Atrial Fibrillation in the Rural Community – is it any different?

Dr Allison Morton

Heartcare WA

SJOG Bunbury

People? Spot the difference…

What about the location?

Equipment?

Hazards?

So… are there differences?

• People – No

• Location – Yes

• Equipment – Yes

• Hazards - Yes

Atrial Fibrillation

• What is AF and why does it happen

• Where are we at preventing AF

• How hard do we /should we look for AF • Does asymptomatic AF matter

• Balancing stroke risk and bleeding risk

• Rate v Rhythm how to decide

• What else is out there?

8

Ball et al. MJA 202 (1) · 19 January 2015

By 2034, AF prevelance expected to be over 600,000 patients

• 1 in 4 adults over age 40 develop AF in their lifetime

• Incidence increases with age: 2 to 3 cases per 1000/yr at age 55-64 y, and upto 35 cases per 1000/yr between age of 85-94

• AF is more common in whites than in black and Indo-Asian people

• First-ever ischemic stroke: prevalence of AF 15-25%, and incidence 5%

• New-onset AF 10% (AMI) and 20%(HF)

• Genetic pre-disposition

Epidemiology

Extracardiac

Factors:

Hypertension

Obesity

Sleep apnea

Hyperthyroidism

Alcohol/drugs

Atrial Structural

Abnormalities:

Fibrosis

Dilation

Ischemia

Infiltration

Hypertrophy

Inflammation

Oxidative stress

Atrial tachycardia

remodeling

Genetic Variants:

Channelopathy

Cardiomyopathy

RAAS activation

Autonomic

nervous system

activation

Atrial Electrical

Abnormalities:

↑Heterogeneity

↓Conduction

↓Action potential duration/refractoriness

↑Automaticity

Abnormal intracellular Ca++

handling

AFP

ath

op

hys

iolo

gy

What makes someone have AF?

Triggers

Substrate

Age, hypertension, OSA,alcohol, IHD,weight etc

alcohol, infection, ischaemia, post surgery, thyrotoxicosis

Diagnosis?

• Is this a clinical diagnosis?

• What do you need to be diagnosed with AF?

Detection of AF

• Get people into the habit of feeling their pulse

• Symptom based ECG recording • 12 lead, holter, PAR, 30 day recording

• Routine screening • B/P machines, Sports heart rate monitors, Smart phone apps

• Implantable devices • Pacemakers, ICDs

• Implantable loop recorders

Diagnosis of AF

• Conventional recording methods • Patient controlled devices

• I phone, hand held recorders

• 15 people identified with undiagnosed AF at risk of stroke (n=1000 screen)

• AF education/awareness raising • Cost-effective intervention

• Pharmacists well placed to deliver

education, screening and referral

AF prevalence 6.7% (67/1,000) Automated iECG for AF detection 98.5% sensitivity 91.4% specificity.

The incremental cost-effectiveness ratio* of extending iECG screening into the community $AUD5,988 per Quality Adjusted Life Year gained $AUD30,481 for preventing one stroke. * based on 55% warfarin prescription adherence

What investigations are needed once you think you have found AF? • ECG – remember its an ECG diagnosis – don’t forget the

masqueraders – the automatic analysis is often wrong…

• Bloods – exclude reversible causes e.g. intercurrent infection, thyrotoxicosis

• Assessment for causes

• Alcohol history and advice

• Echo – needed to determine valvular vs non-valvular, to assess LV function

• Can be hard to get • Clinical skills important here

Goals of Management in AF

Management of AF has two broad objectives:

• Relief of symptoms

• Prevention of complications, including thromboembolism (particularly stroke) and heart failure

These objectives can be achieved by:

• Lifestyle modification

• Risk-stratified antithrombotic therapy

• Rate control – Accept AF and make sure ventricular rate not to fast.

• Rhythm control- Strive to maintain SR with drugs, DC cardioversion and ablation

Management Principles of AF

20

Cornerstones of AF Management

Control of symptoms

Rate Control Anticoagulation Rhythm Control

Th

era

pe

uti

c G

oa

ls Control of symptoms

Treatment or prevention of Tachycardia Induced Cardiomyopathy (CMP)

