RIVAROXABAN FOR ATRIAL FIBRILLATION Amber Initiation Guideline

RIVAROXABAN FOR ATRIAL FIBRILLATION Amber Initiation Guideline The purpose of this guideline is to provide prescribing and monitoring advice on rivaroxaban in the treatment of AF for the prevention of stroke and systemic embolism in people with nonvalvular atrial fibrillation with a CHA 2 DS 2 VAS c score of one or more. This is a new indication for rivaroxaban for which there are clear risks and benefits. As a general rule rivaroxaban is only considered for prescribing where neither warfarin nor dabigatran are suitable. Use of rivaroxaban for treatment of DVT is hospital only for use in Buckinghamshire. This guideline should be read in conjunction with the Summary of Product Characteristics (SPC) available on www.medicines.org.uk/emc and the BNF. 1. BACKGROUND FOR USE The decision about whether to start treatment with rivaroxaban should be made after an informed discussion between the clinician and the person about the risks and benefits of rivaroxaban compared with warfarin and dabigatran. For people who are taking warfarin, the potential risks and benefits of switching to a new oral anticoagulant (NOAC) should be considered in light of their level of INR control 1.1. Risks/disadvantages of NOACs compared to warfarin 1.1.1. Long term safety of warfarin is well established. Warfarin has been in clinical use for more than 60 years, in contrast the safety profile of dabigatran & rivaroxaban are still not fully understood and there is no long term safety data. Rivaroxaban is under intensive surveillance by the MHRA. 1.1.2. There is limited knowledge of use of NOACs in certain patient groups, e.g. extremes of body weight, renal or hepatic impairment, women of child bearing potential, breast feeding mothers, age over 80. 1.1.3. Rates of GI symptoms/bleeds are greater with NOACs than warfarin. Major GI bleeding rates for dabigatran compared to warfarin are 2 : 1.56% vs 1.07% per year; GI side effects 11.3% vs 5.8% per year; NNH 18. Figures are based upon 150 mg twice daily dose. Simliarly rivaroxaban causes more GI bleeds than warfarin 5 3.2% compared to 2.2% 1.1.5. Overall there is a dose-related associated bleeding risk with NOACs. The relative risk of major bleeding with NOACs is believed to increase with age. 1.1.6. There is currently no licensed product available to rapidly reverse major bleeding with dabigatran or rivaroxaban. Warfarin is easier to reverse. The degree of anticoagulation with warfarin is measured using INR results. Dabigatran and rivaroxaban cannot be monitored using INR. However, death from bleeding does not appear to be increased in patients taking NOAC drugs compared to warfarin 1.1.7. Patients with poor compliance need individual assessment. Warfarin and rivaroxaban are one daily treatments, rivaroxaban can be put into monitored dosage systems. The twice daily administration of dabigatran could be a disadvantage for patients who find compliance a challenge. 1.1.8. Because NOACs are not monitored, assessment and reinforcement of compliance does not take place. INR monitoring enables assessment of compliance with warfarin. 1.1.9. Dabigatran requires dose adjustment in renal impairment and is contraindicated in severe impairment GFR<30, rivaroxaban is contraindicated if GFR<15ml/min.. Renal function should be checked prior to initiation and monitored annually or more often if any decline is suspected. Warfarin is not contraindicated in renal impairment, although smaller doses are usually given to renally impaired patients. Guideline 313.1 1 of 15 Uncontrolled if printed

