Anticoagulation Safe prescribing & Counselling

Anticoagulation Safe prescribing & Counselling

Xarelto (rivaroxaban) is subject to additional monitoring. Prescribing information is available at this meeting . Adverse events should be reported. Reporting forms and information can be found at: Adverse events should also be reported to Bayer plc. Tel.: 01635 563 500, Fax.: 01635 563 703 Email: [email protected] This meeting is organised and fully funded by Bayer Date of Prep: February 2016 L.GB.MKT.02.2016.14901 Medicines Optimisation in Anticoagulation Sharron Gordon Consultant Pharmacist Which of the following statements is incorrect? 1. Warfarin is licensed for the prevention of stroke in AF 2. DOACs are licensed for use in patients with mechanical valve replacements 3. Aspirin is no longer considered a suitable

option for prevention of AF related stroke 4. Frail elderly patients should not be anticoagulated Indications for anticoagulants Warfarin and all DOACs AF stroke prevention VTE treatment and secondary prevention VTE prophylaxis (may be extended in certain groups) Rivaroxaban only ACS Warfarin only Mechanical valves Moderate to severe mitral stenosis Other indications for anticoagulation (not AF / VTE) Heparins Bridging to warfarin VTE prophylaxis VTE treatment (cancer) Acute Coronary Syndrome Rationale for anticoagulation in AF AF most common sustained cardiac arrhythmia; 1-2% general population Prevalence increases with age (5-15% of 80 year olds)

Thromboembolic risk of AF is not homogeneous 1% patients aged 65 yrs with no risk factors 12% per year in patients with previous TE AF related ischaemic strokes are associated with increased morbidity and mortality risk of death doubled cost of care increased 1.5 fold AF is an increasingly important cause of stroke with increasing age % population attributable risk of stroke by age 60 Hypertension AF 53 49 45 33 % 30

24 15 10 3 0 60- 70- 80- Fitzmaurice & Murray: Oral Anticoagulation Management & Stroke Prevention. Hayward Medical Communications, 2002 Balancing. Benefits Warfarin is very effective in preventing stroke

Adjusted-dose warfarin compared with placebo or no treatment Warfarin better Placebo better AFASAK SPAF BAATAF CAFA SPINAF EAFT RRR 64%*, ARR 2.7% (95% CI: 4974%) All trials 100 50 0 RRR (%) Random effects model; Error bars = 95% CI; *p>0.2 for homogeneity; Relative risk reduction (RRR) for all strokes (ischaemic and haemorrhagic)

Hart RG et al. Ann Intern Med 2007;146:85767. 50 100 AFASAK = Atrial Fibrillation, Aspirin, Anticoagulation; SPAF = Stroke Prevention in Atrial Fibrillation; BAATAF = Boston Area Anticoagulation Trial for Atrial Fibrillation; CAFA = Canadian Atrial Fibrillation Anticoagulation; SPINAF = Stroke Prevention in Nonrheumatic Atrial Fibrillation; EAFT = European Atrial Fibrillation Trial Time in therapeutic range (TTR) impacts on survival time to stroke Warfarin group 1.0 71100% 6170% 5160% 4150% 3140% <30%

Non warfarin Cumulative survival 0.9 0.8 0.7 0.6 0 500 1000 1500 2000 Survival to stroke (days) Cox proportional hazards model for survival to post atrial-fibrillation stroke for patients at moderate or high risk of stroke CHADS2 2 by level of warfarin control Morgan CL et al. Thrombosis Research 2009;124:3741.