Reduction in Hospitalizations

Reduction in Hospitalizations

Prevention of thromboembolism

Minimization of bleeding risk

Rate Control vs Rhythm Control

FAVOURING RATE CONTROL FAVOURING RHYTHM CONTROL

Persistant AF Paroxysmal AF or newly detected AF

Less symptomatic More symptomatic

Age ≥ 65 y Age < 65 y

Hypertension No hypertension

Previous failure of antiarrythmic drug

No previous failure of antiarrythmic drug

Patient preference Patient preference

Approach to selecting drug therapy for

ventricular rate control

The Causes of Ischaemic Stroke

25 Leyden JM, et al. Stroke. 2013;44(5):1226-1231.

Causes of Ischaemic Stroke

%

Small vessel disease 11

Large artery atherosclerosis

16

Cardio-embolic 42

Other causes 6

Undetermined 25

Strokes Due to AF: …are due to large artery cerebral occlusion and are associated with a doubling of poor outcome (death or non-fatal stroke) two weeks after

ischaemic stroke

International Stroke Trial. Lancet 1997; 349: 1569-1581

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

Dead at 2 weeks Dead at 6 months

Mo

rtal

ity without AF

with AF

Severe Disability Is Increased in Patients With Stroke due to AF

73.3

58.3

36.4

30 32.5

16.3 15.8

10.9

0

10

20

30

40

50

60

70

80

acute phase 3 months 6 months 12 months

Seve

re D

isab

ility

(%

of

stro

ke p

atie

nts

)

with AF

without AF

Lin HJ, et al. Stroke. 1996;27:1760-1764

Definition and Scores for CHADS2 and CHA2DS2-VASc

Score

CHADS2

Congestive HF 1

Hypertension 1

Age ≥75 y 1

Diabetes mellitus 1

Stroke/TIA/TE 2

Maximum score 6

CHA2DS2-VASc

Congestive HF 1

Hypertension 1

Age ≥75 y 2

Diabetes mellitus 1

Stroke/TIA/TE 2

Vascular disease (prior MI, PAD, or aortic plaque)

1

Age 65–74 y 1

Sex category (i.e., female sex)

1

Maximum score 9

CHA2DS

2-VASc Score

Stroke Risk %

0 0

1 1.3

2 2.2

3 3.2

4 4.0

5 6.7

6 9.8

7 9.6

8 12.5

9 15.2

Annual Stroke Risk

Stroke risk stratification in non valvular AF

Risk Factors Points

Hypertension (> 160 mm Hg systolic) 1

Abnormal renal or hepatic function 1-2

Stroke 1

Bleeding history or anemia 1

Labile INR (TTR < 60%) 1

Elderly (age > 75 years) 1

Drugs (antiplatelet, NSAID) 1-2

High risk (> 4%/year) ≥4

Moderate risk (2-4%/year) 2-3

Low risk (< 2%/year) 0-1

HAS-BLED Score Estimates risk of major bleeding for patients on anticoagulation for

atrial fibrillation

Risk of Major Bleeding Increases with the HAS-BLED Score1

0

2

4

6

8

10

12

14

0 1 2 3 4 5 6 7 8 9

Ble

ed

s p

er

10

0 p

ati

en

t-ye

ars

30 1. Pisters R, et al. CHEST. 2010;138(5):1093-1100. 2. Olesen JB, et al. J Thromb Haemost. 2011;9:1460-1467.

Bleeding Risk Category2

HAS-BLED Score

Low 0-1

Intermediate 2

High ≥ 3

What’s available?

• NOACs

• Warfarin

• LA appendage occlusion

• Surgery

Warfarin Complexity

• Multiple targets in clotting pathway (procoagulant and anticoagulant)

• Vitamin K interaction

• Genetic variability

• Near the centre of drug interaction universe

• Initiating dose is guesswork

• Narrow therapeutic window

Haemorrhage After Warfarin Initiation

• 125,195 patients with AF age 65 and over

• 5 year follow-up after commencing warfarin

• Overall haemorrhage rate was 3.8% (95% CI, 3.8-3.9%) per person-year

• First 30 days - major haemorrhage rate: • 11.8% (95% CI, 11.1-12.4%) per person-year, all patients

• 16.7 % (95% CI, 14.3-19.4%) - patients with CHADS2 of ≥ 4

• Subsequent follow-up period: • 8.7% (10,840) attended hospital for haemorrhage

• 18.1% (1,963) died in hospital, or within 7 days of being discharged 33 Gomes T, et al. CMAJ. 2013;185(2):E121-E127.

Simple things can be hard….

• Visiting for blood tests

• Phoning results through..