1.2. Benefits/advantages of NOACs compared to warfarin 1.2.1. There is no need for INR anticoagulation monitoring. 1.2.2. In the RE-LY trial, dabigatran: 150 mg twice daily reduced the absolute risk of stroke or systemic embolism by 0.6% per year compared to warfarin (1.71% vs. 1.11%; NNT 167). 150 mg twice daily showed a rate of major bleeding similar to warfarin. 110 mg twice daily showed a rate of stroke or systemic embolism similar to warfarin. 110 mg twice daily reduced the absolute risk of major bleeding by 0.7% per year (2.87% vs. 3.57%; NNT 143). Both doses reduced the absolute risk of intracranial bleeding compared to warfarin. ARR 0.44% per year for 150 mg twice daily dose (0.32% vs. 0.76%; NNT 227). 1.2.3 In the Rocket AF multicentre study comparing rivaroxaban to warfarin, rivaroxaban was non-inferior to warfarin for effectiveness Warfarin and rivaroxaban has similar rates of major and non-major bleeding The absolute risk of intracranial bleeding was lower with rivaroxaban compared to warfarin. Risk: 0.5% per year with rivaroxaban and 0.7% per year for warfarin Major GI bleeds were more common with rivaroxaban than with warfarin (3.2% versus 2.2%) Myocardial infarctions (MI) occurred in 101 patients on rivaroxaban but 126 on warfarin. This difference was not statistically significant. 1.2.4. The NOAC effect is not significantly affected by changes in alcohol consumption and diet. 1.2.5. A more stable level of anticoagulation is achieved assuming 100% compliance. 1.2.6. Rapid onset of action (2 to 4 hours after the first dose). Rapid offset of action, therapeutic effect lost within 24 to 48 hours post dose. 1.2.7 In general, drug interactions are less of a clinical problem with NOACs compared to warfarin 1.3. Benefits/advantages of rivaroxaban compared to dabigatran 1.3.1 Rivaroxaban is given only once a day & can be put into monitored dosage systems to assist with compliance 1.3.2 Rivaroxaban can be crushed, making it suitable for patients unable to swallow solid food or being fed by PEG tubing 1.3.3 In MI dabigatran poses an increased risk of a future MI compared with warfarin or rivaroxaban 2. If there is a known history of MI, 1 st consider warfarin. If warfarin is unsuitable rivaroxaban is the preferred NOAC. 1.3.4 Rivaroxaban can be given at an adjusted dose in renal dysfunction where the GFR=15-30ml/minute. Where warfarin is not suitable for this group, rivaroxaban is a possible option (dabigatran is not recommended). 2. CRITERIA FOR USE 2.1. NEW patients generally NOT suitable to start NOACs 2.1.1. History of poor compliance with medication which cannot be improved in the foreseeable future. Serious consideration should be given to whether these patients are suitable for any oral anticoagulation. 2.1.2. Active gastritis is a relative contraindication to dabigatran, GI bleeds were higher with rivaroxaban than warfarin in the Rocket AF trial. Warfarin remains the usual 1 st line choice. 2.1.4. Contraindications to NOACs 2

Severe renal impairment (CrCl <30 ml/min for dabigatran; CrCl< 15ml/min for rivaroxaban; adjust dose if GFR=15 30ml/min). Hepatic impairment (elevated liver enzymes >2 x ULN) or liver disease expected to have any impact on survival. Interacting drugs with dabigatran: Dronedarone, systemic ketoconazole, itraconazole, ciclosporin, and tacrolimus.* * Caution is needed with interacting drugs which require dabigatran dose reduction, e.g. verapamil. Interacting drugs with rivaroxaban Dronedarone, ketoconazole, ritonavir, itraconazole, voriconazole, posaconazole, HIV protease inhibitors, rifampicin, caution with erythromycin and other macrolides. Rivaroxaban affects CYP3A4 and so in theory other interactions are possible but remain unstudied. 2.2. NEW patients generally suitable to start dabigatran 2.2.1. High risk of interactions with warfarin leading to unacceptable INR fluctuations which cannot be addressed 2.2.2. Co-morbidities which make INR control challenging (clinically unstable or medically complex), e.g. unstable severe COPD, uncontrolled LVF, recurrent cellulitis. 2.2.3. Regular INR monitoring is difficult or impractical after exploring all possible alternatives, e.g. immobile patients requiring home visits from phlebotomy 2.2.4. Adherence to variable dosage regimens is likely to be poor, e.g. learning disabilities. 2.2.5. Patients being considered for cardiac ablation. 2.2.6. Secondary prevention of AF patients with recent stroke or TIA to be initiated by a consultant in the secondary care stroke service. Initiated at least 2 weeks after the stroke or TIA when there has been associated brain infarction 2.3. NEW patients generally suitable to start rivaroxaban 2.3.1 Where an individual fits criteria for dabigatran in 2.2 but dabigatran is contraindicated or not suitable. 2.3.3 Where a monitored dosage system or once daily dosing is likely to make the difference with compliance for an individual. Careful individual patient assessment is required. 2.4. EXISTING WARFARIN PATIENTS generally NOT suitable to start NOACs 2.4.1. Good INR control (TTR >70%) - patients should be advised that there is no clear data to support switching to a NOAC in patients with good INR control. There are clear disadvantages/risks associated with NOACs as described above. 2.4.2. Patients taking warfarin for indications other than anticoagulation in AF, due to a lack of clinical trial data in these groups (and unlicensed). In DVT treatment rivaroxaban is licensed for use but due to limited local experience this indication for use is managed by the hospital with all supplies coming from secondary care. 2.4.3. Patients with mitral valve disease or any heart valve replacements (unlicensed in this group even if the patient has co-existing AF). 2.5. EXISTING WARFARIN patients who may be suitable to consider NOAC or warfarin Moderate INR control (TTR 60 to 69%) despite evidence of compliance - patients should be advised that the benefit of switching to a NOAC is unclear. Efforts should be made to find and resolve underlying causes of reduced control. If this proves impossible then a switch to a NOAC e.g. dabigatran may be considered. Dabigatran disadvantages/risks as described above should be discussed. If dabigatran and warfarin both unsuitable then rivaroxaban should be considered. 2.6. EXISTING WARFARIN patients generally suitable to start NOAC 2.6.1. Poor INR control (TTR <60%) despite evidence of compliance. 2.6.2. Allergy to or intolerable side effects from warfarin which would require warfarin withdrawal. 3

