Atrial Fibrillation in the Rural Community is it any different? Dr Allison Morton Heartcare WA SJOG Bunbury
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1 Atrial Fibrillation in the Rural Community is it any different? Dr Allison Morton Heartcare WA SJOG Bunbury
2 People? Spot the difference
3 What about the location?
4 Equipment?
5 Hazards?
6 So are there differences? People No Location Yes Equipment Yes Hazards - Yes
7 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 By 2034, AF prevelance expected to be over 600,000 patients Ball et al. MJA 202 (1) 19 January
9 Epidemiology 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 y, and upto 35 cases per 1000/yr between age of 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
10 Pathophysiology Extracardiac Factors: Hypertension Obesity Sleep apnea Hyperthyroidism Alcohol/drugs Atrial Structural Abnormalities: Fibrosis Dilation Ischemia Infiltration Hypertrophy Inflammation Oxidative stress Atrial tachycardia remodeling AF RAAS activation Genetic Variants: Channelopathy Cardiomyopathy Atrial Electrical Abnormalities: Heterogeneity Conduction Action potential duration/refractoriness Automaticity Abnormal intracellular Ca ++ handling Autonomic nervous system activation
11 What makes someone have AF? alcohol, infection, ischaemia, post surgery, thyrotoxicosis Substrate Triggers Age, hypertension, OSA,alcohol, IHD,weight etc
12 Diagnosis? Is this a clinical diagnosis? What do you need to be diagnosed with AF?
13 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
14 Diagnosis of AF Conventional recording methods Patient controlled devices I phone, hand held recorders
15 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
16 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
17 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
18 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
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20 Therapeutic Goals Management Principles of AF Cornerstones of AF Management Rate Control Rhythm Control Anticoagulation Control of symptoms Control of symptoms Prevention of thromboembolism Treatment or prevention of Tachycardia Induced Cardiomyopathy (CMP) Reduction in Hospitalizations Minimization of bleeding risk Reduction in Hospitalizations 20
21 Rate Control vs Rhythm Control FAVOURING RATE CONTROL Persistant AF Less symptomatic Age 65 y Hypertension Previous failure of antiarrythmic drug Patient preference FAVOURING RHYTHM CONTROL Paroxysmal AF or newly detected AF More symptomatic Age < 65 y No hypertension No previous failure of antiarrythmic drug Patient preference
22 Approach to selecting drug therapy for ventricular rate control
23
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25 The Causes of Ischaemic Stroke Causes of Ischaemic Stroke % Small vessel disease 11 Large artery atherosclerosis 16 Cardio-embolic 42 Other causes 6 Undetermined 25 Leyden JM, et al. Stroke. 2013;44(5):
26 Mortality 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 45% 40% 35% 30% 25% 20% without AF with AF 15% 10% 5% 0% Dead at 2 weeks Dead at 6 months International Stroke Trial. Lancet 1997; 349:
27 Severe Disability (% of stroke patients) Severe Disability Is Increased in Patients With Stroke due to AF with AF without AF acute phase 3 months 6 months 12 months Lin HJ, et al. Stroke. 1996;27:
28 Stroke risk stratification in non valvular AF Definition and Scores for CHADS 2 and CHA 2 DS 2 -VASc Score CHADS 2 Congestive HF 1 Hypertension 1 Age 75 y 1 Diabetes mellitus 1 Stroke/TIA/TE 2 Maximum score 6 CHA 2 DS 2 -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 y 1 Sex category (i.e., female sex) 1 Maximum score 9 Annual Stroke Risk CHA 2 DS 2-VASc Score Stroke Risk %
29 HAS-BLED Score Estimates risk of major bleeding for patients on anticoagulation for atrial fibrillation 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
30 Bleeds per 100 patientyears Risk of Major Bleeding Increases with the HAS-BLED Score Bleeding Risk Category 2 HAS-BLED Score Low 0-1 Intermediate 2 High Pisters R, et al. CHEST. 2010;138(5): Olesen JB, et al. J Thromb Haemost. 2011;9:
31 What s available? NOACs Warfarin LA appendage occlusion Surgery
32 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
33 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, %) per person-year First 30 days - major haemorrhage rate: 11.8% (95% CI, %) per person-year, all patients 16.7 % (95% CI, %) - patients with CHADS 2 of 4 Subsequent follow-up period: 8.7% (10,840) attended hospital for haemorrhage Gomes T, et al. CMAJ. 2013;185(2):E121-E % (1,963) died in hospital, or within 7 days of being discharged
