Atrial fibrillation: Assessment and Management of Risk of Stroke

Transcription

1 Atrial fibrillation: Assessment and Management of Risk of Stroke Dr Matthew Fay GP Principal The Willows Medical Practice- Queensbury GPwSI and Co-Founder Westcliffe Cardiology Service GP Partner Westcliffe Medical Group

2 Declaration of interests Funding has be variously given by: Abbot, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Dawn 4S, INRStar, Medtronic, Oberoi Consulting, Pfizer, Roche, Sanofi-Aventis, Servier I am an advisor to: Anticoagulation Europe, AF Association, Arrhythmia Alliance, Heart Valve Voice, National Stroke Association, Syncope Trust I am a trustee of LifeBlood

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4 1 National Clinical Guideline Centre Document information (draft for consultation) Venous t hromboembolic Rivaroxaban for the diseases: t he management treatment of deep of vein venous t hromboembolic thrombosis and prevention of Issued: March 2013 diseases and the recurrent role ofdeep vein thrombophilia t hrombosis testing and NICE quality pulmonary standard 29 guidance.nice.org.uk/qs29 embolism Issued: July 2012 NICE clinical guideline 144 NICE technology appraisal guidance 261 guidance.nice.org.uk/ta261 Atrial Fibrillation Quality standard Atrial for fibrillation: diagnosis the and management of atrial fibrillation management of venous t hromboembolic diseases Clinical guideline Methods, evidence and recommendations January 2014 Draft for Consultation Commissioned by the National Institute for Health and Care Excellence NHS Evidence has accredited the process used by the Centre for Health Technology Evaluation at NICE to produce technology appraisals guidance. Accreditation is valid for 5 years from September 2009 and applies to guidance produced since June 2008 using the processes described in NICE's 'The guide to the methods of technology appraisal' (2008). More information on accreditation can be viewed at NICE 2012 NICE 2013

5 Learning Points Screening Stroke Risk assessment Bleeding risk assessment Intervention Anti-platelets Anticoagulants Left Atrial Appendage occlusion Quality Stanard

6 Diagnosis of AF Personalised package of care and information Stroke prevention Symptomatic Asymptomatic Rate control strategies Symptomatic Rhythm Control Strategy Ablation strategies On-going annual assessment Nice AF Guideline DRAFT: January 2014 NICE AF Guideline June 2014

7 Screening

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9 Diagnosis of Atrial Fibrillation Perform pulse palpation to assess for the presence of an irregular pulse which may suggest AF in people presenting with: breathlessness or dyspnoea, Palpitations Syncope Dizziness Chest discomfort Stroke or transient ischaemic attack Perform an ECG to confirm the diagnosis of AF NICE AF Guideline June 2014

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12 Screening RCP Edinburgh AF Consensus Statement

13 Screening for Atrial Fibrillation in People aged 65 and over A report for the National Screening Committee May 2014

14 What is PAF?

15 Pacemaker Interrogation

16 Pacemaker Interrogation

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20 Stroke Risk

21 Stroke risk in AF: CHADS 2 CHADS 2 risk criteria Score Cardiac failure 1 Hypertension 1 Age >75 yrs 1 Diabetes mellitus 1 Stroke or TIA (previous history) 2

22 CHADS 2 Stroke Risk per 100 Person Years/Warfarin treatment Interpretation CHADS 2 risk criteria On Warfarin Not on Warfarin 0 Points Point Points Points Points Points

23 Stroke risk in AF: CHA 2 DS 2 VASc CHA 2 DS 2 VASc risk criteria Score Cardiac failure 1 Hypertension 1 Age >75 yrs 2 Diabetes mellitus 1 Stroke or TIA (previous history) 2 Vascular disease (IHD, PAD) 1 Age >75 yrs 1 Sex Category 1

24 AF PIE: FUTURE AF PIE: PAST Fuster V. Circulation 2012; epubl April 18

25 Over Simplification?

26 Independent Predictors of Stroke in AF Systematic Review Significant by Multivariate Analysis Adjusted Relative Risk (95% CI) Prior stroke or TIA 5 of 5 studies 2.5 ( ) Increasing age 6 of 6 studies 1.5/decade ( ) History of hypertension or systolic BP > 160 mm Hg 5 of 5 studies 2.0 ( ) Diabetes 4 of 4 studies 1.8 (1.5 22) Female gender 3 of 6 studies 1.6 ( ) Heart failure 0 of 4 studies* Not significant Coronary artery disease 0 of 4 studies Not significant * Significant in a subgroup of participants undergoing echocardiography in trials included AFI pooled analysis Hart RG et al. Neurology 2007; 69: 546.