2.6.2 Consider rivaroxaban where use of a monitored dosage system compliance aid will help to ensure compliance. Patients should be adequately assessed and other avenues to aid compliance should be actively discussed 3. CONTRAINDICATIONS AND PRECAUTIONS All clinical contraindications to warfarin anticoagulation are also contraindications to NOACs. 3.1. Absolute contraindications to both warfarin and NOACs 3.1.1. Known large oesophageal varices. 3.1.2. Decompensated liver disease, a raised bilirubin (consult if >2 x ULN) or deranged baseline clotting screen (INR >1.5) refer to gastroenterology/hepatology. 3.1.3. Significant thrombocytopenia (platelet count < 50 x 10 9 /L) - refer to haematologist. 3.1.4. Pregnancy or within 48 hours postpartum - usually refer to secondary care for dalteparin under haematological advice. 3.1.5. Within 72 hours of major surgery with risk of severe bleeding - defer and reassess risk post-operatively. 3.1.6. Previously documented severe hypersensitivity reaction to either the drug or excipients consider cardiology opinion. 3.1.7. Acute clinically significant bleed - defer and re-assess stroke versus bleeding risk within 3 months. 3.1.8. Malignant neoplasms. 3.1.9. Recent brain or spinal injury. 3.1.10. Recent brain, spinal or ophthalmic surgery. 3.1.11. Arteriovenous malformation. 3.1.12. Vascular aneurysms. 3.1.13. Major intraspinal or intracerebral vascular anomalies. 3.1.14. Secondary prevention of AF patients with recent stroke or TIA - starting a NOAC will be deferred for 2 weeks after a stroke, sometimes longer after a large stroke. After a TIA the timing will depend on whether there has been associated brain infarction. 3.2. Relative contraindications to both warfarin and NOACs 3.2.1. Previous history intracranial haemorrhage. Some AF patients, especially those considered at higher stroke risk (i.e. CHA 2 DS 2 VAS c score 3), may benefit from antithrombotic therapy, seek the opinion of a stroke specialist. 3.2.2. Major extracranial bleed within the last 6 months where the cause has not been identified or treated decision for oral anti-thrombotic therapy should be deferred. 3.2.3. Documented peptic ulcer within last 3 months decision for oral anti-thrombotic therapy should be deferred until treatment for peptic ulcer completed and for PPI cover. 3.2.4. Recent history of recurrent iatrogenic falls in patient at higher bleeding risk. A risk of falls is not a contraindication to initiating anti-thrombotic therapy. 3.2.5. Higher bleeding risk assessed by patient having 1 or more following risk factors: Age >80 years. Previous history bleed. Low platelet count <100 x 10 9 /L. On concomitant drugs associated with an increased bleeding risk, e.g. SSRIs, oral steroids, NSAIDs, methotrexate or other immunosuppressants. 3.2.6. Dementia or marked cognitive impairment with documented poor medicines compliance and no access to carer support. (Neither warfarin nor dabigatran are recommended to be put into a monitored dosage system, rivaroxaban can be placed in a monitored dosage system device.) 3.2.7. Chronic alcohol abuse especially if associated with binge drinking. 4

