Anticoagulation. Therapeutics. Aims. Learning Outcomes. AF Prevalence. Symptoms of AF. AF is the most common heart rhythm disturbance 1

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1 Aims Anticoagulation K A T H E R I N E S T I R L I N G C O N S U L T A N T P H A R M A C I S T A N T I C O A G U L A T I O N A N D T H R O M B O S I S L E E D S T E A C H I N G H O S P I T A L S The aim of this session is to discuss how community pharmacists can help make anticoagulation safer for their patients Learning Outcomes The learning outcomes of the session will be: 1. To understand the warfarin patient pathway and how you can contribute to safety as per the NPSA Safety Alert 2. To understand the use of anticoagulation in stroke prevention in AF 3. To know how the NMS and MURs can be used for patients on anticoagulation Therapeutics AF Prevalence AF is the most common heart rhythm disturbance 1 It is estimated that lifetime risk for developing AF is 1 in 4 at age 40 years and older 1 NICE Prevalence of AF roughly doubles with each advancing decade of age, 0.5% at 50-59yrs to almost 9% at 80-89yrs 4 Due to the aging population, the number of patients with AF is expected to double within 30 years 3 Symptoms of AF If sustained AF: Palpitations +/- chest pain Dyspnoea +/- dizziness Reduced exercise tolerance (often significant) Panic attacks/agoraphobia/depression If Paroxysmal: As above, but may be more severe (less well tolerated) Often preceded by exertion, thump in the chest, fatigue, alcohol, coffee and other stimulants NONE! 1. Lloyd-Jones DM, et al. Circulation 2004;110: ; 2. Decision Resources. Atrial Fibrillation Report. Dec 2008; 3. Go AS, et al. JAMA 2001;285: Date of preparation: October 2012 Weert, H. Diagnosing atrial fibrillation in general practice. BMJ 2007; 335: Date of preparation: October

2 AF and Stroke CHADS2 Stroke risk assessment Cardioembolic stroke is the main complication of AF 1 Approx 12,500 strokes a year are attributable to AF in England 2 Risk of stroke is the same in paroxysmal or sustained AF 3 Cardioembolic stroke has a 30-day mortality of 25% 5 Date of preparation: October 2012 Condition Points C Congestive heart Failure 1 H Hypertension 1 A Age (>75) 1 D Diabetes 1 S 2 Stroke or TIA previously 2 CHADS 2 Score Stroke risk % 95% CI 0 1.9% % % % % % % Wolf PA, et al. Stroke 1991;22: ; Hart RG, et al. J Am Coll Cardiol 2000;35: ; 4. National Collaborating Centre for Chronic Conditions. AF. Royal college of Physicians, Lin H-J, et al. Stroke 1996; 27: Gage et al. JAMA 2001; 285 (22): Date of preparation: October 2012 CHA 2 DS 2 Vasc 1 point for Congestive heart failure Hypertension Diabetes Vascular disease Age Female 2 points for Previous stroke / TIA Age > 75 CHA 2 DS 2 VASc CHADSVASC clinical risk estimation. Adapted from Lips et al. CHA 2 DS 2 VASc ADJUSTED STROKE SCORE RATE (% year) 0 0% 1 1,3% 2 2,2% 3 3,2% 4 4,0% 5 6,7% 6 9,8% 7 9,6%** 8 6,7%** 9 15,2% HASBLED GRASP AF HASBLED clinical characteristic [click on present risk factors] POINTS CLINICAL CHARACTERISTIC AWARDED Hypertension Uncontrolled, > 160 mmhg systolic Abnormal liver function 1 Abnormal renal function 1 Stroke Previous history, particularly lacunar 1 1 Bleeding history or predisposition (anemia) 1 Labile INRs Therapeutic time in range < 60% 1 Elderly (Age >65) 1 Drugs Antiplatelet agents or NSAIDs 1 Alcohol use 8u / week 1 Date of preparation: October 2012 GRASP AF TOOLKIT Guidance on Risk Assessment & Stroke Prevention for Atrial Fibrillation West Yorkshire Cardiovascular Network doc p8 2

3 Mechanism of action of Anticoagulants Apixaban Treatment of DVT and PE and prevention of recurrence Stroke prevention in AF Prevention of stroke in patients with metal mechanical valves Coagulation disorders such as antiphospholipid syndrome, protein C deficiency Other venous coagulation disorders e.g. portal vein thrombosis, radial vein thrombosis Australian Prescriber April 2010 Target Ranges Challenges to Vitamin K antagonists BSCH guidance suggests DVT/PE first episode or recurrence off anticoagulation 2.5 (range 2-3) DVT/PE when INR therapeutic 3.5 (range 3-4) Antiphospholipid syndrome 2.5 (range 2-3) Unpredictable response Narrow therapeutic window (INR range 2-3) VKA therapy has several limitations that make it difficult to use in practice Frequent dose adjustments Numerous food-drug interactions Stroke prevention in AF 2.5 (range 2-3) Cardioversion 3 (range ) before cardioversion 2.5 (range 2-3) after cardioversion Prosthetic valves 2.5 (range 2-3), 3.0 (range ) or 3.5 (range 3 4) depending on type and position Routine coagulation monitoring Slow onset/offset of action Numerous drug-drug interactions resistance Ansell J et al. Chest 2008;133;160S-198S Date of preparation: October 2012 Drug Interactions NPSA How do you handle A repeat prescription for warfarin and an acute prescription for amoxicillin 500mg tds for 7 days? Promote safe practice for prescribers co-prescribing one or more clinically significant interacting medicines for patients already on oral anticoagulants: arrange for additional INR blood tests and inform the anticoagulant service that an interacting medicine has been prescribed. 3