27 Guidance on Risk Assessment and Stroke Prevention for Atrial Fibrillation: GRASP-AF Tools to support data collection and analysis for GRASP AF

28 The GRASP AF Tool Identifies patients with atrial fibrillation Searches for co-morbidities and works out CHADS2 score Searches for current medication- warfarin or aspirin (or both) Searches for recorded reasons for NOT treating with warfarin Has a comprehensive Advice sheet

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30 CHART Online data Data on 15 th October 2013: Number of practices uploading data: 2538 Number of patients with AF: 320,457 Prevalence of AF: 1.77% Percentage of patients CHADS 1: 83.96% Percentage of patients CHADS 1 on OAC: 46.29% Percentage of patients CHADS 1 on AP: 35.04%

31 CHART Online data Data on 23 rd June 2014: Number of practices uploading data: 8020 Number of patients with AF: 320,457 Prevalence of AF: 1.8% Percentage of patients CHADS 1: 84.0% Percentage of patients CHADS 1 on OAC: 57.5% Percentage of patients CHADS 1 on AP: 34.04%

32 CHART Online Data Number of practices Strokes saved Strokes saved if warfarin was 85% , ,523

33 AVERROES Apixaban (%) Aspirin (%) Assessment that INR could be maintained in therapeutic range X Assessment that INR could not or was unlikely to be measured at requested intervals X Uncertainty about patients ability to adhere to instructions regarding VKA Therapy X CHADS 2 score of 1 and VKA therapy not recommended by physician X Patients refusal to take VKA Multiple reasons for unsuitability of VKA therapy X

34 Cumulative Risk AVERROES: Stroke or SEE 5600 patients, 36 countries, 522 centres RR= %CI= p<0.001 ASA mg/d Apixaban mg bd No. at Risk Months ASA Apix

35 Cumulative Risk AVERROES - Major Bleeding RR= %CI= P= 0.56 Apixaban ASA Months No. at Risk ASA Apix N Engl J Med. 2011;364:

36 Bleeding Risk

37 Bleeding risk in AF: HAS-BLED HAS-BLED risk criteria Points awarded Hypertension (i.e. Uncontrolled BP) 1 Abnormal renal and liver function (1 point each) 1 or 2 Stroke 1 Bleeding 1 Labile INRs 1 Elderly (e.g. age >65 years, frail condition) 1 Drugs or alcohol (1 point each) 1 or 2 Maximum 9 points NICE AF Guideline June 2014

38 Frailty as a risk Prospective study of a cohort of 220 acute inpatients aged 70 years with AF Patients followed up at 6 months = 207 Frail = 130; Not Frail = 77 Warfarin (n=83) Antiplatelet (n=98) None (n=26) Haem Stroke Both Haem Stroke Both Haem Stroke Both Frail 30% 7% 37% 25% 9% 34% 8% 29% 38% Not Frail 19% 2% 21% 14% 5% 18% 0% 50% 50% Total 23% 4% 27% 22% 8% 31% 8% 31% 38% Age and Ageing 2009; 38: doi: /ageing/afn293

39 Dementia as a risk Some evidence to support worse control but not why (Circ Cardiovasc Qual Outcomes. 2010;3: doi: /CIRCOUTCOMES ) No trials identify any specific increased risk of complications Suggestions that dementia is more common in people with AF

40 Falls as a risk

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43 Falls as a risk Cost benefit analysis shows the number of falls on average likely to cause greater risk than benefits with warfarin = 295 Arch Intern Med. 1999;159(7): doi: /archinte Beware fallers with significant injury Major head injury with proven SDH Major bruising resulting in surgery

44 Using HAS-BLED in those with AF Do not use a HAS-BLED score to obstruct people accessing oral anticoagulation Use the HAS-BLED score to identify modifiable risk factors to reduce the bleeding risk such as: Control high blood pressure Improve warfarin control Consider alternatives to warfarin Stop concurrent medication, such as NSAID Advice about alcohol consumption NICE AF Guideline June 2014

45 Antiplatelet Use for Stroke Prevention in AF

46 Aspirin vs Placebo in Stroke Prevention in AF AFASAK-1 SPAF I EAFT ESPS-II LASAF, daily LASAF, alternate day UK-TIA, 300 mg daily UK-TIA, 1200 mg daily JAST Aspirin Trials SAFT ESPS II, Dipyridamole ESPS II, Combination All Trials Antiplatelet therapy reduces incidence of stroke by about 22% Hart R, et al. Ann Intern Med. 2007;146: % 50% 0% -50% -100% Favors Antiplatelet Favors Placebo/ Control