4. RESPONSIBILITIES 4.1. Secondary care/specialist responsibilities 4.1.1. Patients must meet local criteria for implementing NICE TA 256 and TA 249 or be approved for PCT funding under the exceptional cases process (ICRP). 4.1.2. The anticoagulant specialist pharmacist will ensure that the patient initiated by the clinic fits local criteria for use. 4.1.3. Dabigatran or rivaroxaban should only be initiated by the new oral anticoagulant (NOAC) specialist pharmacist, or by consultant cardiologist, consultant stroke physician or consultant haematologist if treatment is required urgently (within one week). 4.1.4. A prescription for continuation of a NOAC, once initiated by a specialist listed in 3 above, may be written by any prescriber. 4.1.5. NOACs should not be initiated in the Accident and Emergency department. 4.1.6. Patients initiated by consultant cardiologist, consultant stroke physicians or consultant haematologists will be reviewed in the NOAC clinic as soon as is practical after initiation to ensure they meet local criteria and may be switched to warfarin if they do not. Those initiated during an inpatient stay will be reviewed at a suitable interval post discharge - within a month of the discharge from hospital. 4.1.7. The NOAC specialist pharmacist/consultant cardiologist/consultant stroke physician/consultant haematologist must have an informed discussion with the patient about the risks and benefits of NOACs compared to other anticoagulants. 4.1.8. The NOAC specialist pharmacist or consultant cardiologist/consultant stroke physician/consultant haematologist will write the prescription for the first month of any NOAC. 4.1.9. An audit/nice compliance form completed by the NOAC clinic should clearly document the reasons why the NOAC is being tried, including the time in therapeutic range while on warfarin (if the patient has tried warfarin) and all information required by the PCT for audit purposes (as stated in separate contract document). This will provide ongoing audit information for all patients. 4.1.10. The specialist NOAC pharmacist will contact the patient at, or close to, 2 weeks after initiation (unless inpatient) to assess the tolerability of the drug, and to review if any problems have occurred which can be rectified. 4.1.11. If the NOAC is stopped or changed to an alternative, the GP will be informed in writing in time for them to take appropriate action. This letter will need to be faxed if the review is urgent. 4.1.12. The NOAC clinic will provide advice to GPs (e.g. if side effects occur). 4.1.13. Report all side effects to the MHRA via the yellow card system. 4.1.14. Provide audit data (specified in the contract) to NHS Buckinghamshire until 31 st March 2013. From April 2013 onwards this data will be reported to the Aylesbury Vale and/or Chiltern Clinical Commissioning Groups. 4.2. GP responsibilities 4.2.1. The GP should assess the patient using the locally agreed criteria (above) and refer patients into the specialist service if they feel a new oral anticoagulant agent may be suitable. The referral to the NOAC clinic should state which criteria are met. It is not recommended to refer in patients who are well controlled on warfarin. 4.2.2. The GP should provide recent U&Es and FBC (within the last 3 months). LFTs and INR should also be provided if the GP feels they could be abnormal due to the patient s history. 4.2.3. The GP should provide a patient summary when referring into the NOAC clinic, including time in range for INR if known/relevant, allergies, past medical history, current and past medication over the last 3 to 6 months, alcohol use (if known), recent BP, CHA 2 DS 2 VAS c score and HASBLED score. Forms are available for GP referral (see appendix C) and hospital internal referral (see appendix D). 5

