HERTFORDSHIRE MEDICINES MANAGEMENT COMMITTEE (HMMC) DABIGATRAN RECOMMENDED What it is Indications Date decision last revised

Transcription

1 Name: generic (trade) Dabigatran etexilate (Pradaxa ) HERTFORDSHIRE MEDICINES MANAGEMENT COMMITTEE (HMMC) DABIGATRAN RECOMMENDED What it is Indications Date decision last revised Direct thrombin inhibitor See below July 203 (update of July 202 HMMC recommendation) Decision status NICE guidance Final NICE TA 57, recommended NICE TA 249, recommended Licensed Indications Dabigatran etexilate is an orally active antithrombotic agent and holds a UK marketing authorisation for: the primary prevention of venous thromboembolic events in adult patients who have undergone elective total hip replacement surgery or total knee replacement surgery, AND the prevention of venous thromboembolic events in adult patients with atrial fibrillation (AF). DABIGATRAN FOR USE IN PATIENTS UNDERGOING HIP AND KNEE REPLACEMENT Dabigatran for primary prevention of venous thromboembolic events in patients who have had a hip or knee operation is included within the tariff price for the procedure. GPs should NOT prescribe dabigatran for this indication. DABIGATRAN FOR USE IN PATIENTS WITH NON VALVULAR ATRIAL FIBRILLATION Recommended for primary or secondary care prescribing for non valvular atrial fibrillation in line with algorithm. Supporting documents are available to assist in the anticoagulant decision making process, highlighting the benefits and risks of the various treatment options to support clinician/patient discussions: Full guidance NOACs in non-valvular AF Algorithm for anticoagulant choice in non-valvular AF Comparison of NOACs and warfarin Patient agreement for NOACs Anticoagulant choice for atrial fibrillation patient information Template letter from specialist to primary care following initiation of dabigatran for stroke prevention in AF All patients with AF must have a CHADS 2 score documented, and bleeding risk assessment. NICE recommendation, TA249 Dabigatran etexilate is recommended as an option for the prevention of stroke and systemic embolism within its licensed indication, that is, in people with nonvalvular atrial fibrillation with one or more of the following risk factors: o previous stroke, transient ischaemic attack or systemic embolism o left ventricular ejection fraction below 40% o symptomatic heart failure of New York Heart Association (NYHA) class 2 or above o o age 75 years or older age 65 years or older with one of the following: diabetes mellitus, coronary artery disease or hypertension. The decision about whether to start treatment with dabigatran etexilate should be made after an informed discussion between the clinician and the person about the risks and benefits of dabigatran etexilate compared with warfarin. For people who are taking warfarin, the potential risks and benefits of switching to dabigatran etexilate should be considered in light of their level of international normalised ratio (INR) control. References: NICE TA57: Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults, June 20, NICE TA249: Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation, March 202, Produced by Hertfordshire Pharmacy and Medicines Optimisation Team Hertfordshire, Bedfordshire and Luton Commissioning Support Central Eastern Commissioning Support Unit This HMMC recommendation is based upon the evidence available at the time of publication. The recommendation will be reviewed upon request in the light of new evidence becoming available.

2 Algorithm for the use of Warfarin and vel Oral Anticoagulants (NOACs) for nonvalvular Atrial Fibrillation Algorithm adapted from Health Improvement Board Scotland On balance of risks and benefits, warfarin remains the anticoagulant of choice for moderate or high risk atrial fibrillation patients Is the patient currently taking warfarin? (Existing patient) Is the patient complying with their warfarin regimen? (Assess after 3 months of therapy) Make efforts to improve compliance. If non-compliance** is still a concern assess risk and consider stopping. If warfarin is stopped due to intolerable side effects, consider NOAC. New patient Does the patient with nonvalvular atrial fibrillation have a CHADS 2 2? Review the individual patient and their stroke (CHADS 2 ) and bleeding risk (HAS-BLED). Have risk and benefits of treatments been discussed with patient? Does the patient have good INR control (determined by clinical judgement, no extreme INR variations or time in treatment range [TTR] > 65% [where INR monitoring software is available])? Is warfarin tolerated? Aspirin to be considered for patients with CHADS 2 score of 0-, unless cardiologist gives rationale for anticoagulation Prescribe in line with patient selection criteria (page 4) Continue on warfarin Consider prescribing apixaban, dabigatran or rivaroxaban in patients: With poor INR control despite evidence that they are complying to treatment With intolerance to warfarin NB: All anticoagulants increase the risk of bleeding ** n- compliance: n-compliance with warfarin is not an indication for initiating therapy with NOACs. Many of the causes of non-compliance with warfarin may also result in non-compliance with NOACs, e.g. alcoholism, chaotic lifestyle, wilful non-compliance. Regular clinical review of patients on NOACs is very important especially as such patients will not be monitored routinely. See prescribing guidance with respect to monitoring BMJ learning modules on anti-coagulation warfarin &page=0 warfarin &page=0

