DOAC Educational Webinar 12 th November 2020 1-2pm and repeated 17 - - PowerPoint PPT Presentation

DOAC Educational Webinar

 12th November 2020 1-2pm and repeated 17th November 2020 7-8pm  Thank you to everyone involved in caring for patients taking

anticoagulation in South East London

 The aim of this session is to ensure that:

• You are aware of the changes to the transfer of care for patients prescribed DOACs

(in place from 1st October 2020)

• You have the support and guidance to monitor patients taking DOACs to ensure their

safety and effectiveness

• You know when to seek advice and guidance from hospital teams or medicines
• ptimisation teams
• You are able to prescribe DOACs in elderly and frail patients and according to their

risk:benefit

DOAC Educational Webinar: Housekeeping

 This webinar is being recorded, we ask you all mute yourselves. The

recording will be uploaded and you will receive a link to this webinar.

 There will be opportunities for you all to ask questions, you can do this by

using the chat function on Microsoft Teams.

 Please use the raise your hand function on Microsoft Teams to indicate

your answer to any questions asked.

Agenda

 Welcome, introductions and overview: Helen Williams (SEL CCG)  DOAC pathways and support for primary care: Rachel Howatson (SLCVMWG)  Case study 1: A low risk patient: Rosalind Byrne (12th) or Georgina Harrison (17th) (LGT)  Case study 2: A high risk patient: Rosalind Byrne (12th) or Alison Brown (17th) (KCH)  Monitoring of DOACs in primary care: Helen Williams (12th) or Vicki Collings (17th)

(GSTT)

 DOACs in the elderly +/- frail: Dr Raj Patel (haematologist- KCH)  Q & A  Useful references

SEL DOAC patient pathways: Why do we need to change?

Identified Issue Learning Points Communication issues TOC and initiation forms not received by primary care or incorrectly coded on EMIS Differences in practice Among specialities in acute Trusts and borough community clinics Waiting times for AC clinic Need to prioritise and risk:stratify patients referred Medicines compliance aids Safety issues with over/under coagulation- duplication of therapy and missed doses Unfamiliar prescribing DOAC choices and dosing regimes Annual reviews Are not being achieved New Medicines Service Promote community pharmacy support for DOAC adherence and counselling

SEL DOAC patient pathway for NVAF

SEL Actions Taken

Action Taken Outcomes

Preferred DOAC agents

Edoxaban for NVAF Rivaroxaban for VTE

Removal of TOC and initiation forms

Replace information in discharge and clinic letters Baseline blood tests, monitoring recommendations

TOC for NVAF at 1 month

Primary care to prescribe, review and monitor DOACs for NVAF following initiation- consistent with other medications supplied at discharge from hospital Supported by guidance and AC teams contactable by email

Define high risk patients in NVAF pathway

“High risk” patients followed up by AC clinics Consistency of referral among specialities and across interfaces

Medicines compliance aid and housebound patients

Encourage communication: Current variations in practise across SEL- primary care prescribing often required earlier

Primary care support tools

(see link SEL APC CV guidelines)

 FAQs for DOACs in primary care  Initiation of AC for NVAF (edoxaban)  AC choice for VTE (rivaroxaban)  Initiation and monitoring of DOACs template- includes dosing tables and

counselling checklist

 Calculating renal function for DOACs updated  DOAC patient pathway for NVAF  DOAC patient pathway for VTE  Table summary of changes from 1st October (SEL comms letter)  Stepwise approach to DOAC prescribing in primary care (summary page)  Educational webinars  Task and Finish group focusing on standards of AC community service

Case Study 1: Low risk DOAC patient

 Mr NL, 55 years  On warfarin for NVAF for the last 10 years (started in Vietnam,

recently moved to the UK)

 PMH: HTN, IHD (angina – no previous ischaemic event)  Medications: warfarin, amlodipine, ISMN, GTN spray  Social History: owner of a restaurant, drinks alcohol 1 pint of 4%

lager every night (16 units a week)

 CHADsVASC: 2 (HTN, IHD- angiographically significant CAD)- risk

factors for ischaemic stroke in AF patients

 HASBLED: 1 (ETOH) (maximum recommended 8 units a week)