After the 1 st month of treatment provided by the specialist, the GP should: 4.2.4. Continue to prescribe dabigatran or rivaroxaban as indicated. 4.2.5. Undertake ongoing review of the patient to ensure they continue to meet the criteria for anticoagulation and NOACs in particular. This review should include monitoring of renal function, clinical review as indicated by the patient s condition and compliance assessment. 4.2.6. Monitoring as described in 2 above should take place at least annually but more frequently if the patient s clinical condition changes or a reduction in creatinine clearance is suspected. 4.2.7. If a switch to warfarin is appropriate, they will need to be referred into the usual anticoagulant pathway (see section 5.3 on switching from NOAC to warfarin). 4.2.8. This medicine is monitored intensively by the MHRA and CHCM and all adverse reactions should be reported via the yellow card system. 5. DOSAGE (see SPC for more information) Indication Prevention of stroke in patients with nonvalvular AF and with a CHA 2 DS 2 VAS c score of 1 or more 5.1. Missed doses A forgotten rivaroxaban dose may be taken as soon as the patient remembers, on the same day. No double dose should be taken to make up for missed doses. 5.2. Switching from warfarin/dabigatran to rivaroxaban This is undertaken under secondary care supervision. 5.3. Time to response (with rivaroxaban) Full anticoagulation is expected within 2-4 hours of initiation. The half life is 11-13 hours and so its effects will completely wear of in 2 3 days. 6. PRE TREATMENT ASSESSMENT BY GP U&Es and weight, (to allow Creatinine clearance to be calculated) FBC. If the history suggests any likelihood of abnormal LFTs or INR these should also be checked and provided in the referral letter. 7. ONGOING MONITORING SCHEDULE BY GP U&E including assessment of renal function FBC including Hb Dose Re-check stroke versus bleeding risk i.e. CHADSVASC exceeds HASBLED score. Rivaroxaban 20 mg daily is the usual dose If GFR 15-30ml/minute 15mg daily is the recommended dose. Annually, more frequently if patient unwell or declining renal function suspected, e.g. loop diuretic dose needs increasing. Only re-check FBC if anaemia is suspected clinically. Annually but more frequently if clinical status changes. 8. SIDE EFFECTS AND ACTIONS TO BE TAKEN (See SPC for full list) Rivaroxaban is a new drug and is marked in the BNF which signifies intensive monitoring by the MHRA. Please report all suspected side effects through the yellow card system. There is a lack of long term follow up data available. The following table covers the common 6

side effects listed in the SPC. For uncommon and rare effects - see SPC to determine if they could be due to the drug and seek advice if severe. Side Effects Bleeding events like any anticoagulant there is a significant risk of bleeds Anaemia Dizziness, headache, syncope Eye haemorrhage Tachycardia GI upset Rashes Pain in extremeties Fever, peripheral oedema, decreased energy/strength Action See section 10 for management of more severe bleeds. Minor bleeds such as epistaxis may be managed symptomatically. Identify site of blood loss and consider treating as Section 10 advises if severe. May improve with continued therapy Treat symptomatically, seek expert advice Unless clinically worrying does not require action. Exclude haemorrhage. May improve over time. Minor rashes do not warrant treatment discontinuation, but more severe reactions do. An alternative treatment may be required. May be a sign of haemorrhage or may be idiopathic. It is not known if these symptoms are caused by the drug or not but they have been described in association with rivaroxaban 9. NOTABLE DRUG INTERACTIONS (Refer to BNF and SPC) Rivaroxaban affects CYP3A4 & P-gp and is a fairly new medicine. In theory other interactions are possible but many remain unstudied. Dronedarone ketoconazole itraconazole, voriconazole, posaconazole Avoid concomitant use. This drug increases the levels of rivaroxaban and increases the risk of a significant bleed. Avoid concomitant use. These drugs increase the levels of rivaroxaban and increase the risk of a significant bleed. HIV protease inhibitors e.g. ritonavir Caution with erythromycin and other macrolides Phenytoin, phenobarbitone, carbamazepine or St John s wort Rifampicin NSAIDs and antiplatelet agents Avoid concomitant use. These drugs increase the levels of rivaroxaban and increase the risk of a significant bleed. These drugs increase the levels of rivaroxaban to approximately 1.3 fold, caution is recommended, but concomitant use is not contraindicated. Avoid concomitant use. These significantly reduce the levels of rivaroxaban and so reduces its effectiveness. Avoid concomitant use. Rifampicin significantly reduces the levels of rivaroxaban and so reduces its effectiveness. Concomitant use increases the risk of significant GI bleeds. In the Rocket AF trial many patients were given low dose aspirin concomitantly for co-existing conditions. 7

