1 Hertfordshire guidelines for oral anticoagulation of patients with non-valvular AF *GUIDELINES FOR ORAL ANTICOAGULATION OF PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION (AF) TO PREVENT STROKE Contents Page Number Algorithm for the use of warfarin and non-vitamin K oral anticoagulants (NOACs) rivaroxaban, dabigatran and apixaban 2 1. Scoring Systems for assessing risk of and risk of bleeds CHA 2 DS 2 VASc scoring system to assess risk of 1.2 HAS-BLED scoring system to assess risk of major bleeds 2. Discussing risks and benefits of anticoagulation with patient/ carer 4 3. Choice of oral anticoagulation Patients for whom warfarin is the only option 3.2 Factors to consider when choosing an appropriate anticoagulant 4. Assessing anticoagulation control with warfarin 5 5. Baseline assessments and communication Baseline assessment to take prior to starting oral anticoagulants 5.2 Information to communicate across interfaces Appendices Appendix A Patient Information Leaflet - PIL 1: 6 AF & treatment options to reduce risk Risk of AF-related ischaemic benefits of anticoagulants Risk of effects of anticoagulation Appendix B Patient Information Leaflet - PIL 2: 9 Q&A document for patients on the differences in the treatment options between no treatment, warfarin and NOACs Appendix C AF anticoagulation clinical decision aid 11 - East of England Priorities Advisory Committee document These *guidelines have been updated by Pharmacy and Medicines Optimisation Team, E&NHCCG & HVCCG, based on: - NICE Clinical guidelines 180 June Hertfordshire Guidelines on use of novel oral anticoagulants, 25 April 2013 AF anticoagulant clinical decision Aid, EoE PAC, March 2015 *These guidelines are specific to the use of oral anticoagulants in the prevention of for people with non-valvular AF. The guidelines are not intended to cover any other aspects of the management of AF. Please refer to the NICE Clinical Guidelines 180 for further details on the management of AF.
2 Hertfordshire guidelines for oral anticoagulation of patients with non-valvular AF Algorithm for the use of Oral Anticoagulants (Warfarin & NOACs) for prevention in non valvular AF *People on warfarin INR Control Optimal INR control is defined as TTR>65%. Factors to consider in improving TTR: Patient education Adherence to prescribed therapy Inconvenient or inappropriate monitoring arrangements confirm suitability of arrangements for each patient. Consider domiciliary monitoring arrangements for patients with reduced mobility Cognitive function Illness Interacting drug therapy Lifestyle factors, including diet and alcohol consumption. For all patients deemed to have failed on warfarin therapy, establish relevant anticoagulant treatment history. Confirm evidence to support proposed reason for treatment failure e.g. Failed monitoring arrangements did the patient attend an anticoagulant monitoring service? Labile INR did the patient achieve a therapeutic INR? Bleeding complications was the bleed major/ minor? Confirm INR at time of bleed. Drug interactions any change to concurrent therapy should be considered. Serious ADR was this documented in patient records? Severe alopecia was the patient offered alternative VKA agents? **Patient Information Leaflets in this guideline are based on the NICE Patient Decision Aid for AF: /PatientDecisiionAid/pdf/English Non-valvular atrial fibrillation 1.1 Assess risk use CHA 2 DS 2 - VASc scoring system (see page 3) CHA 2 DS 2 -VASc =0 - Do not anticoagulate CHA 2 DS 2 -VASc =1 - Consider anticoagulant for men, but not for women who score one point for gender alone. CHA 2 DS 2 -VASc >2 - Offer anticoagulant 1.2 Assess bleeding risk use HAS-BLED scoring system (see page 3 and enter score on PIL 1 and 2) Address modifiable risk factors and monitor for change over time 2. Discuss AF, risk and benefits/risks of oral anticoagulant (OAC) treatment options with patient/ carer. The following leaflets** (PILs) are available to give to patients after discussion: PIL 1 Information about AF, and bleeding risk and treatment options Do not offer aspirin monotherapy solely for prevention in people with AF (associated harms outweigh limited benefit) Do not withhold anticoagulation solely because the person is at risk of having a fall Anticoagulation Patient is suitable for treatment and decides to take an oral anticoagulant PIL 2 Leaflet outlining differences between major groups of oral anticoagulants 3. Decide on Choice of OAC Tailor choice of OAC to the individual s clinical characteristics, values and personal preferences (see appendix 3, AF anticoagulation clinical decision aid) 4. Assess anticoagulation control with *warfarin see Page 5 and table opposite No anticoagulation CHA 2 DS 2 VASc =0 Anticoagulant declined/not tolerated/contra-indicated Consider left atrial appendage occlusion in line with NICE guidance (IPG349): This procedure should only be carried out by clinicians with specific training and appropriate experience and in units with on-site cardiac surgery Patient suitability to be assessed by multidisciplinary team. Discuss benefits and risks of procedure with person. The clinician may require more than one consultation with the patient to cover steps 1-3 to allow time for the patient to make an informed decision. 5. Communication If anticoagulation is initiated in secondary care, communication to GP to include the relevant information on baseline assessments, discussions with patient/carer and provision of patient information (see page 5 for further details) Reviewing people: 1. Who are not taking an anticoagulant because of bleeding risk or other factors: Review and bleeding risks annually, and ensure that all reviews and decisions are documented. 2. Who are taking an anticoagulant: Review the need for anticoagulation and the quality of anticoagulation at least annually, or more frequently if clinically relevant events occur, affecting anticoagulation or bleeding risk. NB: Regular clinical review of patients on NOACs is very important especially as such patients are likely to be monitored less frequently.