47 Aspirin effect vs group assignment (anticoagulation eligibility) in the SPAF-I study J Stroke Cerebrovasc Dis 1993; 3: Aspirin eligible AF patients Anticoagulation Eligible Group I Anticoagulation Ineligible* Group II Warfarin Aspirin (n=206) 1 event Placebo (n=211) 18 events Aspirin (n=346) 25 events Placebo (n=357) 28 events Group I Risk reduction 94% [P<0.001] Group II Risk reduction 8% [P=0.75] *based on safety considerations or refusal of anticoagulation SPAF I analysis Risk reduction 42% P=0.02

48 Vitamin K Oral Anticoagulant Use for Stroke Prevention in AF

49 Warfarin vs Placebo in Stroke Prevention in AF AFASAK-1 SPAF BAATAF CAFA SPINAF EAFT ALL Trials Warfarin reduces incidence of stroke by about 64% 100% 50% 0% -50% -100% Favors Warfarin Favors Placebo/ Control Hart R, et al. Ann Intern Med. 2007;146:

50 Percent of Patients Effective Anticoagulation Stroke Severity and Survival: National Acute Stroke Israeli Survey Patients with AF admitted with acute ischemic stroke or transient ischemic attack No Antithrobotic therapy (n = 89) Antiplatelet Therapy (n = 124) Warfarin INR < 2.0 (n = 63) Warfarin INR 2.0 (n = 48) 0 NIHSS Scale > 5 Rankin Scale 4-5 or Deceased NIHSS Scale: National Institutes of Health stroke scale (stroke severity on admission) Rankin Scale: Functional disability at discharge Schwammenthal Y, et al. Am J Cardiol. 2010;105: Month 3 Months 6 Months 1 Year Mortality

51 Cumulative survival Time in therapeutic range (TTR) matters Warfarin group % 61 70% 51 60% 41 50% 31 40% <30% Non warfarin Survival to stroke (days) Morgan CL et al. Thrombosis Research 2009;124:37 41.

52 Non Vitamin K Oral Anticoagulant Use for Stroke Prevention in AF

53 The perfect anticoagulant Effective Oral Fast onset of action Short half life Predictable pharmacokinetics No drug/food interactions Fully reversible Do the NOACs fulfill these criteria?

54 NOACs How do they work?

55 The Clotting Cascade:-Warfarin XII Contact Activation(Intrinsic) Pathway XIIa XI Prothrombi n (II) XIa IX VIIIa IXa Tissue Factor (Extrinsic) Pathway X Xa X V V a Fibrinogen (I) VII VII a Thrombin (IIa) Fibrin (Ia) Tissue Factor Cross linked Clot

56 The Clotting Cascade-Dabigatran XII Contact Activation(Intrinsic) Pathway XIIa Tissue Factor (Extrinsic) Pathway XI XIa IX IXa VII VII a VIIIa Tissue Factor X Xa X Prothrombi n (II) V V a Fibrinogen (I) Thrombin (IIa) Fibrin (Ia) Cross linked Clot

57 The Clotting Cascade-Apixaban, Edoxaban Rivaroxaban, XII Contact Activation(Intrinsic) Pathway XIIa Tissue Factor (Extrinsic) Pathway XI XIa IX VIIIa IXa X Xa X VII VII a Tissue Factor Prothrombi n (II) V V a Fibrinogen (I) Thrombin (IIa) Fibrin (Ia) Cross linked Clot

58 Indications and Dosing Dabigatran Rivaroxaban Apixaban Prevention of VTE post THR/TKR Prevention of CVA in AF Treatment of acute VTE 110mg bd 10mg od 2.5mg bd 150mg bd (110mg bd) 150mg bd 20mg od 15mg bd for 3/52 20mg od 5mg bd (2.5mg bd) 10mg bd for 7/7 5mg bd SPC Dabigatran, Rivaroxaban, Apixaban

59 Renal function Anticoagulant Creatinine clearance (ml/min) <15 Dabigatran 150mg bd (110mg bd) AVOID Rivaroxaban 15mg od 15mg od AVOID Apixaban 5mg bd 2.5mg bd AVOID