First appointment in anticoagulation clinic: Secondary care

Struggling to make warfarin clinic appointments Time in Therapeutic Range = 38% (Target 65%) At AC clinic: discussed DOAC options (risks and benefits) Counselled: have 2 alcohol free days (aim <8 units a week) Adherence to medication supported Mr NL decided to switch to a DOAC

 See warfarin to DOAC guidance during COVID-19:  https://www.anticoagulationuk.org/downloads/NHS%20clinical%20guide

%20for%20management%20of%20anticoagulation.pdf

DOAC commenced

 Baseline Bloods Checked and in range on initiation: FBC, Renal

Profile, LFTs, INR 2.0

• See SEL initiation and monitoring template for DOACs

 Renal function (CrCl): Weight: 88.7kg, Cr 81, CrCl 114 ml/min

based on actual body weight

• See SEL renal monitoring guidance for DOACs

 Edoxaban not the best choice as CrCl >90mL/min hence cautioned

• See SEL Initiation of AC for NVAF guidance

 Rivaroxaban 20mg Once a day commenced the following day as

INR <3

DOAC initiation for NVAF- Special Circumstances

See SEL AC initiation for NVAF guidance

Special circumstances Recommendation Special circumstances Recommendation Special circumstances Recommendation Pregnancy/ Breast feeding LMWH preferred/ specialist advice Mechanical heart valves (includes TAVI/TAMI, tMVR or MV repair within 3 months) Warfarin/specialist advice- haematology/cardi

• logy

Severe renal impairment (CrCl < 15ml/min) Warfarin/specialist advice Active malignancy/ chemotherapy Specialist advice Moderate to severe mitral stenosis Warfarin High CrCl >95ml/min Rivaroxaban/specialist advice HIV antiretrovirals and hepatitis antivirals Specialist advice Post coronary event/intervention Cardiology advice: antiplatelet review Antiphospholipid Syndrome (APLS) Warfarin/specialist advice Menorrhagia Specialist advice Extremes of body weight <50kg and >120kg Specialist advice On anti-epileptic medication Specialist advice

Example clinic letter for this patient

 DOAC choice, indication and dose:

• Rivaroxaban 20mg Once a day started for NVAF and warfarin stopped

 Baseline Bloods:

• from 01/11/2020:- Hb: 156, ALT: 14, Weight: 88.7kg, Cr 81, CrCl 114

ml/min based on actual body weight

 DOAC supply given to patient:

• 4 weeks supply given on initiation

 Monitoring advice:

• GP please continuing prescribing and monitoring rivaroxaban
• Based on the initial bloods, recheck in one year (FBC, LFTs, renal

profile)

Follow up in Primary care

 This patient does not require secondary care follow up – See high risk criteria for AC clinic referral in DOAC patient pathway for NVAF  At next routine GP appointment:

• Check for side effects/bleeding issues
• Check adherence/understanding concerning therapy with patient
• Ensure supply of rivaroxaban is continued
• Next routine bloods required in one year based on initial bloods
• Review annually as may require more frequent monitoring in the future

(More on monitoring later)

• See SEL renal monitoring for DOAC guidance
• See SEL initiation and monitoring of DOACs template

Follow-up review – low risk patients

Weight Record weight (at least annually) Renal function Record CrCl (see SEL guidance for frequency- 3 to 6 to 12 monthly) Drug interactions including OTC Ensure repeat prescription is current Confirm other changes: if antiplatelet or NSAIDs deprescribed? PPIs started? Medicines adherence Check for non-adherence and address as appropriate Bleeding or other adverse effects Review bleeding symptoms and adverse effects Confirm understands red flags for bleeding If not tolerated, refer back to anticoag clinic/clinician who initiated Thromboembolism Confirm patient is clear on indication and duration Re-educate as appropriate Modifiable factors for bleeding e.g. concurrent medications, uncontrolled BP and EtOH intake Monitoring plan Document appropriate plan (see later slide)

The 2018 European Heart Rhythm Association Practical Guide on the Use of Non-vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation; European Heart Journal (2018); 39 (16): 1330-1393. Accessible via: https://doi.org/10.1093/eurheartj/ehy136. SEL Integrated Medicines Optimisation Committee: Direct Oral Anticoagulant (DOAC) Initiation and Monitoring Guidance Template. September 2020. Available via: https://www.lambethccg.nhs.uk/news-and-publications/meeting- papers/south-east-london-area-prescribing-committee/Documents/Cardiovascular%20Disease%20Guidelines/DOAC%20initiation%20and%20monitoring%20template%20SEL%20SEPT%202020%20FINAL.pdf