3 Hertfordshire guidelines for oral anticoagulation of patients with non-valvular AF 1. Scoring systems to assess risk of and risk of bleed 1.1 CHA 2 DS 2 -VASc scoring system for risk of + Scoring Calculator: 1.2 HASBLED scoring system for risk of bleed + Scoring Calculator: + Please note that online scoring calculators have not yet been updated to reflect ESC 2014 guidance upon which NICE CG180 is based. There may be slight variation in management advice. CHA 2 DS 2 -VASc scoring system for AF risk Eur Heart J (2013) doi: /eurheartj/eht291 Risk factor Score Present? Congestive heart failure or LVD 1 Hypertension history (controlled or uncontrolled) 1 Age 75 years or greater 2 Age years 1 Diabetes mellitus 1 Stroke, TIA or thromboembolism 2 Vascular disease (prior MI, PAD, aortic plaque) 1 Sex category female 1 TOTAL SCORE Interpretation of risk using the CHA 2 DS 2 -VASc score Friberg L et. al. Eur Heart J 2012; 33: CHA 2 DS 2 -VASc score Events per 100 patients/year Stroke/TIA/ peripheral emboli Ischaemic Events per 1000 patients/ year Ischaemic Stroke HAS-BLED scoring system for bleeding risk Eur Heart J (2013) doi: /eurheartj/eht291 Risk factor Score Present? Hypertension (uncontrolled eg systolic > 160mmHg, unresponsive to antihypertensives) Abnormal liver function (cirrhosis; bilirubin >2xnormal in association with AST/ALT/ALP >3x normal) Abnormal renal function (dialysis, transplant, Cr>2.3mg/dl or > 200 umol/l) 1 Stroke (prior history) 1 Bleeding (anaemia or predisposition to bleeding) 1 Labile INR (refers to unstable INRs/ high INRs or poor time in therapeutic range (e.g. TTR<60%). Elderly (Age 65yrs, frail) 1 Drugs (usage predisposing to bleeding eg anti-platelets, NSAIDs) 1 Alcohol (consumption of 8 or more alcoholic drinks per week) 1 Offer modification and monitoring of the following risk factors for bleeding: TOTAL SCORE Uncontrolled hypertension Poor control of INR ( labile INRs ) Concurrent medication e.g. aspirin, NSAID Harmful alcohol consumption Do not withhold anticoagulation soley because the person is at risk of having a fall. Interpretation of bleeding risk using the HAS-BLED score Friberg et al, Eur Heart J 2012; 33: HAS-BLED score Major bleeding events per 100 patients/ year in anticoagulant users 0 Major bleeding events per 1000 patients/year
4 Hertfordshire guidelines for oral anticoagulation of patients with non-valvular AF 2. Discussing risks and benefits of anticoagulation (NICE CG 180) Explain to person that: for most people the benefit of anticoagulation outweighs the bleeding risk for people with an increased risk of bleeding, the benefit of anticoagulation may not always outweigh the bleeding risk, and careful monitoring of bleeding risk is important. Use the following Patient Information Leaflets (PILs) to explain to patient/carer the treatments options and the risks and benefits of each option so that the decision for treatment is shared with the patient/carer. See leaflets available on the algorithm and at the end of this guideline: - The leaflets are adapted from the patient decision aid (PDA) tool on NICE website and are intended to support clinicians to make the patient /carer understand their personal risk of and bleeding and the impact of anticoagulation i.e. what matters most to the patient/carer to come to an informed decision taking into account their personal preferences. It is recommended that this is undertaken over 2 or more consultations with the patient/carer to absorb the information. Clinicians are encouraged to use these leaflets to ensure that patients/ carers own the decision. NICE has also developed a user guide for the PDA. It provides the background to and the scope of the PDA and also states the sources of data, methods and limitations. This is available on 3. Choice of oral anticoagulation NICE CG 180 states: Anticoagulation may be with vitamin K antagonist (warfarin) or non-vitamin K oral anticoagulants (apixaban, dabigatran etexilate, rivaroxaban). Patients with non-valvular atrial fibrillation not on OAC (NEW Patient) 3.1 Warfarin is the only option in: Patients with CrCl < 15ml/min or other absolute contraindications to NOAC. Note that: o Dabigatran is contra-indicated at CrCl 30ml/min o Rivaroxaban is contra-indicated at CrCl 15ml/min, AND rivaroxaban dose should be reduced to 15mg once daily at CrCl= 15-49ml/min o Apixaban is contra-indicated at CrCl 15ml/min AND apixaban dose should be reduced in patients with at least two of the following: age 80 years, body weight 60 kg, or serum creatinine 1.5 mg/dl (133 micromol/l). Patients with creatinine clearance ml/min should receive a lower dose of apixaban, 2.5 mg twice daily Patients with metallic heart valves, prior valve surgery or mitral stenosis the treatment of patients with valvular atrial fibrillation is outside the scope of this guideline. 