60 How do NOACs affect the coagulation screen?

61 Coagulation tests with Anticoagulant Drugs Test UFH LMWH Warfarin Rivaroxaban Apixaban Dabigatran PT - - /- -/ -/ APTT -/ -/ -/ Fibrinogen Thrombin Time Anti-Xa - - Haemoclot Rivaroxaban and Apixaban: The PT and APTT cannot be used to determine whether anticoagulant drug present

62 Switching from one anticoagulant to another

63 Switching from warfarin to NOAC Rivaroxaban Wait till INR < 3.0 AF Wait till INR < 2.5 DVT, PE Dabigatran Wait till INR < 2.0 Apixaban Wait till INR < 2.0

64 What to do if a dose of a NOAC is missed? Once daily regimens Take the forgotten dose up to 12hrs after time of usual intake Twice daily regimens Take the forgotten dose up till 6hrs after time of usual intake ESC Practical Guide on the use of NOAC 2013

65 Bleeding Local measures Stop NOAC temporarily Tranexamic acid Coagulation screen Renal function Discuss with haematologist if ongoing issue

66 Elective minor (when warfarin would not be stopped) Dabigatran Rivaroxaban Apixaban Minor dental work 12 hours post dose hours post dose >24 hours post dose Major dental work 24 hours post dose Next dose > 4 hours post procedure 24 hours post dose Next dose > 4 hours post procedure hours post dose Next dose > 4 hours post procedure Upper/lower Endoscopy + simple biopsy Cataract removal Joint injection 24 hours post dose Next dose > 4 hours post procedure 24 hours post dose Next dose > 4 hours post procedure hours post dose Next dose > 4 hours post procedure NHS GGC Guidance based on SPC Dabigatran, Rivaroxaban, Apixaban

67 Emergency Surgery and Bleeding

68 Warfarin Vitamin K IV 6 hours PO 24 hours Prothrombin complex concentrates (PCCs) Factors II, VII, IX, X Reversal within 30 minutes Can assess INR for effectiveness/safety

69 NOACs No specific reversal agent Well-adsorbed to activated charcoal give within two hour of swallowing Dialysis Dabigatran yes Rivaroxaban, apixaban no General principles Check coagulation screen Assess effect Check renal function Assess half life Products largely speculation/ based on non-clinical data off-licence use; safety issues (thrombosis)

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71 INR Vitamin K - no Immediate Effect on INR Schematic diagram showing effect of vitamin K on INR Vitamin K has a slow onset (>24 hours) 1 Vitamin K supports generation of normal, functioning clotting factors in the liver Effectivity of INR normalization depending on VKA used (different half-lifes; (from 9 11 hours for acenocoumarol, to hours for phenprocoumon) 1,2 4 Vitamin K injection PD profile (INR) of VKA t ½ of VKA ~4 5 days 3 PD profile (INR) after administration of vitamin K 2 Day 1 Day 2 1. Heidbuchel et al, 2013; 2. Scharf et al, 2009

72 Schematic diagram Emergencies in Anticoagulated Patients Schematic diagram showing PK/PD characteristics of VKA and rivaroxaban Reversal strategies may be required if action of drug is long and needs to be antagonized in emergency situations t ½ of VKA ~4 5 days PD profile (INR) of VKA PK/PD profile of rivaroxaban t ½ of rivaroxaban 5 9 hours (young) or hours (elderly) Day 1 Day 2 PD, pharmacodynamic; PK, pharmacokinetic; t ½, half-life 1. Makris et al, 2012; 2. Kubitza et al, 2005; 3. Kubitza et al, 2008

73 PT in seconds Rivaroxaban-Induced Anticoagulation Reversal with PCC Placebo PCC 20 mg rivaroxaban was administered bid for 2.5 days followed by PCC (Prothrombin Complex Concentrate - Cofact, 50 U/kg body weight) Prolongation of PT was reversed completely by PCC 10 ETP was reversed by PCC with an overshoot in effects PCC Rivaroxaban (2.5 days) Time Limitation PT agent used showed low sensitivity to rivaroxaban Prolongation of PT in this study was approximately 4 seconds at maximum Eerenberg et al. Circulation 2011;124:

74 Specific Reversal Agents for Non-VKA Oral Anticoagulants Company Compound Factor Xa inhibitor Reversal for: Factor IIa inhibitor LMWH/ fondaparinux Status Portola Pharmaceuticals PRT064445/ (andexanet alfa) Universal No Yes (antithrombinmediated Factor Xa inhibition) Phase II completed One phase III with apixaban completed; rivaroxaban and edoxaban - onngoing Boehringer Ingelheim BI (idarucizumab) No Specific for dabigatran No Phase I completed; 3 phase III started 4 Perosphere, Inc. PER977 (aripazine) Universal Universal Universal Phase I completed 5