High risk patient will be followed up by anticoagulation clinics

Case Study 2: High risk patient

 Mrs TP, 76 years old, new diagnosis of NVAF  PMHx: HTN, DM, CABG 2015, Hyperlipidaemia  DHx: ramipril, metformin, frusemide, simvastatin, bisoprolol, aspirin  Social: No alcohol, lives with partner  CHA2DS2-VASc score 6 , HAS-BLED score 1- modifiable risk factor is current

antiplatelet therapy

 Weight 135kg, Height 163cm  Referred from cardiology to start anticoagulation for stroke prevention

First appointment in anticoagulation clinic

• secondary care

 Not keen on regular INR testing  Option of a DOAC discussed (risks and benefits), prefers once a

day dosing

 Baseline tests: AST 25 IU/L, Hb 134 g/L  Cr 86 µmol/L  Actual bodyweight >120kg, use adjusted body weight for CrCl

calculation:

• Weight 135kg, Height 163cm
• Ideal body weight (IBW) 55kg, Adjusted Body Weight (ABW) = 87kg

Renal function: CrCl = 68ml/min based on ABW 87kg

• Use MDCALC: https://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation
• See SEL calculating renal function for DOACs guidance

www.mdcalc.com for renal function (CrCl) calculations

Actual weight IBW ABW Adjusted body weight (ABW) Use actual weight if <120kg For patients >120kg need: Gender Age Weight Cr AND Height

ISTH 2016 – DOACs in obesity

• 1. We suggest DOACs should not be used in patients with a BMI of > 40 kg m−2
• r a weight of > 120 kg, due to concerns about under dosing in the population

at the extremes of weight.

• 2. If DOACs are used in a patient with a BMI of > 40 kg m−2 or a weight of > 120

kg, we suggest checking a drug‐specific peak and trough level.

• 3. If the level falls within the expected range, continuation of the DOAC seems

reasonable.

• 4. However, if the drug‐specific level is found to be below the expected range we

suggest changing to a VKA rather than adjusting the dose of the DOAC.

 No recommendation on low body weight

DOAC commenced by AC clinic

Data on adequate exposure and emerging efficacy data

with rivaroxaban in high body weight patients

Initiated on rivaroxaban 20mg once daily WITH FOOD Mrs TP was counselled, given written information and a

yellow alert card

• See counselling checklist in SEL DOAC initiation and

monitoring template

Aspirin stopped as CABG 2015, no further issues

Follow up in Secondary care

 Patient meets criteria for follow up in secondary care : > 120kg  Follow up review 2 weeks later:

• Tolerating rivaroxaban well
• Taking with breakfast
• No dizziness/headaches, no bruising/bleeding
• Counselling repeated to encourage adherence to DOAC therapy

 Trough level 83 ng/ml – in range, adequate  For discharge from clinic and transfer to GP

Example clinic letter for this patient

Clinic letter documents:

 DOAC choice and indication: Rivaroxaban 20mg once a day with food started for

stroke prevention in NVAF

 Baseline bloods including date taken: Cr 86 µmol/L, AST 25 IU/L, Hb 134 g/L  Renal function: Weight 135kg, height 163cm, CrCl 67ml/min based on ABW 87kg  Information given to patient: Counselled and given PIL and alert card  DOAC supply: 4 weeks supply given on initiation  TOC: GP please continuing prescribing and monitoring rivaroxaban  Monitoring requirements: Based on patient age over 75 years: recheck in 6

months (FBC, LFTs, renal profile)

• The 2018 European Heart Rhythm Association Practical Guide on the Use of Non-vitamin K

Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation; European Heart Journal (2018); 39 (16): 1330-1393. Accessible via: https://doi.org/10.1093/eurheartj/ehy136

Follow up in Primary care

 At next routine GP appointment:

• Check for side effects/bleeding issues
• Check patient adherence/ understanding around anticoagulation therapy
• Reinforce importance of taking rivaroxaban with food
• Ensure supply of rivaroxaban is continued

 Next routine review required in six months based on initial bloods and patient age:

– See SEL Initiation and Monitoring of DOACs template

• Blood tests: FBC, LFTs, Renal Profile
• Check up to date weight to calculate CrCl (ABW if still >120kg)
• Review renal function as may require more frequent monitoring in the future

– See SEL guidance Calculating renal function for DOACs

• Check dose is still appropriate
• Advice/treatment of modifiable HASBLED factors

Monitoring of DOACs in primary care

Vicki Collings Consultant Pharmacist- Haemostasis and Thrombosis Guy’s and St Thomas’ NHS Foundation Trust Helen Williams Consultant Pharmacist for CVD SE London CCG

Annual r rev eview ew – for all patients

Age Check if DOAC dose adjustment needed for apixaban Weight Check if DOAC dose adjustment needed for edoxaban/apixaban Full blood count New anaemia or thrombocytopenia: investigate as appropriate Liver function New liver dysfunction: bilirubin >1.5 ULN or AST/ALT > 2 ULN, refer for advice Renal function Calculate CrCl Drug interactions including OTC Check for any interacting drugs that may require monitoring, dose adjustment or de-prescribing Medicines adherence Explore any reasons for non-adherence and strategies to help Opportunity to re-educate patient on indication Bleeding or other adverse effects Review bleeding symptoms, preventative measures and explain red flags Consider if temporary cessation or an alternative is needed Thromboembolism Signs and symptoms of VTE/Stroke Modifiable factors for bleeding e.g. concurrent medications, uncontrolled BP and EtOH intake Check dose Review above and confirm current dose is appropriate Review monitoring plan See later slide

The 2018 European Heart Rhythm Association Practical Guide on the Use of Non-vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation; European Heart Journal (2018); 39 (16): 1330-1393. Accessible via: https://doi.org/10.1093/eurheartj/ehy136. SEL Integrated Medicines Optimisation Committee: Direct Oral Anticoagulant (DOAC) Initiation and Monitoring Guidance Template. September 2020. Available via: https://www.lambethccg.nhs.uk/news-and-publications/meeting- papers/south-east-london-area-prescribing-committee/Documents/Cardiovascular%20Disease%20Guidelines/DOAC%20initiation%20and%20monitoring%20template%20SEL%20SEPT%202020%20FINAL.pdf

DOACs – Calculating Creatinine Clearance

1. https://bmjopen.bmj.com/content/3/9/e003343 2. Calculating Renal Function (Creatinine Clearance) When Monitoring Direct Oral Anticoagulants (DOACs) For Safe and Effective Dosing Of Patients. Available at: http://www.lambethccg.nhs.uk/news-and-publications/meeting-papers/south-east-london-area-prescribing- committee/Documents/Cardiovascular%20Disease%20Guidelines/Calculating%20renal%20function%20for%20DOACs%20Sept%202019%20FINAL.pdf

eGFR should not be used to guide dosing decisions for DOACs1 Use up to date (within 1 year) actual bodyweight to calculate Creatine Clearance (CrCl)

• If weight < 50kg or > 120kg (adjusted BW for over 120kg) or if BMI >40 : seek specialist advice if bleeding concerns or antiXa

level required Use renal function checked within last 3 months Calculate CrCl using Cockcroft Gault equation

• Be cautious with calculators integrated into GP IT systems as they may default to

ideal bodyweight resulting in underdosing of DOAC ;

• Use MDCalc

Adjust DOAC dose if necessary See slide on DOAC dosing in NVAF

If Cr CrCl Cl… Repeat Cr CrCl Cl… >60ml/min Annually 30-60ml/min 6-monthly <30ml/min 3-monthly

Moni

• nitoring pl

g plan

• Review the monitoring plan for the year:
• Having variable monitoring plans in GP practices can be challenging to

manage

• Consider using “review date” function on EMIS, adding blood test

date to prescription and/or regular reporting of over-due bloods

Creatinine Clearance (CrCl) Frequency of U&E Monitoring Frequency of FBC and LFTs Monitoring >60 ml/min Every 12 months Every 12 months 30-60 ml/min Every 6 months Every 12 months 15-30 ml/min At least every 3 months Every 12 months (see frail below) < 15ml/min Refer to anticoagulation (all DOACs CI) Aged ≥ 75yrs or frail Every 6 months Every 6 months