3.2 For all other patients, tailor the choice of anticoagulant to individual patient s clinical characteristics, values and preferences. For patients see Appendix 2: PIL 2 Leaflet outlining differences between major groups of oral anticoagulants For healthcare professionals, the key points outlined in the table below: - Warfarin INR monitoring required. INR gives clinicians a guide to patient compliance. Oral antidote (vitamin K) to reverse effects of warfarin on INR. Warfarin is known to interact with certain foods containing high amounts of vitamin K. This is only a problem if patients make major changes in diet. NOACs No requirement for anticoagulation monitoring. Difficult to monitor compliance. No published systematic clinical studies on the reversal of the anticoagulant effects of the drugs. NOACs currently have no known food interactions. Please also see Appendix C: AF anticoagulation clinical decision aid for further detailed information on factors to consider when choosing between anticoagulation options. see
5 Hertfordshire guidelines for oral anticoagulation of patients with non-valvular AF 4. Assessing anticoagulation control with warfarin 4.1 Calculate the person s time in therapeutic range (TTR) at each visit. When calculating TTR: Use a validated measurement method Exclude measurements taken during the first 6 weeks of treatment Calculate TTR over a maintenance period of at least 6 months 4.2 Reassess anticoagulation for a person with poor anticoagulation control shown by any of the following: 2 INR values higher than 5 OR 1 INR value higher than 8 within the past 6 months 2 INR values less than 1.5 within the past 6 months TTR less than 65% 4.3 When reassessing, take into account and if possible address the factor that may contribute to poor control: - Patient education Cognitive function Adherence to prescribed therapy Illness Interacting drugs Lifetstyle factors including diet and alcohol Inconvenient/inapproapriate monitoring arrangements confirm suitability Consider domicillary monitoring arrangements for patient with reduced mobility 4.4 If poor INR control cannot be improved, evaluate the risks and benefits of alternative prevention strategies and discuss this with the patient. 5. Baseline assessments and communication 5.1 Baseline assessment to undertake Prior to starting an anticoagulant, the following baseline assessment is important: - Assessment Reason for undertaking CHA 2 DS 2 VASc HAS-BLED score Renal function as creatinine clearance Haemoglobin Platelets To help communicate to patient their individual risk. To estimate individual bleeding risk and address modifiable risk factors and to communicate individual risk to patient. For safety reasons. Helps with choice, dosing and estimate of frequency of future monitoring. For safety reasons. To get baseline value for future monitoring. To get a baseline value when monitoring bleeding risk in patients. 5.2 Communication across secondary/ primary care interface Information to be transferred to GPs. Letters to GPs from secondary care, when anticoagulation has been initated in secondary care, to include all of the following information: Baseline assessment results: CHA 2 DS 2 VASc score; HAS-BLED score; renal function as CrCl; haemoglobin; platelets Discussion with patient/carer: Likelihood of in the individual patient in next year Likelihood of benefit with OAC (NB: It is important that patients/ carer understand that there is never 100% certainty that treated patients will not get a ). Likelihood of in next year Implications of OAC on Choice of OAC. Please see Appendix D: Clinical Screening Checklist and FAQs for NOACs (factors to consider when choosing between NOACs) Information to be given to patient: Anticoagulant alert card Information for monitoring bleeds Patient leaflet on oral anticoagulants Guidelines Updated: September 2014
6 Appendix A: PIL 1 Risk of AF & benefits of OAC, Risk of major bleeds & effects of OAC PATIENT INFORMATION LEAFLET 1 (PIL 1): Atrial fibrillation & treatment options to reduce risk What is atrial fibrillation? Atrial fibrillation (AF) is a condition that causes the heart to beat irregularly and too fast. Blood does not flow properly through the heart and the rest of the body so people with AF may be at increased risk of blood clots which can block blood vessels causing a to happen. The most common type of is called an ischaemic which happens when a blood clot blocks a blood vessel in the brain blocking the blood supply and damaging or destroying brain cells because they do not receive enough oxygen (which is carried by the blood). A can affect many different body functions, depending on the part of the brain that is involved. Symptoms of include: Numbness Weakness or lack of movement on one side of the body Slurred speech Difficulty