Narrow therapeutic range with VKA Target INR Ischaemic stroke (2.0-3.0) Intracranial haemorrhage Events / 1000 patient years 80 The anticoagulant effect of vitamin K antagonists are optimized when therapeutic doses are maintained within a very narrow range 60 40 20

0 <1.5 1.51.9 2.02.5 2.63.0 3.13.5 3.6-4.0 4.1-4.5 >4.5 Hylek EM, et al. N Eng J Med 2003; 349:1019-1026. I know I'm here to get my warfarin but can I have a DOAC? The DOACs vs Warfarin Warfarin

Dabigatran Pradaxa Rivaroxaban Xarelto Apixaban Eliquis Edoxaban Lixiana Company Generic Boehringer Ingelheim Bayer Bristol-Myers Squibb/ Pfizer

Daiichi-Sankyo Action II, VII, IX, X, Proteins C&S Direct thrombin inhibitor Factor Xa inhibitor Factor Xa inhibitor Factor Xa inhibitor Peak plasma level > 5 days 1.5 hrs

3 hrs 4 hrs 1-2 hours Half-life 1 week 14-17 hrs 9 hrs 12 hrs 6-11 hours Bioavailability 80-100% 7%

80% 50% 50% Elimination Metabolism Renal 80% Renal 33%, GI Renal 25%, GI Renal 35-39% Antidote Vitamin K & PCCs Idarucizumab

In progress In progress In progress Title Similar rates of ischaemic stroke with DOACs vs warfarin; dabigatran 150 mg bd associated with significantly lower rates Ischaemic stroke vs warfarin %/yr Warfarin %/yr HR (95% CI) Dabigatran 150 mg

0.86 1.14 0.75 (0.58-0.97) Dabigatran 110 mg 1.28 1.14 1.13 (0.89-1.42) Rivaroxaban 1.34 1.42 0.94 (0.75-1.17) Apixaban* 0.97

1.05 0.92 (0.74-1.13) *Ischaemic or uncertain type of stroke Favours DOACs 0.5 Hazard Ratio Clinical Trial Data for information only - no clinical conclusions should be drawn. Please refer to individual product SPCs for further information. 1. Connolly SJ et al. N Engl J Med 2009;361:113951; 2. Connolly SJ et al. N Engl J Med 2010;363:1875 1876; 3. Patel MR et al. NEJM 2011;365:88391 and Supplementary Appendix; 4. Granger et al. N Eng J Med 2011;365:981-92. Favours warfarin 1 1.5 Major bleeding a comparison with warfarin

Major bleeding vs warfarin %/yr Warfarin %/yr HR (95% CI) Dabigatran 150 mg 3.32 3.57 0.93 (0.81-1.07) Dabigatran 110 mg 2.87

3.57 0.80 (0.70-0.93) Rivaroxaban 3.6 3.4 1.04 (0.90-1.20 Apixaban 2.13 3.09 0.69 (0.60-0.80) Favours novel orals 0.5 Favours warfarin

1.5 1 Hazard Ratio Clinical Trial Data for information only - no clinical conclusions should be drawn. Please refer to individual product SPCs for further information. 1. Connolly SJ et al. N Engl J Med 2009;361:113951; 2. Connolly SJ et al. N Engl J Med 2010;363:1875 1876; 3. Patel MR et al. NEJM 2011;365:88391 and Supplementary Appendix; 4. Granger et al. N Eng J Med 2011;365:981-92. 14 DOACs are associated with a significantly lower incidence of ICH compared with warfarin Intracranial haemorrhage vs warfarin %/yr Dabigatran 150 mg %/yr

HR (95% CI) 0.32 0.76 0.41 (0.28-0.60) Dabigatran 110 mg 0.23 0.76 0.30 (0.19-0.45) Rivaroxaban 0.5 0.7 0.67 (0.47-0.93)

Apixaban 0.33 0.80 0.42 (0.30-0.58) Warfarin Favours novel orals 0 Favours warfarin 1 2.0 Hazard Ratio Clinical Trial Data for information only - no clinical conclusions should be drawn. Please refer to individual product SPCs for further information. 1. Connolly SJ et al. N Engl J Med 2009;361:113951; 2. Connolly SJ et al. N Engl J Med 2010;363:1875

