Accepted Article
Received Date : 27-Jan-2015 Revised Date : 16-Mar-2015 Accepted Date : 18-Mar-2015 Article type
: Review
Novel anticoagulants and antiplatelet agents; a guide for the urologist
Ellis G1, Camm AJ 2, Datta SN 3
Author Affiliations 1. Department of Urology, Whittington Hospital, London, UK 2. Department of Clinical Cardiology, St George’s Healthcare NHS Trust, London, UK 3. Department of Urology, Colchester University Hospital Foundation Trust, Colchester, UK
Corresponding Author Soumendra Datta [email protected]
Other Authors Ellis G – [email protected] Camm AJ – [email protected]
Conflicts of Interest None disclosed.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bju.13131 This article is protected by copyright. All rights reserved.
Accepted Article
Abstract: Novel Oral Anti-Coagulants (NOACs) are increasingly being used in clinical practice and are set to almost entirely replace the Vitamin K agonists, such as warfarin, in the near future. Similarly, new antiplatelet agents are now regularly used in place of older agents such as aspirin and clopidogrel. In an aging population, with an increasing burden of complex comorbidities, urologists will frequently encounter patients who will be using such agents. Some background knowledge, and an understanding, of these drugs and the issues that surround their usage is essential. This article will provide readers with an understanding of these new drugs, including their mechanisms of action, the up-to-date evidence justifying their recent introduction into clinical practice and the appropriate interval for stopping them prior to surgery. It will also consider the risks of peri-operative bleeding with regard to patients taking these drugs and the risks of venous thromboembolism in those in whom they are stopped. Strategies to manage anticoagulant-associated bleeding are discussed.
1 Introduction In an ageing population with an ever-increasing burden of comorbidities, more patients regularly take anticoagulant and antiplatelet agents. Aspirin, clopidogrel, heparin and warfarin have been in common use for several decades, and urologists are experienced in managing them peri-operatively. However, there are now numerous Novel Oral AntiCoagulants (NOACs) and new antiplatelet agents with more favourable characteristics that are increasingly being prescribed in clinical practice. The NOACs are expected to very nearly replace the vitamin K agonists, such as warfarin, in the near future. Similarly ticagrelor and prasugrel are preferred to clopidogrel by many physicians. Anticoagulants are used to prevent venous thromboembolism or propagation of existing thrombi. A second indication is the prevention of thromboembolism in patients with atrial fibrillation. Antiplatelets are used to prevent thrombus formation in a vessel, usually arterial, in which atherosclerosis is already evident. As urologists we frequently perform endoscopic and surgical procedures, many of which have a significant bleeding risk, and therefore an understanding of these agents, and how to manage them in the peri-operative period is essential. The dilemma clinicians face when considering stopping these medications peri-operatively is balancing the risk of bleeding during and after the procedure versus the risk of thrombosis incurred by stopping it1. Studies have shown that the highest cardiovascular risk to these patients may be in the period immediately after withdrawal2; this may be due to a rebound effect of platelet activation3,4. This means that having an understanding of the agent, its mechanism of action, any reversal agents and the time needed to return to the therapeutic status is mandatory for the surgeon. There is relatively little evidence and very few guidelines pertaining to the use of anticoagulants and antiplatelets in urology. A number of smallish studies have looked at use of Aspirin and Warfarin in TRUS biopsy, and have generally found that use of low dose Aspirin5,6,7 and perhaps even Warfarin8 is relatively safe. This article summarises the essential information on each of these novel agents licensed for use in the UK and provides the evidence to urologists for the most appropriate interval for stopping these drugs prior to surgery.
This article is protected by copyright. All rights reserved.