finding words or understanding speech Confusion Problems with vision Sometimes a is so severe it can kill the person straight away. Blood clots can also block blood vessels in different parts of the body and depending on where this happens, different organs might be seriously damaged because they do not receive enough oxygen. Treatment options to reduce your risk of having a A medicine called an anticoagulant helps reduce the risk of an ischaemic caused by AF. Anticoagulants make the blood take longer to clot (sometimes called thinning the blood ). This reduces the risk of a blood vessel in the brain (and elsewhere in the body) being blocked by a clot. Treatment with anticoagulation is usually long term. You can choose whether to take an anticoagulant or not. If you decide to take one, you will then need to decide which one you want to use. There are two groups of anticoagulants warfarin (which has been used for many years and belongs to a group called vitamin K antagonists) or newer drugs - apixaban, dabigatran and rivaroxaban. These work in a different way to warfarin, so they are often called novel or new or non-vitamin K oral anticoagulants, or NOACs, for short. Risk of major internal bleeding Making blood take longer to clot reduces the risks of having an ischaemic. But blood clots are the body s way of stopping the bleeding if you have an injury. So, although anticoagulants can reduce your risk of ischaemic, they can also increase the risk of bleeding such as nose bleed and bruising more easily, and also major (that is serious, excessive) internal bleeding. Major bleeding is most likely to happen after an injury or during an operation and is most dangerous when it happens in the brain and causes another type of called a haemorrhagic. Major bleeding outside of the brain usually needs to be treated with a blood transfusion. Sometimes can kill a person, especially if it happens inside the brain and is not treated straight away.
7 Appendix A: PIL 1 Risk of AF & benefits of OAC, Risk of major bleeds & effects of OAC All the different anticoagulants reduce your risk of having an ischaemic caused by your AF, but they also increase the risk that you will have, which might even include a haemorrhagic. Each treatment also has other advantages and disadvantages that different people feel differently about. The leaflets will give you the information about these advantages and disadvantages to help you and your health care professional make the best choice for you. Not all of the treatment options may be suitable or possible for you depending on your personal circumstances and other medical conditions you may have, for example if you have certain types of kidney problems. Your healthcare professional will tell you if this applies to you. There is a lot of information in these leaflets that you will need to think about before you decide whether to take an anticoagulant or not, and if so, which one you want to use. If you have just been diagnosed with AF you will need to make a decision soon (preferably within a few days), but most people do not have to make the decision immediately. Treatment with an anticoagulant is usually long term, so it is important that you are happy with your choice. Once you have made a choice, you can change your mind later if you wish or if your situation changes. Your risk of having a or having can also change over time, so your healthcare professional will review your risk at least once a year. If you decide not to take an anticoagulant now, you should think about this decision again then. What does NICE recommend? NICE recommends that most people with AF should think about taking an anticoagulant, taking into account how likely it is that they might have an ischaemic or. NICE recommends that your healthcare professional should use risk scores to estimate your risk of (called the CHA 2 DS 2 VASc) and the risk of bleeding (called the HAS-BLED). Please ask your healthcare professional to record your risk scores below: - My CHA 2 DS 2 VASc score is My HAS-BLED score is The risk score is based on factors such as your age and if you have any other medical conditions. The higher the score, the more likely it is that you will have either a or. However, it is important to remember that: - No one can tell what will happen to an individual person Even if your scores are low or zero, you might still have an ischaemic or If your scores are high, it does not mean that you will definitely have a or Taking an anticoagulant will save some people from having an ischaemic caused by AF, but some people will still have an ischaemic even though they take the anticoagulant. Although taking an anticoagulant increases the risk of, this will not happen to many people taking this medicine; some people will have even if they don t take an anticoagulant.