The 2018 European Heart Rhythm Association Practical Guide on the Use of Non-vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation; European Heart Journal (2018); 39 (16): 1330-1393. Accessible via: https://doi.org/10.1093/eurheartj/ehy136. SEL Integrated Medicines Optimisation Committee: Direct Oral Anticoagulant (DOAC) Initiation and Monitoring Guidance Template. September 2020. Available via: https://www.lambethccg.nhs.uk/news-and-publications/meeting- papers/south-east-london-area-prescribing-committee/Documents/Cardiovascular%20Disease%20Guidelines/DOAC%20initiation%20and%20monitoring%20template%20SEL%20SEPT%202020%20FINAL.pdf

Dabigatran1 Apixaban2 Edoxaban3 Rivaroxaban4 Standard dose 150mg BD 5mg BD 60mg OD 20mg OD Reduced dose 110mg BD 2.5mg BD 30mg OD 15mg OD Criteria for dose reduction

• 1. Age≥80
• 2. On verapamil
• 3. Consider ↓dose:
• Reflux/gastritis
• Age75-80
• CrCl 30-50ml/min
• “Bleed risk”

2 or more of:

• Age ≥80
• Body weight ≤60kg
• Cr ≥133μmol/L

Or CrCl 15-29ml/min 1 or more of:

• CrCl 15-50ml/min
• Body weight ≤60kg
• On ciclosporin,

dronedarone, erythromycin, ketoconazole CrCl 15-49ml/min Contraindicated / Not recommended CrCl <30ml/min CrCl <15ml/min CrCl <15ml/min CrCl <15ml/min

1. Dabigatran SmPC. Available at www.medicines.org.uk; 2. Apixaban SmPC. Available at www.medicines.org.uk; 3. Edoxaban SmPC. Available at www.medicines.org.uk; 4. Rivaroxaban SmPC. Available at www.medicines.org.uk.

DOAC Dosing in Non Valvular Atrial Fibrillation

Reviewing Drug Interactions Bleeding risk affected by

Antifungal agents Antidepressants: SSRIs/SNRIs Rifampicin NSAIDs Phenytoin and anti-epileptics Antiplatelets Antiretrovirals Chemotherapy Antiplatelet courses and durations should be reviewed: Seek advice and guidance from cardiology/vascular/stroke “Triple therapy” should be followed up by AC clinic

See SEL DOAC initiation and monitoring guidance

AB ABCD f for

• r dos

dosing of

• f

DO DOACs Cs

• Age
• Body weight
• Creatinine

clearance

• Drug interactions

This Photo by Unknown Author is licensed under CC BY-SA

What i infor

• rmation d
• n do I need t

ed to give t e to the p e patien ent?

• See counselling checklist in SEL DOAC

initiation and monitoring guidance

• For anticoagulation cards (OAT alert):
• Supplier for GP Practices now Primary care Support

England (not Xerox via nhs.forms.co.uk)

• Email: pcse.supplies-leeds@nhs.net OR

PCSE.DataManager@nhs.net OR PCSE.AdHoc- MR@nhs.net

SEL Integrated Medicines Optimisation Committee: Direct Oral Anticoagulant (DOAC) Initiation and Monitoring Guidance Template. September 2020. Available via: https://www.lambethccg.nhs.uk/news-and-publications/meeting- papers/south-east-london-area-prescribing-committee/Documents/Cardiovascular%20Disease%20Guidelines/DOAC%20initiation%20and%20monitoring%20template%20SEL%20SEPT%202020%20FINAL.pdf

Whe hen to r

• refer

er to A

• AC c

C clinic for

• r advi

dvice? ce?

• Dosing/duration queries for AF and VTE patients
• CrCl ≤ 15ml/min
• Liver dysfunction: bilirubin >1.5 ULN or AST/ALT > 2 ULN
• AntiXa monitoring, not documented at initiation:
• Extremes of weight <50kg or >120kg
• Pharmacokinetic drug interactions
• Absorption concerns e.g GI surgery or gastric bands
• Edoxaban and CrCl >95ml/min
• Bleeding issues or other adverse effects
• New cancer diagnosis
• Advice about switching between DOACs/VKAs
• To support anticoagulation for housebound or nursing home patients
• See Direct Oral Anticoagulant (DOAC) Referral Pathway for Non-Valvular Atrial

Fibrillation (NVAF) Patients In South East London (Secondary to Primary Care)