3 Choice of appropriate anticoagulant The decision about whether to start treatment with a NOAC should be made after an informed discussion between the clinician and the patient about the risks and benefits of anticoagulants, and in particular NOACs compared with warfarin. For people who are taking warfarin, the potential risks and benefits of switching to a NOAC should be considered in light of their level of international normalised ratio (INR) control. Individual stroke risk and bleeding risk must be assessed using the CHADS 2 and HASBLED CHADS 2 scoring system HAS-BLED bleeding risk score Risk Factor Score if Risk Factor Score present Congestive heart failure (C ) Uncontrolled hypertension (systolic > 60mmHg, unresponsive to anti-hypertensives) Hypertension (H) Renal disease (dialysis, transplant, Cr>2.3mg/dl or > 200 umol/l) Age 75yrs (A) Liver disease? (cirrhosis; bilirubin >2xnormal in association with AST/ALT/ALP >3x normal) Diabetes mellitus (D) Previous history of stroke Prior stroke or TIA (S 2) 2 Prior major bleeding (anaemia or predisposition to bleeding? Total Score: Age 65 Medication usage predisposing to bleeding? (anti-platelets, NSAIDs,etc) Alcohol intake (consuming 8 or more alcoholic drinks per week) Labile INRs (refers to unstable INRs/ high INRs or poor time in NB: Where HAS-BLED score is high, prescribers therapeutic range (e.g. TTR<60%). may want to seek guidance from specialists on Total score whether anticoagulation is in the best interest of the patient. A HAS-BLED score of >3 indicates an increased one-year bleed risk on anticoagulation which would be sufficient to justify caution or more frequent evaluation. Where a patient scores point for labile INR, a score of >4 would indicate a need for caution. Interpretation of stroke risk using CHADS 2 score Interpretation of bleeding risk using HAS-BLED score CHADS 2 score Annual stroke rate (%) HAS-BLED score Bleeds/00 patients

4 . Patients with non-valvular atrial fibrillation who meet the criteria for anticoagulation but are currently not anticoagulated (i.e. newly diagnosed patients or existing patients in whom an oral anticoagulant is indicated but not currently prescribed). Where the bleeding risk is higher (using HASBLED) than the stroke rate, do not start anticoagulation without first consulting a specialist. WARFARIN REMAINS A SUITABLE FIRST-LINE ORAL ANTICOAGULANT FOR MOST PATIENTS... Warfarin is the only option in patients: with CrCl < 5ml/min or other absolute contraindications to NOAC. te that: Dabigatran is contra-indicated at CrCl <30ml/min Rivaroxaban is contra-indicated at CrCl <5ml/min, AND Rivaroxaban dose should be reduced to 5mg once daily at CrCl 5-49ml/min Apixaban is contra-indicated at CrCl<5ml/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.5 mg/dl (33 micromol/l). Patients with creatinine clearance 5-29 ml/min should also receive the lower dose of apixaban 2.5 mg twice daily...2 Warfarin may be the preferred option in patients: with CrCl < 30 ml/min (NB Patients with a baseline CrCl of ml/min are at risk or progressive/acute renal dysfunction and the potential risks of bleeding with NOACs should be weighed on an individual basis) with a history of significant peptic ulcer disease significant ischaemic heart disease in absence of other determining considerations Where a specialist advises a NOAC in these categories a clear rationale will be provided...3 A NOAC may be the preferred initial option in patients: predicted to be difficult to maintain in therapeutic range on warfarin because of the need for recurrent need for interacting medications e.g. recurrent antibiotics with known excess use of ethanol (NB: patient compliance to treatment must be checked) who require domiciliary testing with a very high risk of stroke e.g. CHADS 2 score of 3 or more where rapid anticoagulation is considered clinically necessary by specialists (except where.. applies - where warfarin is the only choice; or..2 applies, where warfarin is the preferred choice). NB: Risk versus the benefit must be discussed with patients and clear rationale given to GPs In patients whose relative stroke risk is the same as their bleeding risk (using HASBLED score) dabigatran 0mg bd dosing or apixaban could be considered...4. A NOAC is the preferred option in patients: with a known sensitivity or serious side effect with warfarin which has lead to discontinuation in the past. in whom resistance to warfarin therapy has been shown in the past (inability to get INR into therapeutic range despite high doses of warfarin) which has lead to warfarin discontinuation Warfarin is recommended as the first line treatment in all other patients. The discussion with the patient should include the following factors, to explain why this decision is being made on the grounds of safety as well as cost effectiveness: lack of long term data on NOACs issues concerning reversibility NICE guidance and evidence base for apixaban/dabigatran /rivaroxaban non-compliance in clinical trial setting and its implications for those not in trials principles used in patient selection patient will be converted to NOAC if TTR < 65% after 3 months in presence of compliance higher cost of NOACs

5 ..6 When patient is referred from cardiology department with planned cardioversion Dabigatran will be initiated by a cardiologist. There is currently no data on apixaban or rivaroxaban in cardioversion. Clear advice on dose and duration of treatment will be provided to the GP. Anticoagulant service will see patient within 5 working days to perform counselling, registration etc (as above) Dabigatran should be given for 4 weeks before cardioversion and be continued for 4 weeks after cardioversion. Patients will be reviewed in cardiology outpatient department 4-6 weeks post cardioversion. It is recommended that further anticoagulant choice, if cardioversion fails, is in line with these guidelines..2 Existing patients taking warfarin for non-valvular atrial fibrillation WARFARIN REMAINS A SUITABLE FIRST-LINE ORAL ANTICOAGULANT FOR MOST PATIENTS..2. Conversion to NOAC recommended for patients: intolerant of vitamin K antagonists (VKA) resistant to the effects of warfarin (failure to get into the therapeutic range despite dose escalation) TTR < 65% after > 3 months (despite good compliance with warfarin).2.2 Conversion to NOAC may be considered for patients: with history of significant bleed on warfarin (dabigatran 0mg bd or apixaban) requiring domiciliary phlebotomy.2.3 Conversion to dabigatran 50mg bd or apixaban* may be considered in patients with history of stroke or TIA in the last 3 months, whilst taking warfarin despite good compliance, after assessing bleeding risk in relation to stroke risk. * Dabigatran 50mg bd and apixaban have been shown in clinical trials to reduce stroke risk more than warfarin. This additional benefit is dependent upon the degree of INR control in the warfarin group..2.4 Other patients who are well controlled and tolerant of warfarin are NOT recommended to change