8 Appendix A: PIL 1 Risk of AF & benefits of OAC, Risk of major bleeds & effects of OAC The following tables can be used to explain the impact that the benefits and risks have on you personally according to your stoke and bleeding risks scores. The table shows: - The risk of AF-related ischaemic over 1 year in a group of 1000 people with AF, depending on their CHA 2 DS 2 VASc score, and how taking anticoagulant treatment can have benefits and reduce the risk The risk of over 1 year in a group of 1000 people with AF, depending on their HAS-BLED score, and how taking an anticoagulant can increase the risk Your healthcare professional will tick the relevant box for your individual and bleeding risk scores. Only look at the section that applies to your CHA 2 DS 2 VASc and HAS-BLED score. You will see what your personal risk is (in a group of 1000 people treated for 1 year) if you take no treatment compared to the benefits of taking anticoagulants and how this treatment will then affect your bleeding risk (also for 1000 patients over 1 year). CHA 2 DS 2 VASc score Risk of AF-related ischaemic benefits of anticoagulants No treatment 6 people would have a 994 would not have a 25 people would have a 975 would not have a 37 people would have a 963 would not have a 55 people would have a 945 would not have a 84 people would have a 916 would not have a Anticoagulant 4 people will be saved from having a 994 will not have, but would not have done anyway 2 people will still have a 17 people will be saved from having a 975 will not have, but would not have done anyway 8 people will still have a 25 people will be saved from having a 963 will not have, but would not have done anyway 12 people will still have a 38 people will be saved from having a 945 will not have, but would not have done anyway 17 people will still have a 57 people will be saved from having a 916 will not have, but would not have done anyway 27 people will still have a HAS-BLED score Risk of effects of anticoagulants No treatment 3 people would have 997 would not have major bleeding 7 people would have 993 would not have major bleeding 9 people would have 991 would not have major bleeding 13 people would have 987 would not have major bleeding Anticoagulant An extra 4 people will have 993 will not have 3 people will have major bleeding, just as they would have done anyway An extra 12 people will have 981 will not have 7 people will have major bleeding, just as they would have done anyway An extra 15 people will have 976 will not have 9 people will have major bleeding, just as they would have done anyway An extra 21 people will have 966 will not have 13 people will have major bleeding, just as they would have done anyway 8
9 PATIENT INFORMATION LEAFLET 2 (PIL 2): Questions on the differences in the treatment options QUESTION 1. What is this option? 2. Will it reduce my risk of having a? 3. Will it increase my risk of having? 4. What are the other main side effects? 5. Will I need any regular blood tests? 6. What happens if I forget to take a dose Not taking anything You will not take anything TREATMENT OPTION Taking warfarin Taking a NOAC (apixaban, dabigatran or rivoraxaban) You will take tablet(s) once a day, usually in the evening. Apixaban take 1 tablet twice a day. The dose will be adjusted depending on blood test results Dabigatran take 1 capsule twice a day. (see question 5). You will have written instructions on how Rivaroxaban 1 tablet once a day. many tablets to take and an information booklet. You will stay on the same dose all the time. You will normally need to take warfarin and NOACs long term Please see the table in the Patient Information Leaflet 1 which shows your risk of having a depending on your CHA 2 DS 2 VASc score, over 1 year for no treatment and for when you take an anticoagulant. Please see the table in the Patient Information Leaflet 1 which shows your risk of having depending on your HAS- BLED score, over 1 year for no treatment and for when you take an anticoagulant. This question does not apply This question does not apply This question does not apply Warfain and NOACs can cause side effects but not everyone gets them. The most common side effect is bleeding, including bruising and nose bleeds. See manufaturer s patient information leaflet for warfarin for full list of side effects. YES. For the first few weeks or months, you will need frequent blood tests. After that, most people need to have these tests every 1-2 months. Some people will need blood tests more or less often than this. You should take warfarin at the same time, every day. Since NOACs are newer drugs, all side effects are not yet known. See company information leaflets for apixaban, dabigatran and rivaroxaban for full list of side effects. YES. You will need a blood test before you start treatment to check how well your liver and kidneys are working, and then usually once every year, but not more often than that unless you have certain medical conditions. It is important to take the NOAC regularly as prescribed. The protective effect of the NOAC on the risk of fades hours after you take a dose. If you think you have missed a dose or taken an extra dose by mistake, then follow the instructions in the information booklet given to you or contact the health professional who monitors your treatment for advice. 9