1876; 3. Patel MR et al. NEJM 2011;365:88391 and Supplementary Appendix; 4. Granger et al. N Eng J Med 2011;365:981-92. 15 I am on warfarin .but I don't want that drug, can't I just have aspirin? Stroke risk reductions from randomized trials of antithrombotic agents in atrial fibrillation. Granger C B , Armaganijan L V Circulation 2012;125:159-164 Copyright American Heart Association Will I bleed? What are the other side effects Benefits v. risks of anticoagulation Treating 1000 patients with AF for 1 year with warfarin rather than aspirin would

Prevent 23 ischaemic Strokes Cause 9 additional major bleeds CHA2DS2VASc score Stroke no a/c Stroke c 1 6 2 2 25 8

3 37 12 4 55 17 5 84 27 a/ Is HAS-BLED any use? (sort of) HASBLED Major bleed Major bleed score no a/c a/c

1 3 7 2 7 19 3 9 24 4 13 34 Most bleeds

occur in 1st year of treatment Bleeders tend to bleed Annual stroke rate by subgroups ICH Ischaemic stroke 13.7 14 Traumatic ICH: 2.0 (fallers) vs 0.34% (other) 10. % 6.9 7

3.5 2.8 2.8 1.1 0.5 0 F Oth 1. Am. J. Med 2005; 118: 612-617 Tri Anticoagulants & Antiplatelets cross-talk Anticoagulants Warfarin Platelets Coagulation

cascade Collagen + other mediators Rivaroxaban Apixaban Edoxaban (Betrixaban) Factor Xa Thromboxane Dabigatran Thrombin Thrombin ADP Antiplatelets Aspirin

Clopidogrel Prasugrel Ticagrelor Activated platelet Fibrinogen GPIIb/IIIa Platelet aggregation Fibrin Clot GPIIb/IIIa inhibitors eg. Abciximab Tirofiban Person-centred care Source: Person-Centred Care made simple [The Health Foundation October 2014]

Increasing the effectiveness of adherence interventions may have a greater impact of the health of the (world) population than any improvement in medical treatment RB Haynes MD, MSc, PhD, Professor department of clinical epidemiology and biostatistics, McMaster University The issue of adherence According to NICE, between a third and a half of all medicines prescribed for long-term conditions are not taken as recommended 1 Poor adherence can severely compromise the effectiveness of treatment2 Poor adherence not only affects clinical outcomes, but also represents a waste of healthcare resources2 The estimated annual drug cost of unused or unwanted medicines in the NHS is around 100 million per year1 NICE = National Institute for Health and Clinical Excellence 1. Nunes V et al. (2009). Clinical Guidelines and Evidence Review for Medicines Adherence: involving patients in decisions about prescribed medicines and supporting adherence. London: National Collaborating Centre for Primary Care and Royal College of General Practitioners. 2. World Health Organisation. Adherence to long-term therapies: evidence for action (2003) Dabigatran levels & DCCV Comparison APTT vs Dabigatran Clotting Assay

40 patients pre DCCV 0.5 DTICtug/mL 0.4 0.3 0.1 R = 0.02 0 0 22.5 APTTs 45 APTT (mostly) ok for measuring effectiveness (TT=no clot) Significant numbers of patients had no detectable

anticoagulant on testing.. Needham et al. ISTH 2013 90 120% Portsmouth- Total exceptions by practice comparison 2013-14 2014-15 Underlying achievement net of exceptions (%) 80 Patients receiving intervention (%) 100% 70 Total Exceptions

60 80% 50 60% 40 30 40% 20 20% 10 0 0% 1 2 3

4 5 6 7 8 9 10 11 12 13 14 15 16

17 18 19 20 21 22 23 24 Badgerswood and Forest Surgery (interim data) 25% (n=5) have been newly started on anticoagulation. 15% (n=3) have been referred to HHFT for specialist review or initiation of anticoagulation 55% (n=11) were on warfarin and all have had full counselling plus written information to try to stabilise their INRs without the need to change the drug.