10. MANAGEMENT OF OVERDOSE AND BLEEDING Dabigatran (Pradaxa ) is a direct thrombin inhibitor with a half-life of 12-14 hours. Rivaroxaban is a direct Factor Xa inhibitor with a half-life of 11 13 hours. Dabigatran is primarily excreted renally and the half-life is prolonged in renal impairment. Rivaroxaban is partly metabolised to inactive forms in the liver and partly excreted renally. The half life of both drugs is prolonged in renal impairment, though to a lesser extent with rivaroxaban than with dabigatran. The major adverse effect of all anticoagulant medications is bleeding. All patients Check coagulation screen indicating time of last NOAC dose when requesting test. dabigatran aptt Moderately sensitive to dabigatran, but non-linear at high levels. Thrombin time (TT) Very sensitive to the presence of dabigatran. A normal result excludes the presence of significant levels of the drug. Prothrombin Time Not sensitive to dabigatran - a (PT/INR) high result suggests overdose of a different anticoagulant such as warfarin. rivaroxaban Moderately sensitive to rivaroxaban, but not the most useful marker Not sensitive to the presence of rivaroxaban. Sensitive to rivaroxaban. High result expected with either rivaroxaban or warfarin excess Fibrinogen May be low - very variable! Variable response Check full blood count, renal function and electrolytes (including calcium). No bleeding or minor bleeding 1. Omit NOAC until the bleeding stops, unless the risk of thrombosis is very high. 2. Local measures may be helpful. 3. Consider cause of bleeding. 4. For oral cavity bleeding also consider tranexamic acid 250 mg/5 ml mouthwash 5 to 10 ml 8 hourly. (Unlicensed) Major/life-threatening haemorrhage (e.g. CNS/major GI) 1. Urgent admission to hospital is required - Hospital clinicians see guideline 34 Guideline 34 Dabigatran: Guidance for Management of Overdose and Bleeding 8

11. BACK-UP INFORMATION/ADVICE New Oral Anticoagulant (NOAC) Service Cardiology Haematology Stroke Specialists Hospital Pharmacy - Medicines Information Wycombe and Amersham Hospitals Contact Details Stoke Mandeville Hospital Satinder Bhandal, Head of NOAC Service and VTE Lead Pharmacist satinder.bhandal@buckshealthcare.nhs.uk Fax: 01494 425011 Dr Piers Clifford piers.clifford@buckshealthcare.nhs.uk 01494 425004 Fax: 01494 425908 01494 425224 (secretaries) In an emergency contact Consultant Haematologist on-call 01494 526161 Dr Matthew Burn matthew.burn@buckshealthcare.nhs.uk 01494 425908 Dr Amulya Misra amulya.misra@buckshealthcare.nhs.uk 01494 426302 01296 316197 01296 316197 Switchboards Amersham: 01494 434411 Wycombe: 01494 526161 12. REFERENCES Dr Andrew Money-Kyrle andrew.moneykyrle@buckshealthcare.nhs.uk 01296 315543 Dr Punit Ramrakha punit.ramrakha@buckshealthcare.nhs.uk 01296 315675 Fax: 01296 315672 01296 315516 (leave message for Consultant call back) In an emergency contact Consultant Haematologist on-call 01296 315000 Dr Chris Durkin chris.durkin@buckshealthcare.nhs.uk 01296 316542 Dr Dennis Briley dennis.briley@buckshealthcare.nhs.uk 01296 315688 01296 315000 1. Dabigatran for the prevention of stroke or systemic embolism in AF (NICE TA 249) March 2012. Available at www.nice.org.uk <accessed 30/8/12> 2. Connolly-SJ et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation (Re-LY study). N Engl J Med 2009; 361:1139-115. http://www.nejm.org/doi/full/10.1056/nejmoa0905561 3. SPC for Pradaxa 150mg and 100mg strengths www.medicines.org.uk last updated Aug 2012 <accessed 6/08/12> 4. Rivaroxaban for the prevention of stroke and systemic embolism in people with AF (NICE TA 256) May 2012. Available at www.nice.org.uk <accessed 30/10/12> 5. Patel-M et al Rivaroxaban versus warfarin in Nonvalvular AF (Rocket AF) New Engl J Med Sept 20122: 365: 863-891 6. SPC for Xarelto 20 mg & 15mg strengths. Available at www.medicines.org.uk last updated May 2012 <accessed 6/11/12> 7. Kanaka KA, Szlam F, J Thromb Haemost 2010; 8: 2589-91 9