4 and Antibiotics Antibiotics can affect warfarin in a number of ways: Affect on vitamin K-producing intestinal flora may increase INR after a few days. Inhibition or induction of CYP450 isoenzymes responsible for metabolism (CYP3A4, CYP1A2, CYP2C9) Recommend recheck INR after 3-5 days of concomitant antibiotic, patient to contact anticoagulant service or GP Shouldn t preclude use of antibiotic, just needs careful monitoring How do you handle Drug Interactions An acute prescription for miconazole oral gel in a known warfarin patient and Miconazole Oral Gel Interactions Miconazole oral gel will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism Have had patients with INR > 8 on the combination Use alternative i.e. nystatin How do you handle A request for a multivitamin supplement in a warfarin patient Interactions Monitoring Multivitamins can be used with warfarin but ensure no vitamin K in the product. Ask the patient to let the anticoagulant service know what they ve started. Many herbal medicines can increase the risk of bleeding, if in doubt use your local medicines information centre to check if a product is suitable How do you handle A prescription for warfarin in a patient who says they haven t had their INR checked for over 5 weeks/8 weeks/12 weeks 4

5 NPSA Monitoring Promote safe practice for prescribers and pharmacists to check that patients blood clotting (International Normalised Ratio, INR) is monitored regularly and that the INR level is safe before issuing or dispensing repeat prescriptions for oral anticoagulants. On initiation of warfarin patients may be seen daily. Once stabilised the time between appointments can be increased, usually dictated by dosing software (DAWN, RAT, INR-STAR) The maximum recommended time between appointments is 12 weeks (NPSA) Check when a patients next appointment is. If they haven t had a check for over 12 weeks and no check is booked discuss with GP as may be safer not to dispense and MDS and MDS A patient brings in a prescription for warfarin 0.5mg and 5mg tablets and asks for them to go into her MDS. What do you need to discuss with them? Not usually a safe combination. Many multiples have strict guidance against. If there are no other options ensure you discuss with the anticoagulant service, they fax you any dose changes, you know when the patient has an appointment and you record all doses, INRs and appointments on a PMR. You have a system in place to urgently retrieve the MDS if the warfarin needs to be omitted and to change the MDS if the dose changes. Local Commissioning CCGs Safety Section TJ 5

6 Practical Advice for NMS/MUR We have had patients who have continued taking their warfarin without monitoring for over a year. Some have been lucky and are still in their therapeutic range, Some are subtherapeutic and have recurrent DVT/PE or stroke Some are admitted with bleeding due to high INRs some had stockpiled tablets We have had some patients who have confused the strength and colour of their tablets and had dangerously high, or low INRs One patient with repeated INRs > 8 still had a therapeutic INR after we had stopped warfarin. Her son had put warfarin in an atenolol packet and was filling her weekly medi-dose with warfarin thinking it was atenolol A new patient presents with a prescription for warfarin 0.5mg, 1mg, 3mg and 5mg tablets. What questions do you need to ask to ensure this is safe to dispense? NPSA Promote safe practice for prescribers and pharmacists to check that patients blood clotting (International Normalised Ratio, INR) is monitored regularly and that the INR level is safe before issuing or dispensing repeat prescriptions for oral anticoagulants. Ask their current dose or ask to see their clinic letter or warfarin booklet (depending on area). Record dose, INR and last appointment eg on PMR Ask if they know the colours and strengths of their usual tablets. Check if they have an anticoagulant card and have written information If not refer to local clinic or they can find an online copy from the NPSA website English - Oral anticoagulant therapy patient information booklet this is available in other languages to download 6

7 Problems and Food Ensure doses are in mg and not number of tablets Ensure all staff caring for patients on anticoagulants have necessary work competencies (incl pharmacists, dispensers, technicians and counter assisstants) Workforce competence statements and elearning available It says in my yellow book I can t drink cranberry juice or eat broccoli, what else can t I eat? and Food and Pregnancy Cranberry juice should be avoided as has been shown to increase the INR Broccoli, other green leafy vegetables and other foods that contain vitamin K are all fine to be eaten in moderation as part of a healthy well balanced diet Alcohol should be kept to healthy limits and no binge drinking A known warfarin patient comes in to buy a pregnancy test, what would you advise? and Pregnancy should be avoided in pregnancy as it is a teratogen, crosses the placenta and can cause fetal bleeding and malformations (fetal warfarin syndrome). Most Ante-natal clinics will have offer pre-pregnancy counselling for women on warfarin who want to become pregnant. is safe to take while breast feeding NMS and Anticoagulants for stroke prevention in AF 7

