The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature

Persistent Link:
http://hdl.handle.net/10150/610256
Title:
The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature
Author:
Tahir, Faryal; Riaz, Haris; Riaz, Talha; Badshah, Maaz; Riaz, Irbaz; Hamza, Ameer; Mohiuddin, Hafsa
Affiliation:
Dow Medical College, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, Pakistan; Department of Medicine, Indiana University, Indianapolis, Indiana, USA; Department of Medicine, University of Arizona, Arizona, USA; Quaid-e-Azam Medical College, Bahawalpur, Pakistan
Issue Date:
2013
Publisher:
BioMed Central
Citation:
Tahir et al. Thrombosis Journal 2013, 11:18 http://www.thrombosisjournal.com/content/11/1/18
Journal:
Thrombosis Journal
Rights:
© 2013 Tahir et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions.METHODS:We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients".RESULTS:Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary.CONCLUSION:Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.
EISSN:
1477-9560
DOI:
10.1186/1477-9560-11-18
Keywords:
Vitamin K antagonists; Oral anticoagulants; Apixaban; Rivaroxaban; Dabigatran; Orthopedic surgery; Knee replacement; Hip replacement; Acute coronary syndrome; Atrial fibrillation; Venous thromboembolism; Critically ill patients; Systematic review
Version:
Final published version
Additional Links:
http://www.thrombosisjournal.com/content/11/1/18

Full metadata record

DC FieldValue Language
dc.contributor.authorTahir, Faryalen
dc.contributor.authorRiaz, Harisen
dc.contributor.authorRiaz, Talhaen
dc.contributor.authorBadshah, Maazen
dc.contributor.authorRiaz, Irbazen
dc.contributor.authorHamza, Ameeren
dc.contributor.authorMohiuddin, Hafsaen
dc.date.accessioned2016-05-20T09:02:22Z-
dc.date.available2016-05-20T09:02:22Z-
dc.date.issued2013en
dc.identifier.citationTahir et al. Thrombosis Journal 2013, 11:18 http://www.thrombosisjournal.com/content/11/1/18en
dc.identifier.doi10.1186/1477-9560-11-18en
dc.identifier.urihttp://hdl.handle.net/10150/610256-
dc.description.abstractBACKGROUND:Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions.METHODS:We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients".RESULTS:Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary.CONCLUSION:Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.thrombosisjournal.com/content/11/1/18en
dc.rights© 2013 Tahir et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.subjectVitamin K antagonistsen
dc.subjectOral anticoagulantsen
dc.subjectApixabanen
dc.subjectRivaroxabanen
dc.subjectDabigatranen
dc.subjectOrthopedic surgeryen
dc.subjectKnee replacementen
dc.subjectHip replacementen
dc.subjectAcute coronary syndromeen
dc.subjectAtrial fibrillationen
dc.subjectVenous thromboembolismen
dc.subjectCritically ill patientsen
dc.subjectSystematic reviewen
dc.titleThe new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literatureen
dc.typeArticleen
dc.identifier.eissn1477-9560en
dc.contributor.departmentDow Medical College, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, Pakistanen
dc.contributor.departmentDepartment of Medicine, Indiana University, Indianapolis, Indiana, USAen
dc.contributor.departmentDepartment of Medicine, University of Arizona, Arizona, USAen
dc.contributor.departmentQuaid-e-Azam Medical College, Bahawalpur, Pakistanen
dc.identifier.journalThrombosis Journalen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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