10 Appendix B: PIL 2 Q&A for patients on the differences in the treatment options TREATMENT OPTION QUESTION Not taking anything Taking warfarin Taking a NOAC (apixaban, dabigatran or rivoraxaban) 7. Will I have to change what I eat and drink? This question does not apply Ask your health professional s advice before making any major changes to what you eat, especially foods rich in vitamin K (such as green leafy vegetables) because this may affect how your body responds to warfarin. Avoid drinking cranberry juice. If you drink alcohol, follow the national guidelines on how much is safe to drink and never binge drink. Written information will be given to you. No, there is no need to change what you eat or drink. 8. Will the medicine interact with other medicines I take? 9. What happens if I need non-urgent surgery, including dental surgery? 10. What happens if the effects need to be reversed in an emergency (for example, after an injury or before emergency surgery)? This question does not apply This question does not apply This question does not apply Warfarin and NOACs can interact with several medicines, including medicines bought over the counter and herbal medicines. It is important to ask the advice of your health professional before starting or stopping any medicines. See the company information leaflets links in Question 4 to warfarin and each of the NOACs for a full list of medicines which may interact. It is important to tell anyone treating you, including your dentist, that you are taking an anticoagulant. You should tell them well before your appointment and show them the alert card that you will be given. You would usually stop taking warfarin about 5 days before planned surgery, and start taking it again straight away afterwards. For dental surgery, you would not usually need to stop taking warfarin beforehand, but your blood clotting would be tested to help decide. You would usually stop taking the NOAC 48 hours before the planned surgery or dental treatment, and start taking the NOAC straight away after the sugery. You should carry the alert card that you will be given to tell anyone who treats you that you are taking warfarin or a NOAC. If you have a serious injury or need urgent surgery, you ar more likey to have because you take warfarin or a NOAC. It may be necessary to try to reverse the effects of warfarin or a NOAC if this occurs. Vitamin K is used as an antidote to reverse the effect of warfarin. This is well established and effective, and it is easy for medical staff to check what effect the warfarin is having on your blood s ability to clot. However, it is not always possible to reverse the effects of warfarin on clotting quickly or easily. The best ways to reverse the effects of NOACs are not so well established and there is currently no antidote. It is more difficult to measure what effect the NOAC is having on your blood s ability to clot. It may not be possible to reverse the effects of the NOAC on clotting quickly or easily.
11 Appendix C: AF anticoagulation clinical decision aid Appendix C Factors to consider when choosing between anticoagulant options and FAQs Choice of anticoagulant for non-valvular* atrial fibrillation: Clinical decision aid Patients should already be screened for an absolute contraindication to oral anticoagulation. This is a guide to the suitability of the patient for a NOAC versus warfarin and an indication to a preferred drug. Each of the following 10 factors should be considered and each drug rated using the key below to give the clinician a pointer to a preferred drug. Clinically suitable options must then be discussed with the patient before a drug is selected, taking into account patient preferences. Always refer to the current SPC for up to date prescribing information. 1-4 Key Symbol Definition Example ++ Strongly favours drug W++strongly favours warfarin + Favours drug R+ favours rivaroxaban - Not preferred agent D- dabigatran not preferred agent () Contraindicated (C/I) (A) apixaban contraindicated Absolute contraindications to NOACs (consider warfarin instead) 5,6 *Significant mitral valve stenosis or prosthetic valve (NB other valve pathology are not a C/I) Clinically significant active bleeding or acute haemorrhagic in the previous 14 days Known hypersensitivity, Pregnancy (any stage) In ischaemic within 2 weeks post, in view of risk of haemorrhagic transformation, risks and benefits of early anticoagulation need to be considered by determining the size of infarct and disability Check SPC of individual drugs for other specific contraindications 11