Narrow Therapeutic Range with VKA for AF

Target INR

(2.0-3.0)

<1.5 1.5–1.9 2.0–2.5 2.6–3.0 3.1–3.5 3.6-4.0 4.1-4.5 >4.5

0

20

40

60

80 Ev

ents

/ 1

00

0 p

atie

nt

year

s Intracranial haemorrhage

Ischaemic stroke

The anticoagulant effect of vitamin K antagonists are optimized when therapeutic doses are maintained within a very narrow range

Hylek EM, et al. N Eng J Med 2003; 349:1019-1026 International Normalised Ratio (INR)

Warfarin : a flawed and somewhat surprising survivor from the 60’s

Alternatives to Warfarin

• NOACS • Consider renal impairment

• Associated with lower risk of intracranial bleeding

• If INR is well controlled less benefit

• Left Atrial Appendage Occlusion • Numerous devices becoming available

• Two devices are TGA approved

• Only one has randomized data

• Growing registry data

LAA Closure (LAAC) Devices

LAA Clip

EXCLUDE Trial (completed)

• AtriClip Device was FDA

approved in 2010 for LAA closure • No specific indication for Stroke

Reduction ClinicalTrials.gov identifier: NCT00779857

PLAATO WATCHMAN™

Device ACP

Surgical Ligation

“Safety and Efficacy of Left Atrial

Appendage Occlusion Devices”

Observational Study (retrospective) • To compare LARIAT® vs. WATCHMAN™

• LARIAT currently does not have a specific

indication for LAA Closure or Stroke

Reduction ClinicalTrials.gov identifier: NCT01695564

Stroke Treatment Options: LAA Ligation,

LAA Clips and LAA Closure

• First LAAC

device

(2001)

• Device no

longer

available

• Only LAAC device with 2

Randomized Controlled

Trials

• FDA approved with specific

indication to reduce the risk

of thromboembolism ClinicalTrials.gov identifiers:

NCT00129545 (PROTECT AF)

NCT01182441 (PREVAIL)

• US Trial halted in

2013

• AMPLATZER™

Cardiac Plug

Clinical Trial

ClinicalTrials.gov identifier:

NCT01118299

SH-230506-AD June15

Meta-Analysis Shows Comparable Primary Efficacy Results to Warfarin

Source: Holmes DR, et al. Holmes, DR et al. JACC 2015; In Press. Combined data set of all PROTECT AF and PREVAIL WATCHMAN patients versus chronic warfarin patients

HR p-value

Efficacy 0.79 0.22

All stroke or SE 1.02 0.94

Ischemic stroke or SE 1.95 0.05

Hemorrhagic stroke 0.22 0.004

Ischemic stroke or SE >7 days 1.56 0.21

CV/unexplained death 0.48 0.006

All-cause death 0.73 0.07

Major bleed, all 1.00 0.98

Major bleeding, non procedure-related 0.51 0.002

0.01 0.1 1 10

Favors WATCHMAN Favors warfarin

Hazard Ratio (95% CI)

SH-230506-AD June15

Role of LA appendage occlusion

• Think about it for patients who: • Can’t have anticoagulation

• High CHADSVASC and High HASBLED score

• Stroke despite adequate anticoagulation

• Need referral to Cardiologist

42

Annual risk

of

stro

ke, %

Stroke Risk Persists Even in Asymptomatic/Intermittent AF

• The risk of stroke with asymptomatic or intermittent AF is comparable to that with permanent AF1,2

1. Hart RG, et al. J Am Coll Cardiol 2000;35:183–7 2. Flaker GC, et al. Am Heart J 2005;149:657–63

Observed rate of ischaemic stroke1

Stroke risk category Low Moderate High

0

2

4

6

8

10

12

14

Intermittent AF

Sustained AF

ESC 2012 Guidelines: Selection of Patients for Anticoagulation1

Non-valvular atrial fibrillation Valvular atrial fibrillation

< 65 years and lone AF including women

Stroke risk assessment using CHA2DS2-VASc

0 1 ≥2

Assess bleeding risk (HAS-BLED score);

consider patient values/preferences

Novel oral anticoagulants:

rivaroxaban, dabigatran

apixaban

Vitamin K antagonist No antithrombotic therapy

Oral anticoagulant

Yes

1. Camm AJ et al. Eur Heart J 2012;33:2719–47.

Adapted from Camm, 20121

Are the New Agents Better than Warfarin?

