in acute ischemic stroke: dawn of a new era? Sonu Bhaskar1,2,3,4,6,7* , Peter Stanwell7, Dennis Cordato2,4,5, John Attia7,8 and Christopher Levi1,2,3,4,5,6* Abstract Following the success of recent endovascular trials, endovascular therapy has emerged as an exciting addition to the arsenal of clinical management of patients with acute ischemic stroke (AIS). In this paper, we present an extensive overview of intravenous and endovascular reperfusion strategies, recent advances in AIS neurointervention, limitations of various treatment paradigms, and provide insights on imaging-guided reperfusion therapies. A roadmap for imaging guided reperfusion treatment workflow in AIS is also proposed. Both systemic thrombolysis and endovascular treatment have been incorporated into the standard of care in stroke therapy. Further research on advanced imaging- based approaches to select appropriate patients, may widen the time-window for patient selection and would contribute immensely to early thrombolytic strategies, better recanalization rates, and improved clinical outcomes. Keywords: Stroke, Reperfusion therapy, Prognosis, Endovascular treatment, Neurointervention Background and up to 6–8 h for endovascular MT. The restriction on An overwhelming number of studies and clinical trials con- IV-tPA treatment beyond 4.5 h disqualifies the majority of firmtheefficacyofthrombolytictherapy,inagiventhera- stroke patients admitted beyond this time-window (around peutic window, in improving the clinical outcome and 85%), thereby drastically limiting the eligible population [7– recovery of acute ischemic stroke (AIS) patients [1–5]. The 10]. primary therapeutic goal for patients with AIS is the timely In this article, we review the literature on the various restoration of blood flow to salvageable ischemic brain reperfusion strategies available for AIS patients, and pro- tissue that is not already infarcted [6].
    [Show full text]