Accepted Article
Dabigatran
Apixaban
Edoxaban
Rivaroxaban
Procedural risk
Low
High
Low
High
Low
High
Low
High
CrCl ≥80 ml/min
≥24 h
≥48 h
≥24 h
≥48 h
No data
No data
≥24 h
≥48 h
CrCl 50–80 ml/min
≥36 h
≥72 h
≥24 h
≥48 h
No data
No data
≥24 h
≥48 h
CrCl 30–50 ml/min
≥48 h
≥96 h
≥24 h
≥48 h
No data
No data
≥24 h
≥48 h
CrCl 15–30 ml/min
Not indicated
Not indicated
≥36 h
≥48 h
No data
No data
≥36 h
≥48 h
CrCl
Received Date : 27-Jan-2015 Revised Date : 16-Mar-2015 Accepted Date : 18-Mar-2015 Article type
: Review
Novel anticoagulants and antiplatelet agents; a guide for the urologist
Ellis G1, Camm AJ 2, Datta SN 3
Author Affiliations 1. Department of Urology, Whittington Hospital, London, UK 2. Department of Clinical Cardiology, St George’s Healthcare NHS Trust, London, UK 3. Department of Urology, Colchester University Hospital Foundation Trust, Colchester, UK
Corresponding Author Soumendra Datta [email protected]
Other Authors Ellis G – [email protected] Camm AJ – [email protected]
Conflicts of Interest None disclosed.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bju.13131 This article is protected by copyright. All rights reserved.
Accepted Article
Abstract: Novel Oral Anti-Coagulants (NOACs) are increasingly being used in clinical practice and are set to almost entirely replace the Vitamin K agonists, such as warfarin, in the near future. Similarly, new antiplatelet agents are now regularly used in place of older agents such as aspirin and clopidogrel. In an aging population, with an increasing burden of complex comorbidities, urologists will frequently encounter patients who will be using such agents. Some background knowledge, and an understanding, of these drugs and the issues that surround their usage is essential. This article will provide readers with an understanding of these new drugs, including their mechanisms of action, the up-to-date evidence justifying their recent introduction into clinical practice and the appropriate interval for stopping them prior to surgery. It will also consider the risks of peri-operative bleeding with regard to patients taking these drugs and the risks of venous thromboembolism in those in whom they are stopped. Strategies to manage anticoagulant-associated bleeding are discussed.
1 Introduction In an ageing population with an ever-increasing burden of comorbidities, more patients regularly take anticoagulant and antiplatelet agents. Aspirin, clopidogrel, heparin and warfarin have been in common use for several decades, and urologists are experienced in managing them peri-operatively. However, there are now numerous Novel Oral AntiCoagulants (NOACs) and new antiplatelet agents with more favourable characteristics that are increasingly being prescribed in clinical practice. The NOACs are expected to very nearly replace the vitamin K agonists, such as warfarin, in the near future. Similarly ticagrelor and prasugrel are preferred to clopidogrel by many physicians. Anticoagulants are used to prevent venous thromboembolism or propagation of existing thrombi. A second indication is the prevention of thromboembolism in patients with atrial fibrillation. Antiplatelets are used to prevent thrombus formation in a vessel, usually arterial, in which atherosclerosis is already evident. As urologists we frequently perform endoscopic and surgical procedures, many of which have a significant bleeding risk, and therefore an understanding of these agents, and how to manage them in the peri-operative period is essential. The dilemma clinicians face when considering stopping these medications peri-operatively is balancing the risk of bleeding during and after the procedure versus the risk of thrombosis incurred by stopping it1. Studies have shown that the highest cardiovascular risk to these patients may be in the period immediately after withdrawal2; this may be due to a rebound effect of platelet activation3,4. This means that having an understanding of the agent, its mechanism of action, any reversal agents and the time needed to return to the therapeutic status is mandatory for the surgeon. There is relatively little evidence and very few guidelines pertaining to the use of anticoagulants and antiplatelets in urology. A number of smallish studies have looked at use of Aspirin and Warfarin in TRUS biopsy, and have generally found that use of low dose Aspirin5,6,7 and perhaps even Warfarin8 is relatively safe. This article summarises the essential information on each of these novel agents licensed for use in the UK and provides the evidence to urologists for the most appropriate interval for stopping these drugs prior to surgery.
This article is protected by copyright. All rights reserved.
Accepted Article
Dabigatran
Apixaban
Edoxaban
Rivaroxaban
Procedural risk
Low
High
Low
High
Low
High
Low
High
CrCl ≥80 ml/min
≥24 h
≥48 h
≥24 h
≥48 h
No data
No data
≥24 h
≥48 h
CrCl 50–80 ml/min
≥36 h
≥72 h
≥24 h
≥48 h
No data
No data
≥24 h
≥48 h
CrCl 30–50 ml/min
≥48 h
≥96 h
≥24 h
≥48 h
No data
No data
≥24 h
≥48 h
CrCl 15–30 ml/min
Not indicated
Not indicated
≥36 h
≥48 h
No data
No data
≥36 h
≥48 h
CrCl