8 NMS News Reports PSNC and NHS Employers envisaged that the successful implementation of NMS would: improve patient adherence which will generally lead to better health outcomes increase patient engagement with their condition and medicines, supporting patients in making decisions about their treatment and self-management reduce medicines wastage reduce hospital admissions due to adverse events from medicines lead to increased Yellow Card reporting of adverse reactions to medicines by pharmacists and patients, thereby supporting improved pharmacovigilance receive positive assessment from patients At last: an alternative to taking rat poison, The side effects of blood thinner warfarin bring misery to thousands but now there s another option No more rat poison: New stroke drug is better than warfarin RE-LY ROCKET - AF DRUG Ischaemic stroke ICH Other DRUG Stroke Bleeding ICH 1.20%/yr 0.38%/yr Unblinded 2.20%/yr 14.5%/yr 0.7% Dabigatran 110mg 1.34%/yr 0.10%/yr Rivaroxaban 1.7%/yr 14.9%/yr 0.5% Dabigatran 150mg 0.92%/yr 0.12%/yr MI GI bleeds ARISTOTLE New Oral Anticoagulants DRUG All stroke ICH Major bleeding 1.6%/yr 0.47%/yr 3.09%/yr Apixaban 2.5mg or 5mg bd 1.27%/yr 0.24%/yr 2.13%/yr Apixaban, Rivaroxaban and Dabigatran all licensed for stroke prevention in non-valvular AF Rivaroxaban 20mg or 15mg od Apixaban 5mg or 2.5mg bd Dabigatran 150mg bd or 110mg bd 8

9 Counselling Information Why are they taking an anticoagulant Explain stroke prevention, risk of stroke i.e. number of people out of 100 who would have a stroke without anticoagulation Importance of taking regularly to ensure anticoagulated continuously Counselling Information How to take Dabigatran swallow whole with a glass of water, absorption increased if capsules opened, store in original pack, foil hard to open so peel back rather than pushing through Rivaroxaban and apixaban swallow whole but can be crushed and put down an NG/PEG Counselling Information What to do if a dose is missed Remember short half lives compared to warfarin, increases risk of stroke Rivaroxaban once daily, take up to 12 hours after dose due Apixaban and dabigatran bd dosing, take up to 6 hours after dose due If later omit dose and take next dose as usual Bleeding risk Counselling Information All are anticoagulants so they can cause bleeding If a patient has bleeding contra-indications to warfarin the new agents are very likely to be contra-indicated Bruising/epistaxis/haematuria/GI bleeding all common Minor bleeding or malaena report to GP immediately Major bleeding (lasting > 10 minutes), head injury, major trauma or fall A&E No reversal agent Alert cards Counselling Information Available from each company Use yellow warfarin cards as instantly recognisable Adverse effects Dabigatran twice as much dyspepsia and GI bleeding than warfarin, can cause diarrhoea Rivaroxaban less dyspepsia and GI bleeding than dabigatran but still common, can cause constipation, dizziness, headaches and general weakness. More epistaxis and haematuria than with warfarin Apixaban similar effects to rivaroxaban but less GI bleeding or dyspepsia than dabigatran or rivaroxaban Interactions Counselling Information Rivaroxaban and apixaban interact with strong inhibitors or inducers of CYP3A4 or P-glycoprotein e.g. erythromycin, clarithromycin, fluconazole inhibitors, increase risk of bleeding E.g phenytoin, carbamazepine inducers, may decrease levels Dabigatran interacts with P-glycoprotein inhibitors or inducers, E.g. amiodarone, verapamil may want to use lower dose, clarithromycin increases risk of bleeding Poor bioavailability so interacting drugs can cause big changes in drug levels 9

10 Counselling Information Summary Care with drugs than can increase bleeding eg aspirin, NSAIDs, omega 3 fatty acids, garlic, SSRIs Not to be used if pregnant or breast feeding Dabigatran contains sunset yellow reports of allergy Dabigatran is not stable in a MDS Rivaroxaban and apixaban can both go into a MDS Food and alcohol No food issues with NOACs Moderate alcohol only as can increase risk of bleeding and gastric irritation Check INR, dose and appointment before dispensing warfarin and document on PMR Ensure patients are aware of colours and strengths of tablets Ensure patients started on interacting drugs know to have their INR monitored within 3-5 days of starting Ensure they have access to patient information Patients on a new oral anticoagulant should know what to do if bleeding occurs and should carry an alert card 10