SEL Area Prescribing Committee: Direct Oral Anticoagulant (DOAC) Referral Pathway for Non-Valvular Atrial Fibrillation (NVAF) Patients In South East London (Secondary to Primary Care) March 2020. Available via: https://www.lambethccg.nhs.uk/news-and-publications/meeting-papers/south-east-london-area-prescribing- committee/Documents/Cardiovascular%20Disease%20Guidelines/DOAC%20patient%20referral%20pathway%20NVAF%20March%202020.pdf

Anticoagulation in Practice: The High - Risk Patient

Dr Raj Patel

King’s Thrombosis Centre King’s College Hospital

No head-to-head clinical trial comparisons between apixaban, rivaroxaban and dabigatran have been

• performed. This data should therefore be interpreted with caution.

* * Ximelagatran withdrawn from market due to evidence of hepatotoxicity

Presented by AJ Camm at the Global Thrombosis Forum 2013, Prague.

Is major disabling stroke equal to (treatable) GI bleed?

Different perspectives

Patients fear strokes Physicians fear GI

CHA2DS2-VASc score Number of events per 1,000 AF patients per year HAS-BLED score AF related strokes prevented by anticoagulation Major bleeds caused by anticoagulation 1 4 4 1 2 17 12 2 3 25 15 3 4 38 21 4 5 57

The risk of AF-related stroke depending on CHA2DS2-VASc score and the effects of anticoagulants on that risk1

This table is based on the likely risk/benefit of warfarin in AF patients. The NOACs have been shown to be at least non-inferior to warfarin in terms of reducing ischaemic stroke in AF patients. Dabigatran 150 mg has actually been shown to be superior to warfarin in reducing ischaemic stroke.2 The NOACs have been shown to be not significantly more hazardous than warfarin in terms of causing major bleeds in AF patients. Dabigatran 110 mg and apixaban 5 mg have actually been shown to be associated with significantly fewer major bleeds than warfarin.2,3

• 1. Adapted from NICE. Patient Decision Aid – Atrial fibrillation: medicines to help reduce your risk of a stroke – what are the options.

Available at: https://www.nice.org.uk/guidance/cg180/resources/patient-decision-%20aid-243734797. Accessed March 2018;

• 2. Dabigatran SmPC; 3. Apixaban SmPC.

Unmet Need

In the patients with known AF, not anticoagulated at the time of stroke

 26% patients died  45% left with moderate to severe disability

‘High risk’?

My patient is too old

My patient has falls My patient is too frail

My patient will bleed

My patient has poor renal function

The Challenges of Anticoagulation in AF

 Prevalence of AF increases with age  Age alone is an important risk factor for stroke1,2

• 55+ years: After the age of 55 years, stroke risk doubles for each 10 years of life3

 Warfarin reduces stroke risk by ~60% versus antiplatelet therapy or placebo (N=28,044)4  Major bleeding risk is higher in elderly compared with younger patients taking warfarin (N=472)5

4.1 9 18 28.7 55 42.5 97.9 142.9

40 80 120 160 50−59 60−69 70−79 80−89

No AF AF

Stroke1

2-year incidence (per 1000 patients) Age group (years)

AF, atrial fibrillation

• 1. Wolf PA et al, Arch Intern Med 1987;147:1561–1564; 2. Marinigh R et al, J Am Coll Cardiol 2010;56:827–837; 3. Sacco RL et al, Stroke 1997;28:1507–1517; 4.

Hart RG et al, Ann Intern Med 2007;146:857–867.

Older AF patients less likely to get warfarin

Gallagher AM et al. J Thromb & Haem 2008;6:1500-1506

Younger Older

Balancing benefits vs. risks Are all bleeds equal?

• Hb drop of ≥ 2g/dl
• Transfusion of ≥ 2 U
• Symptomatic bleeding in critical organ
• Fatal haemorrhage: 0.4%
• Intracranial haemorrhage 0.8%

Major bleeding 5%

Fatal Bleeding 0.4 %

All bleeding events: 20%

The risk of ischaemic stroke "without" OAC exceeds the risk of intracranial bleeding "with" OAC*

Relation between risk scores and annual event rates

• f ischaemic stroke and ICH in relation to use of oral anticoagulation

in 159,013 Swedish AF patients followed up for 1.5±1.1 yrs (2005–2008)

CHA2DS2-VASc score Annual event rate Score

1 2 3 4 5 6 7 8+

Stroke [no OAC] Stroke [OAC] ICH [OAC] ICH [no OAC]

0% 2% 4% 6% 8% 10% 12% 14% 16% 18%

HAS-BLED score Annual event rate

0% 2% 4% 6% 8% 10% 12% 14% 16% 18%

Score

1 2 3 4 5+

Stroke [no OAC] Stroke [OAC] ICH [OAC] ICH [no OAC]

*Except those with a very low risk of stroke

Adapted from Friberg et al. Circulation 2012;125:2298–307.