10% (n=2) have had antiplatelet agents stopped one patient prescribed dual therapy with dabigatran. Most importantly, patient satisfaction has been high with patients really grateful for the time that they got to talk about their medicines and rating the session at 4.94 overall (range 1, poor 5, excellent): All patients were sent for additional counselling at the community pharmacy. This session really helped me to better understand my medicines, thank you for spending time with me. All of this session was useful to helping me to better manage my warfarin. I have been measuring out vegetables on a daily basis to not exceed 8 portions a week. I really like vegetables so this makes me miserable. I have a mechanical heart valve and my INR fluctuates often. Understanding the vitamin k content of food has helped me to understand how my diet is effecting my INR. I thought when I was told that I was low risk (by the cardiologist) that it was about my risk of more palpitations. Nobody had mentioned a risk of stroke before. Ive been struggling with controlling my INR, it has really helped to talk about what I can do to try to manage it better. %of patients in AF who were anticoagulated prior to stroke SSNAP Register - Patients in AF admitted to hospital for stroke who had been prescribed anticoagulation prior to their stroke, by CCG

Quarterly data - Apr 2014 to Mar 2015 80% 70% 60% 50% 40% 30% 20% 10% 0% Apr-Jun 2014 Jul-Sep 2014 Oct-Dec 2014 Jan-Mar 2015 There are many reasons why people dont get the most out of medicines Barriers to optimal use of medicine Examples Professional

Practical Information Lifestyle choices Beliefs about medicine Inappropriate prescribing Mistakes in dispensing or administration Forgetfulness Inability to open containers n t o N ten In l a n io

Instructions not understood Poor understanding of condition/treatment Unpleasant side effects Inconvenience No perceived benefit Unnatural Addictive Poisonous Diminishing efficacy t n te n I l a n io NMS Who is Eligible:

Patients with Asthma & COPD. Type 2 Diabetes. Hypertension. Antiplatelets / Anticoagulants Targeted Medicines Use Review (MuR). Supports patients recently discharged. Helps improve transfer of care between settings. Managing Side Effects Dizziness & sickness, Bleeding in eyes, Heavy periods, Bleeding gums, Other bleeding,

Most days I feel fine so I just cut my tablet in half and just take half General Counselling Reduces the chance of unwanted blood clots forming which helps prevent strokes Take regularly , any time is ok when would be easiest for you? Warfarin evening to coincide with INR test Forgotten doses warfarin if before midnight dabigatran & apixaban if within 6 hrs of next dose (miss) rivaroxaban take immediately, do not double within the same day Like all medicines unwanted side effects If unusual bleeding, such as dark or bloody stools, urine or unexplained bruising tell your doctors NSAIDs cant be taken with anticoagulants Specifics dabigatran Indigestion Warfarin Counselling

When to take - Same time each day (evening) Alcohol - May potentiate warfarin moderation; no binges Risk of bleeding - A&E if nose/gums bleed blood in urine/stools Follow up - Regular clinic attendance Aspirin - Only if prescribed Reason for taking - AF, DVT, PE Interactions - Drugs inc OTC, green salad, cranberry Notify - GP, Dentist, Pharmacist INR - Range Skipped dose - Dont double up End of course Dose - 1mg brown 3mg blue 5mg pink Patient information

Patient information for warfarin / DOACs s/a-z-departments-and-specialities/h/haemophilia, -haemostasis-and-thrombosis-centre.aspx NICE patient decision aid cg180-atrial-fibrillation-update-patient-decision-aid 2 ANTICOAGULANT & THROMBOSIS CENTRE CONTACT DETAILS Anticoagulant Practitioners Hours: MonFri 9.30 16.30 GP Direct Phone number 01256 313415 / 07876 508503 Patient Phone number 01256 313295 / 01962 825624 Fax Number 01256 314889 / 01962 825941 Bleep 1499 Bas / 093 Winch Email [email protected] (email can be used for referrals and enquiries) Consultant Haematologist 01256 314793 working day 07867141059 (on call only after 5pm) [email protected] (emails answered within one working day)

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