34 Simple things can be hard. Visiting for blood tests Phoning results through..
35 Events / 1000 patient years Narrow Therapeutic Range with VKA for AF 80 Ischaemic stroke Intracranial haemorrhage Target INR ( ) The anticoagulant effect of vitamin K antagonists are optimized when therapeutic doses are maintained within a very narrow range 20 0 < >4.5 International Normalised Ratio (INR) Hylek EM, et al. N Eng J Med 2003; 349:
36 Warfarin : a flawed and somewhat surprising survivor from the 60 s
37 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
38
39 Stroke Treatment Options: LAA Ligation, LAA Clips and LAA Closure LAA Closure (LAAC) Devices PLAATO First LAAC device (2001) Device no longer available WATCHMAN Device Only LAAC device with 2 Randomized Controlled Trials FDA approved with specific indication to reduce the risk of thromboembolism ClinicalTrials.gov identifiers: NCT (PROTECT AF) NCT (PREVAIL) ACP US Trial halted in 2013 AMPLATZER Cardiac Plug Clinical Trial ClinicalTrials.gov identifier: NCT LAA Clip EXCLUDE Trial (completed) AtriClip Device was FDA approved in 2010 for LAA closure No specific indication for Stroke Reduction ClinicalTrials.gov identifier: NCT 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: NCT SH AD June15
40 Meta-Analysis Shows Comparable Primary Efficacy Results to Warfarin HR p-value Efficacy All stroke or SE Ischemic stroke or SE Hemorrhagic stroke Ischemic stroke or SE >7 days CV/unexplained death All-cause death Major bleed, all Major bleeding, non procedure-related Favors WATCHMAN Favors warfarin Hazard Ratio (95% CI) 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 SH AD June15
41 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 stroke, % Stroke Risk Persists Even in Asymptomatic/Intermittent AF The risk of stroke with asymptomatic or intermittent AF is comparable to that with permanent AF 1, Observed rate of ischaemic stroke 1 Low Moderate High Stroke risk category Intermittent AF Sustained AF 1. Hart RG, et al. J Am Coll Cardiol 2000;35: Flaker GC, et al. Am Heart J 2005;149:
43 ESC 2012 Guidelines: Selection of Patients for Anticoagulation 1 Non-valvular atrial fibrillation Valvular atrial fibrillation Yes < 65 years and lone AF including women Stroke risk assessment using CHA 2 DS 2 -VASc Oral anticoagulant Assess bleeding risk (HAS-BLED score); consider patient values/preferences No antithrombotic therapy Adapted from Camm, Novel oral anticoagulants: rivaroxaban, dabigatran apixaban Vitamin K antagonist 1. Camm AJ et al. Eur Heart J 2012;33:
44 Are the New Agents Better than Warfarin? More effective Safer Good for Rural patients No blood tests Reversal agents available
45
46
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48 Choosing between NOACs Characteristic Considerations Suggested NOAC HAS-BLED 3 Previous GI bleeding, or current high risk High risk of ischaemic stroke, low bleeding risk Previous stroke CAD, previous MI or high-risk for ACS/MI Renal impairment Agent/dose with lowest bleeding incidence Agent with lowest reported GI bleeding incidence Agent/dose with best ischaemic stroke reduction Best-investigated agent or greatest reduction of secondary stroke Agent with a positive effect in ACS Agent less dependent on renal clearance Dabigatran 110 mg Apixaban Apixaban Dabigatran 150 mg Rivaroxaban Apixaban Dabigatran 150mg Rivaroxaban 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:
49 What is non-valvular AF? Atrial fibrillation in the setting of which valvular problem(s) is an example of non-valvular atrial fibrillation A) B) C) D) E) Mild tricuspid regurgitation Moderate to severe aortic regurgitation Mild mitral stenosis A bioprosthetic aortic valve All of the above
50 What is non-valvular AF? Atrial fibrillation in the setting of which valvular problem(s) is an example of non-valvular atrial fibrillation A) B) C) D) E) Mild tricuspid regurgitation Moderate to severe aortic regurgitation Mild mitral stenosis A bioprosthetic aortic valve All of the above
51 What is Non-valvular atrial fibrillation Valvular AF Mechanical prosthetic valve Haemodynamically significant Mitral Stenosis (moderate or severe)
52 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 (CHA 2 DS 2 -VASc = 0) who have a moderately elevated bleeding risk (HAS-BLED = 1-2) Friberg L, et al. Circulation. 2012;125(19):
53 Who Not to Anticoagulate Definitely not 1,2,3,4 Clinically significant active bleeding Drug allergy/hypersensitivity Probably or possibly not 1,2,3,4 CHA 2 DS 2 -VASc = 0 5 Significant comorbid disease (cardiac, hepatic, renal) Uncontrolled hypertension Advanced age Previous haemorrhagic event Active 1. drug Product information, / alcohol Eliquis (apixaban), abuse most recent amendment 29 th of April Product information, Pradaxa (dabigatran etexilate), most recent amendment 25 th January Product information, Xarelto (rivaroxaban), most recent amendment 3 rd of April Product information, Coumadin (warfarin), most recent amendment 11 th of July Friberg L, et al. Circulation. 2012;125:
54 Reversal agents current and in development Idarucizumab (Praxbind) Bunbury, Narrogin, Geraldton, Kalgoorlie Andexanet alfa (AnXa, PRT064445) Aripazine (Perosphere, PER977) 54
55 Idarucizumab Anti-dabigatran humanized Fab developed by Boehringer Ingelheim 1 Reduces blood loss and mortality in dabigatran-anticoagulated animal model 2 Phase III trial RE-VERSE AD: A Study of the RE-VERSal Effects of Idarucizumab on Active Dabigatran Real world experience is encouraging Fully humanized antibody fragment (Fab) FDA: Food and Drugs Agency (USA) 1. van Ryn J et al. Circulation 2012;126:A Honickel M et al. Crit Care 2014;18(Suppl 1):P ClinicalTrials.gov NCT
56 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
57 Special Rural circumstances
58 Simple advice can make the difference in emergencies
59 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 RFDS?
60 What s on the horizon? One stop AF clinics from Heartcare ECG App Diagnosis Echo Testing for ischemia Management plans Same day DCCV if appropriate (pre-arranged after d/w GP) Enables reliable live reporting of ECGs Advice while your patient still with you
61 So When considering AF, is it a disadvantage to live in a Rural community?
62 I know where I d rather live
63 Thank you
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