• More effective

• Safer

• Good for Rural patients

• No blood tests

• Reversal agents available

48

Choosing between NOACs Characteristic Considerations Suggested NOAC

HAS-BLED ≥3 Agent/dose with lowest bleeding incidence

Dabigatran 110 mg Apixaban

Previous GI bleeding, or current high risk

Agent with lowest reported GI bleeding incidence

Apixaban

High risk of ischaemic stroke, low bleeding risk

Agent/dose with best ischaemic stroke reduction

Dabigatran 150 mg

Previous stroke Best-investigated agent or greatest reduction of secondary stroke

Rivaroxaban Apixaban

CAD, previous MI or high-risk for ACS/MI

Agent with a positive effect in ACS Dabigatran 150mg Rivaroxaban

Renal impairment Agent less dependent on renal clearance

Rivaroxaban Apixaban

Reversal Agent Rural communities Dabigatran

ACS: acute coronary syndromes; CAD: coronary artery disease; GI: gastrointestinal; MI: myocardial infarction Savelieva I & Camm AJ. Clin Cardiol 2014;37:32–47.

What is non-valvular AF?

• Atrial fibrillation in the setting of which valvular problem(s) is an example of non-valvular atrial fibrillation

• A) Mild tricuspid regurgitation

• B) Moderate to severe aortic regurgitation

• C) Mild mitral stenosis

• D) A bioprosthetic aortic valve

• E) All of the above

What is non-valvular AF?

• Atrial fibrillation in the setting of which valvular problem(s) is an example of non-valvular atrial fibrillation

• A) Mild tricuspid regurgitation

• B) Moderate to severe aortic regurgitation

• C) Mild mitral stenosis

• D) A bioprosthetic aortic valve

• E) All of the above

What is Non-valvular atrial fibrillation

• Valvular AF • Mechanical prosthetic valve

• Haemodynamically significant Mitral Stenosis (moderate or severe)

When Does the Risk of Bleeding Outweigh the Risk of Stroke?

• In more than 99% of patients the risk of ischaemic stroke is greater than the risk of bleeding on anticoagulants

• Anticoagulation may be associated with a net disadvantage in a small number of patients with a truly low risk of stroke (CHA2DS2-VASc = 0) who have a moderately elevated bleeding risk (HAS-BLED = 1-2)

Friberg L, et al. Circulation. 2012;125(19):2298-2307.

Who Not to Anticoagulate

• Definitely not1,2,3,4

• Clinically significant active bleeding • Drug allergy/hypersensitivity

• Probably or possibly not1,2,3,4

• CHA2DS2-VASc = 05

• Significant comorbid disease (cardiac, hepatic, renal) • Uncontrolled hypertension • Advanced age • Previous haemorrhagic event • Active drug / alcohol abuse 1. Product information, Eliquis® (apixaban), most recent amendment 29th of April 2013.

2. Product information, Pradaxa® (dabigatran etexilate), most recent amendment 25th January 2013. 3. Product information, Xarelto® (rivaroxaban), most recent amendment 3rd of April 2012. 4. Product information, Coumadin (warfarin), most recent amendment 11th of July 2006. 5. Friberg L, et al. Circulation. 2012;125:2298-2307.

54

Reversal agents – current and in development

• Idarucizumab (Praxbind) – Bunbury, Narrogin, Geraldton, Kalgoorlie

• Andexanet alfa (AnXa, PRT064445)

• Aripazine (Perosphere, PER977)

55

Idarucizumab • Anti-dabigatran humanized Fab

developed by Boehringer Ingelheim1

• Reduces blood loss and mortality in dabigatran-anticoagulated animal model2

• Phase III trial RE-VERSE AD: A Study of the RE-VERSal Effects of Idarucizumab on Active Dabigatran

• Real world experience is encouraging

FDA: Food and Drugs Agency (USA) 1. van Ryn J et al. Circulation 2012;126:A9928. 2. Honickel M et al. Crit Care 2014;18(Suppl 1):P99. 3. ClinicalTrials.gov NCT02104947.

Fully humanized antibody fragment

(Fab)

So… are there differences?

• All people are similar so treatment options are the same – i.e. same considerations and contraindications to medications regardless of where we live

• But…. • Access to healthcare is different

• Jobs are different and may be isolated without phone signal etc

• Simple things are harder

• Testing may be harder

Special Rural circumstances…

Simple advice can make the difference in emergencies

RFDS?

• Should all RFDS planes carry Idaruciximab?

• Give for industrial accidents when transfer to hospitals may take time – may be life saving

• Snake bites – may be life saving

What’s on the horizon?

One stop AF clinics from Heartcare

• Diagnosis

• Echo

• Testing for ischemia

• Management plans

• Same day DCCV if appropriate (pre-arranged after d/w GP)

ECG App

• Enables reliable live reporting of ECGs

• Advice while your patient still with you

So… When considering AF, is it a disadvantage to live in a Rural

community?

I know where I’d rather live…

Thank you