75 Created 10/1/2015 Dr. Matthew Fay: Westcliffe Medical Group Practical Considerations

76 Starting a patient on a NOAC Check patient is not taking interacting drugs Counsel patient: it is an anticoagulant Head injury, trauma, melaena, significant GI bleed, prolonged epistaxis, large ecchymoses/ haematoma Compliance- important to take as advised (od Rivaroxaban, bd Apixaban, bd Dabigatran) Baseline FBC, renal and liver function

77 Summary of use of NOACs Benefits of novel anticoagulants But Non inferior/superior to warfarin More stable anticoagulation (in patients poorly controlled on warfarin) Shorter half life No requirement for anticoagulant monitoring Fewer drug-drug interactions No food-drug interactions Less intracranial bleeding Limited reversal options Increased drug costs compared to warfarin Current lack of familiarity

78 Monitoring of Anticoagulants Created 10/1/2015 Dr. Matthew Fay: Westcliffe Medical Group

79 Left Atrial Appendage Occlusion for Stroke Prevention in AF

80 Stroke Prophylaxis in AF Difficulties with Warfarin use Frequent Monitoring Difficulty in Compliance (TTR 48-63%) Drug / Diet Interactions Bleeding Risk (ICH) Risks in Elderly (Falls, Poly-pharmacy) Autopsy & TEE data implicate LAA LAA Closure Devices Watchman Barbs Engage LAA Wall 160 µ PET fabric

81 NICE Clinical Guideline 180 and Stroke Prevention in AF

82 Diagnosis of AF Personalised package of care and information Stroke prevention Symptomatic Asymptomatic Rate control strategies Symptomatic Rhythm Control Strategy Ablation strategies On-going annual assessment Nice AF Guideline DRAFT: January 2014 NICE AF Guideline June 2014

83 Stroke Risk stratification CHADSVASc Score Bleeding risk stratification Do not offer Antiplatelet Therapy Offer Anticoagulation to those at risk of AF related stroke Anticoagulation offered Anticoagulation contra-indicated Discuss the options for anticoagulation with the person and base the choice on their clinical features and preferences Vit K antagonists Assessment of A/C control Poor control Non Vit K antagonists Left atrial appendage occlusion Annual review in all patients NICE AF Guideline June 2014

84 Venous Atrial thromboembolic fibrillation: treatment and diseases: management the management of venous thromboembolic diseases and the role of thrombophilia testing Issued: July 2015 NICE quality standard 93 guidance.nice.org.uk/qs93 Deep vein thrombosis June 2012 NICE 2015

85 NICE Quality Standard 93 Statement 1 Adults with non-valvular atrial fibrillation and a CHA 2 DS 2 -VASc stroke risk score of 2 or above are offered anticoagulation

86 NICE Quality Standard 93 Statement 2 Adults with atrial fibrillation are not prescribed aspirin monotherapy for stroke prevention

87 NICE Quality Standard 93 Statement 3 Adults with atrial fibrillation who are prescribed anticoagulation discuss the options with their healthcare professional at least once a year.

88 NICE Quality Standard 93 Statement 4 Adults with atrial fibrillation taking a vitamin K antagonist who have poor anticoagulation control have their anticoagulation reassessed

89 NICE Quality Standard 93 Statement 5 Adults with atrial fibrillation whose treatment fails to control their symptoms are referred for specialised management within 4 weeks

90 NICE Quality Standard 93 Statement 6 (Developmental) Adults with atrial fibrillation on long term vitamin K antagonist therapy are supported to self-manage with a coagulometer

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92 Fig 2 Cumulative incidences for major adverse cardiovascular event during two year followup for patients receiving warfarin versus no oral anticoagulant. Ying Xian et al. BMJ 2015;351:bmj.h by British Medical Journal Publishing Group

93 Fig 3 Major adverse cardiovascular event (MACE) and home time according to warfarin treatment at discharge, overall and in clinically relevant subgroups. Ying Xian et al. BMJ 2015;351:bmj.h by British Medical Journal Publishing Group

94 Summary Points Screening Stroke Risk assessment Bleeding risk assessment Intervention Anticoagulants Left Atrial Appendage occlusion Quality Standard

95 Thank you for your