12 1. Renal function Appendix C: AF anticoagulation clinical decision aid >50ml/min Any agent Few patients with CrCl <50 ml/min have been studied in clinical trials; all NOACs have dose adjustments for varying 30-49ml/min W++, R+, A+, D- degrees of renal impairment. Monitor renal function closely in situations where it may deteriorate (e.g. elderly, heart failure). Switch before thresholds for C/I are reached ml/min W++, R+, A+, (D) Warfarin Dabigatran Rivaroxaban Apixaban <15ml/min W++, (R, A, D) 2. Liver function LFTs > 2x ULN W, R+, A-,(D) Dabigatran is not recommended and apixaban should be used with caution in patients with elevated liver enzymes > 2 x ULN. Apixaban is not recommended in patients with severe hepatic impairment. No anticoagulant is safe in the presence of a coagulopathy (any cause). Warfarin Dabigatran Rivaroxaban Apixaban 3. Elderly and frail Patient >75 years W+, R+, A-, D- The elderly and frail have an increased bleeding risk. Dose adjustments are required for dabigatran and apixaban depending on age & weight (see SPC). Warfarin Dabigatran Rivaroxaban Apixaban Patient <75 years Any agent 4. Ability/compliance with dosing Good Any agent Compliance may be easier if o.d. (warfarin or rivaroxaban) vs. b.d. (dabigatran, apixaban) but a missed dose may have more consequence for rivaroxaban. NB. if patient has poor medication compliance this can best be identified and monitored with warfarin. Warfarin Dabigatran Rivaroxaban Apixaban Poor W+, R-, A-, D- 5. Ability/compliance with monitoring Good Any agent Warfarin requires regular INR monitoring. None of the NOACs require routine anticoagulation testing but do require renal function monitoring at least yearly. % Time in Therapeutic Range* 65% Continue warfarin <65% Favours any NOAC * INR 2-3, assess over 6/12 but ignore first 6/52 of initiation. NICE recommend considering a NOAC if TTR < 65% or the patient has had extreme INRs (e.g. two > 5, one > 8 or two < 1.5 in last 6/12). 7 NB. Provided reason for range deviation is not correctible; review cognition, adherence, illness, drugs and lifestyle. Poor Favours any NOAC Warfarin Dabigatran Rivaroxaban Apixaban 12
13 6. History of major GI disease + GI bleeding event in past year Appendix C: AF anticoagulation clinical decision aid Yes W+, A+, R-, D- Both SPCs for dabigatran and rivaroxaban indicate increase risk for GI bleeding compared to warfarin. In addition, dabigatran has an increased incidence of dyspepsia. No Any agent Warfarin Dabigatran Rivaroxaban Apixaban 7. Ongoing need for concomitant medications that interact with a NOAC** Yes Favours warfarin Warfarin has many drug interactions, but has the INR as a means of monitoring and making dose adjustments. The NOACs have fewer drug interactions but no means of monitoring and little data on how to or whether to make dose adjustments. Consult SPC for up to date list of drug interactions 1-4 No Any agent Warfarin Dabigatran Rivaroxaban Apixaban ** Depending on NOAC, to varying degrees: verapamil, diltiazem, quinidine, amiodarone, dronedarone, some antifungals, antivirals and antibiotics. NB. list not exhaustive or specific to one NOAC. 8. Ongoing need for concomitant single or dual antiplatelet therapy No Any agent Patients taking OAC + aspirin + clopidogrel or higher dose aspirin were generally excluded from NOAC clinical Single Favours warfarin trials. Antiplatelets combined with any anticoagulant will increase bleeding risk. NICE recommend avoiding triple Dual Only warfarin and consider therapy, i.e. just warfarin + one antiplatelet if patient has had an MI or stent in the last 12/12 (clopidogrel if dropping one antiplatelet stented, otherwise aspirin). 8 NICE also recommends avoiding NOACs post MI or post-pci. 8 ASAP Warfarin Dabigatran Rivaroxaban Apixaban 9. Ongoing variable intake of excess alcohol or medications that interact with warfarin Yes Favours NOAC e.g. antibiotics for exacerbations of COPD, courses of steroids or patient is prone to binge drinking. Warfarin has many drug interactions, but has the INR as a means of monitoring and making dose adjustments. If frequent courses of medication upset control and they are not known to interfere with a NOAC, the NOAC may provide more stable anticoagulation. No Any agent Warfarin Dabigatran Rivaroxaban Apixaban 10. Need for monitored dosing system (MDS) Yes A+, R+, (W, D) Only rivaroxaban and apixaban can be put in an MDS. 9 Warfarin and dabigatran must be kept separate. No Any agent Warfarin Dabigatran Rivaroxaban Apixaban 13