Appendices Appendix B: Care Pathways: i) New AF Patient from Primary Care ii) Patients Initiated on Dabigatran by Buckinghamshire Healthcare NHS Trust (BHNHST) iii) Existing Patients on Warfarin Appendix C: Referral Form 1 - GP to NOAC Clinic Appendix D: Referral Form 2 - Hospital AF referrals to NOAC Clinic Title of Guideline Rivaroxaban for Atrial Fibrillation - Amber Initiation Guideline Guideline Number Version 1.5 Effective Date Dec 2012 Review Date Dec 2014 Original Version Produced Dec 2012 Approvals: Formulary Management Group Dec 2012 Clinical Guidelines Subgroup Area Prescribing Committee Feb 2013 Author/s Sarah Crotty, Interface Pharmacist, NHS Buckinghamshire, Satinder Bhandal, Maire Stapleton (Senior Pharmacists BHNHST) Dr Jonathan Pattinson, Consultant Haematologist SDU(s)/Department(s) responsible Pharmacy (Primary and Secondary Care) for updating the guideline Haematology Uploaded to Intranet 10

Appendix A: Care Pathways i) New AF Patient from Primary Care GP diagnoses patient with AF and refers to NOAC service NOAC clinic decides on anticoagulation option for patient in line with Bucks criteria Start warfarin treatment, provide prescription, counsel patient, provide anticoagulation therapy pack Start dabigatran provide prescription, counsel patient, provide Anticoagulant Alert Card Letter to GP If warfarin and dabigatran unsuitable, consider rivaroxaban or referral Refer into usual warfarin anticoagulant clinic for patients from that GP practice Second patient contact by NOAC clinic usually by phone at 2 weeks: Address issues/concerns Highlight importance of compliance Discharge to care of GP for ongoing anticoagulation with dabigatran If NOAC not to be continued inform GP If patient needs to be switched to warfarin, refer into usual anticoagulation clinic for patients from that GP practice Guideline 313.1 11 of 15 Uncontrolled if printed

ii) Patients initiated on a NOAC by BHT Consultant cardiologist/stroke physician or haematologist identifies patient potentially requiring NOAC as inpatient or outpatient Initiation not urgent: refer to NOAC service Initiation urgent (within 1 week): Consultant prescribes NOAC Patient referred to NOAC service NOAC clinic decides/reviews anticoagulation options for patient in line with Bucks criteria Start warfarin treatment, provide prescription, counsel patient, provide anticoagulation therapy pack Start/continue dabigatran, provide prescription if necessary, counsel patient, provide Anticoagulant Alert Card Letter to GP If warfarin and dabigatran unsuitable, consider rivaroxaban or referral Refer into usual warfarin anticoagulant clinic for patients from that GP practice Second patient contact by NOAC clinic usually by phone at 2 weeks: Address issues/concerns Highlight importance of compliance Discharge to care of GP for ongoing anticoagulation with NOAC If NOAC not to be continued inform GP If patient needs to be switched to warfarin refer into usual anticoagulation clinic for patients from that GP practice 12