Reducing risk of bleeding

• 1. Control BP
• 2. Review benefit/ risk of concomitant aspirin:

 Hypertensives, diabetics, CHD and no acute ischemic event or intervention in the last year

 Stop aspirin when INR in therapeutic range

• 3. Risk of bleeding is greatest in first 90 days of OAC therapy

 Caution : drug interactions and new drugs  Close or more frequent monitoring

• 4. Review concomitant use of NSAIDS, SSRIs, steroids
• 5. Consider a PPI, for selective high risk patients

Hylek, E.M., Evans-Molina, C, Shea, C. et al. (2007), Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation, Circulation, 115, 2689-2696.

Patients with AF and renal impairment

• Every third patient with

AF has chronic kidney disease (CKD)1

• Prevalence of both AF

and CKD increase with age1

• 1. Hart RG et al, Can J Cardiol 2013;23:S71–S78

Stage IV eGFR 15-29 mL/min

2%

Stage V eGFR < 15 mL/min

1%

Stage I and II eGFR > 60 mL/min Stage III eGFR 30-59 mL/min

30% 67% Frequency of CKD in AF patients1

Patients with AF and renal impairment

• Patients with AF and

renal impairment

– Are at higher risk of bleeding

and stroke than those with normal renal function1

– Are more often undertreated

with warfarin than those with normal renal function2

3.61 3.54 6.44 8.77 2 4 6 8 10 Stroke or thromboembolism Bleeding Event rate/100 person-years

HR 1.49 (95% CI 1.38-1.59)

Danish registry1 (N=132,372) (~28% of patients received warfarin)

• 1. Olesen JB et al, N Engl J Med 2012;367:625–635; 2. Capodanno D et al, Circulation 2012;125:2649–2661

Without renal disease (n=127,884) Non-end-stage CKD (n=3587)

HR 2.24 (95% CI 2.10-2.38) P<0.001

NOACs (vs Warfarin)

Ischemic Stroke Or Bleeding: Patients With AF And CKD

OR (95% CI) p-value

Mild renal impairment (CrCl [eGFR] 50–79 ml/min) Major/CRNMB bleeding 0.80 (0.71–0.90) 0.0002 Stroke/SE 0.70 (0.54–0.92) 0.010 Moderate renal impairment (CrCl [eGFR] 30–49 ml/min) Major/CRNMB bleeding 0.81 (0.54–1.21) 0.29 Stroke/SE 0.72 (0.57–0.92) 0.008

Safety And Efficacy Of NOACs vs VKA In Patients With Renal Impairment

Sardar et al. Can J Cardiol 2014;30:888–97.

0.5 1 2

Favours NOAC Favours VKA

Edoxaban: Outcomes in patients at increased risk of falls

ICH=intracranial haemorrhage; SSE=stroke or systemic embolism

Efficacy and safety of edoxaban vs warfarin in patients with and without risk of falls at baseline

There was no significant interaction by treatment group in patients with vs without an increased risk of falling (all P > 0.05). Patients at risk of falls were at a significant risk of ICH, which was reduced with edoxaban

12 10 8 6 4 2 Event rates/100 patient years Stroke/SEE All cause death/stroke/S SE All-cause death Major bleed 2.8 Warfarin at risk Edoxaban at risk ICH Bone fracture due to fall 9.1 2.8 1.5 1.8 9.3 10.0 4.8 5.4 7.1 7.8 3.9 4.2 5.4 5.6 2.8 3.5 0.3 2.1 0.4 0.8 4.4 4.5 1.5 1.7 Warfarin not at risk Edoxaban not at risk

Steffel J et al. Presented at AHA 2015. Steffel J et al; 2016

Dose adjustments in AF1-4

• 1. Rivaroxaban SmPC; 2. Apixaban SmPC; 3 Dabigatran SmPC; 4. Edoxaban SmPC.