14 AF dosing information APIXABAN - factors affecting dose Standard dose (no dose modifying factors present) Two or more of the following factors present: Creatinine >133μmol/l, Age > 80 yrs, weight < 60 kg CrCl ml/min CrCl < 15 ml/min DABIGATRAN - factors affecting dose Standard dose (no dose modifying factors present) Age > 80yrs or taking verapamil CrCl 30-50ml/min, or age 75-80yrs, or risk factors for bleeding CrCl < 30ml/min RIVAROXABAN - factors affecting dose CrCl >50ml/min CrCl ml/min CrCl ml/min CrCl <15ml/min Appendix C: AF anticoagulation clinical decision aid Dose 5mg BD 2.5mg BD 2.5mg BD Avoid Dose 150mg BD 110mg BD Consider 110mg BD instead of 150mg BD Avoid Dose 20 mg OD 15 mg OD Caution Avoid Switching anticoagulants Warfarin to a NOAC - For dabigatran and apixaban, start the drug once INR is < 2. F or rivaroxaban, start when INR 3. One NOAC to another NOAC - Take usual dose(s) of first drug on day prior to switch and usual doses of the new drug from the following morning. NOAC to warfarin - For dabigatran, the duration of concurrent treatment is based on renal function: CrCl 50 ml/ min: Start warfarin 3 days prior to stopping dabigatr an. CrCl ml/min: Start warfarin 2 days prior to stopping dabigatran. CrCl ml/min: Start warfarin 1 day prior to stopping dabigatran. For rivaroxaban, warfarin should be given concurrently until INR 2.0, with INR-guided dosing of warfarin used from day 3 of the transition period. NB. Rivaroxaban raises INR levels so test INR just before next dose of rivaroxaban. For apixaban, continue apixaban for at least 2 days after starting warfarin. Check INR just prior to next dose of apixaban and continue apixaban until INR 2.0. Peri-operative management In general, NOACs should be stopped before invasive or surgical procedures and restarted promptly when haemostasis has been restored. Many minor operations that can be performed with concomitant warfarin may be safe to perform if a NOAC is taken (e.g. dental extraction). For dabigatran, stopping distance is based on renal function: CrCl 80 ml/ min: Stop dabigatr an 24 hours pre-procedure. CrCl ml/min: Stop dabigatran 1-2 days pre-procedure. CrCl ml/min: Stop dabigatran 2-3 days pre-procedure. NB. Also add 1-2 days to above if there is a high risk of bleeding or major surgery planned. For rivaroxaban, stop at least 24 hours pre-procedure. For apixaban, stop at least 48 hours prior to procedures with moderate-high risk of unacceptable/significant bleeding and 24 hours prior to low risk procedures. Management of bleeding Standard measures to control bleeding and maintain haemostasis should be used. Fresh frozen plasma (FFP) has no role and there is no licensed or well researched antidote. The short half-life of NOACS is in their favour. Activated prothrombin complex concentrate may have some effect. Monitoring requirements: 1. ALL patients on long term anticoagulants require a general review at least once a year: Check risks and benefits are unchanged Assess if dose change is required Check compliance Check patient understanding of risks etc. see patient information. 2. Patients on NOACs should have renal function checked: Annually if CrCl > 60ml/min 6 monthly if CrCl 30-60ml/min 3 monthly if CrCl < 30ml/ min, 75 years or expected decline in renal function: During acute illness (dose many need to be modified- see above) 3. Patients on warfarin require checks as per local INR protocol and a check for time in therapeutic range every 6/12 14
15 Appendix C: AF anticoagulation clinical decision aid References 1. Summary of Product Characteristics - Eliquis 2.5 mg film-coated tablets, Bristol-Myers Squibb-Pfizer. Updated 30/07/14, accessed 28/10/14. https://www.medicines.org.uk/emc/medicine/ Summary of Product Characteristics - Xarelto 15mg film-coated tablets, Bayer plc. Updated 15/08/14, accessed 28/10/14. https://www.medicines.org.uk/emc/medicine/ Summary of Product Characteristics - Pradaxa 110 mg hard capsules, Boehringer Ingelheim Limited. Updated 15/08/14, accessed 28/10/14. https://www.medicines.org.uk/emc/medicine/ Summary of Product Characteristics - Marevan 1mg Tablets, Amdipharm Mercury Company Limited. Updated 26/05/14, accessed 28/10/14. https://www.medicines.org.uk/emc/medicine/ Hankey GJ, Norrving B, Hacke W, Steiner T. Management of acute in patients taking novel oral anticoagulants. International Journal of Stroke 2014;9(5): doi: / ijs National clinical guideline for, Prepared by the Intercollegiate Stroke Working Party, Fourth edition 2012 https://www.rcplondon.ac.uk/sites/default/files/national-clinicalguidelines-for--fourth-edition.pdf 7. NICE Clinical guideline 180. Atrial fibrillation: the management of atrial fibrillation. Published June NICE Clinical guideline 172. MI secondary prevention: Secondary prevention in primary and secondary care for patients following a myocardial infarction. Published November recommendations#drug-therapy-2 9. UKMi Medicines compliance aid database, accessed 07/11/
Hertfordshire Implementation of NICE TAs 249, 256 and 275 Apixaban, dabigatran and rivaroxaban, novel oral anticoagulants (NOACs) for the prevention of stroke and systemic embolism in non-valvular atrial
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