iii) Anticoagulation Pathway for Existing Patients on Warfarin Warfarin anticoagulant clinic identifies patient with poor INR control. If patient is not being seen by clinical staff (postal system) then a standard letter will be sent to ask the GP to consider referring to NOAC clinic If being seen by an anticoagulant nurse or doctor they should refer the patient to the NOAC clinic directly and inform the GP. GP/anticoagulant clinician (as appropriate) refers to NOAC clinic if patient potentially meets Bucks criteria for NOAC NOAC clinic decides on anticoagulation option for patient in line with Bucks criteria Continue warfarin after counselling Start dabigatran, provide prescription, counsel patient, provide Anticoagulation Alert Card Letter to GP If warfarin and dabigatran unsuitable, consider rivaroxaban or referral Second patient contact by NOAC clinic usually by phone at 2 weeks: Address issues/concerns Highlight importance of compliance Discharge to care of GP for ongoing anticoagulation with NOAC If NOAC not to be continued inform GP If patient needs to be switched to warfarin refer into usual anticoagulation clinic for patients from the GP practice 13

Appendix B: Referral Form 1 GP to NOAC Clinic Patient name: DoB: Sex: NHS No: Address: GP Referral to New Oral Anticoagulant Service at BHNHST GP Name: Address: Postcode: Tel (day): Tel (mobile): Patient email: Patient requires transport: Patient needs interpreter: Language: Ethnicity: Date of referral: Postcode: Practice code: Tel: Fax: Reason for referral: On warfarin Time in range OR warfarin naive Renal function info must be supplied: Date creatinine and weight kg Known history of poor compliance? Give details In addition please provide a Patient Summary which details: Allergies, PMH, current medication and recent past medication, alcohol use if known, recent BP, FBC LFTs and INR (if any reason to suspect may be abnormal from history) Please ring the scores for your patient: Points Clinical Characteristic Points C LVF/LVD dysfunction 1 H Hypertension 1 H Hypertension 1 A Renal or LFTs abnormal 1 or 2 A 2 >75 years 2 S Stroke 1 D Diabetes mellitus 1 B Bleeding 1 S 2 Prior stroke or TIA 2 L Labile INRs 1 V Vascular disease 1 E >65 years 1 A Age 64 74 1 D Drugs or alcohol >8 U/week 1 or 2 Sc Female 1 Total Total Signed... (GP) Preferred clinic: Amersham Wycombe Stoke Mandeville (please ring) FAX ALL REFERALS TO: 01494 425 011 TELEPHONE NUMBER: 077 857 08 391 14

Appendix C: Referral Form 2 Hospital AF Referrals to NOAC Clinic Hospital AF Referrals to New Oral Anticoagulant (NOAC) Clinic Addressograph or Name/Address/MRN/DOB/NHS No. Telephone Mobile Consultant Outpatient Clinic or Ward Name of referrer Bleep Signature Date Hospital Dear NOAC Pharmacist, Please prescribe and monitor anticoagulant therapy as appropriate in line with Bucks PCT/BHNHST criteria for: Uncomplicated AF / AF for cardioversion / AF for ablation / AF and TIA or stroke (circle) If warfarin has already been started give details Date INR Dose For warfarin target INR of 2 3. Delete if other range required state alternative and reason for change NOACs will be started in those patients fitting Bucks PCT/BHNHST criteria by the NOAC Clinic. If your patient needs to start a NOAC whilst an inpatient or within 7 days of discharge then refer to a Consultant Cardiologist/Consultant Haematologist or Consultant Stroke Physician for initiation. If a NOAC is started, state: Drug name and dose. Date. Name of Consultant issuing 1 st prescription. BLOODS WITHIN LAST 2 WEEKS NB: If unavailable, they must be requested. Referral cannot be accepted without them. Blood Test Creatinine Platelets Baseline INR LFTs normal Y/N Date checked Comments that would impact on anticoagulation Please circle the scores for your patient: Points Clinical Characteristic Points C LVF/LVD dysfunction 1 H Hypertension 1 H Hypertension 1 A Renal or LFTs abnormal 1 or 2 A 2 >75 years 2 S Stroke 1 D Diabetes mellitus 1 B Bleeding 1 S 2 Prior stroke or TIA 2 L Labile INRs 1 V Vascular disease 1 E >65 years 1 A Age 64 74 1 D Drugs or alcohol >8 U/week 1 or 2 Sc Female 1 Total Total Preferred clinic: Amersham Wycombe Stoke Mandeville Fax all referrals to: 01494 425 011 15