Not recommended Estimate CrCl 15 mg OD 20 mg OD 30–50 mL/min

≥80 years

• r taking

verapamil 75–80 years;

• r with gastritis,

esophagitis or gastroesophageal reflux; or increased bleeding risk See Footnote Contraindicated

110 mg BID 150 mg BID 110 mg BID

2.5 mg BID 5 mg BID

Rivaroxaban1 Apixaban2 Dabigatran3 Edoxaban4

>50 mL/min Estimate CrCl <15 mL/min

≥80 years If ≥2 features If ≤1 features

Not recommended

Estimate CrCl <15 mL/min

Not recommended

≥80 years

• r taking

verapamil

Estimate CrCl

75–80 years;

• r with gastritis,

esophagitis or gastroesophageal reflux; or increased bleeding risk See Footnote

110 mg BID

15–29 mL/min 2.5 mg BID

110 mg BID 150 mg BID 110 mg BID 150 mg BID

See Footnote

<30 mL/min

Footnote: 110 mg or 150 mg BID based on individual assessment of thromboembolic & bleeding risk Check age ≤60 kg Check weight

Check serum creatinine

≥133 µmol/l

15–49 mL/min ≥50 mL/min 60 mg OD ≤60 kg

Potent P-gp Inhibitors*

30 mg OD 30 mg OD 30 mg OD

*CrCl 15-29 mL/min – to be used with caution *ciclosporin, dronedarone, erythromycin, ketoconazole

<15 mL/min 15–49 mL/min* ≥50 mL/min ≥30 mL/min

Dr R Raj P j Pate tel

King’s Thrombosis Centre King’s College Hospital

rajpatel@nhs.net www.kingsthrombosiscentre.org.uk

DOAC dosing comparison for NVAF (taken from SEL DOAC initiation/monitoring guidance):

SPC hyperlinks: Edoxaban Rivaroxaban Apixaban Dabigatran

Standard dose 60mg OD 20mg OD (with food) 5mg BD 150mg BD Reduced dose 30mg OD 15mg OD (with food) 2.5mg BD 110mg BD Criteria for reduced dose ≥ 1 of

• weight ≤ 60kg
• CrCl 15-50ml/min
• On ciclosporin,

dronedarone, erythromycin, or ketoconazole CrCl 15- 49ml/min ≥ 2 of;

• Age ≥ 80yrs
• weight ≤ 60kg
• Cr ≥ 133µmol/L

OR CrCl 15-29ml/min

• Age ≥ 80 yrs
• On verapamil
• Consider for: Reflux/gastritis, Age

75-80 yrs, CrCl 30 -50ml/min, or “Bleed risk” Contra-indicated CrCl <15ml/min (caution CrCl >95ml/min) CrCl <15ml/min CrCl <15ml/min CrCl <30ml/min

Questions and Answers?

Useful References

 SEL APC CV guidance: https://www.lambethccg.nhs.uk/news-and-publications/meeting-papers/south-east-london-area-prescribing- committee/Pages/default.aspx?RootFolder=%2Fnews%2Dand%2Dpublications%2Fmeeting%2Dpapers%2Fsou th%2Deast%2Dlondon%2Darea%2Dprescribing%2Dcommittee%2FDocuments%2FCardiovascular%20Disease% 20Guidelines&FolderCTID=0x0120008DD723BCD38271408DD3087856A790D0&View=%7BFAC29531%2DFE95 %2D4CA2%2DB44C%2DCF0BFCC5095F%7D



Guidance on switching from warfarin to DOAC during COVID-19: https://www.anticoagulationuk.org/downloads/NHS%20clinical%20guide%20for%20management%20of%20 anticoagulation.pdf



See also GP notebook shortcut- direct oral anticoagulant dosing for stroke prevention in NVAF (subscription required): https://www.gpnotebookeducation.com/pdf/GPnSHORTCUTS_DOAC_V3.pdf



For drug interactions see: British National Formulary link: https://bnf.nice.org.uk/interaction/ and Summary

• f Product Characteristics (SPC) https://www.medicines.org.uk/emc for each DOAC and for antiretroviral

medicines see: https://www.hiv-druginteractions.org/



Please also contact your local borough medicines optimisation teams for any support or advice in the usual manner