Modern Management in Primary Care (AF1)

Transcription

1 Modern Management in Primary Care (AF1) Dr Ravi Assomull Consultant Cardiologist London North West Healthcare NHS Trust Dr Yassir Javaid Primary Care Cardiovascular Lead East Midlands Strategic Clinical Network

2 Setting the Scene.. AF massively increases stroke risk Increases stroke risk by 430% Increases stroke risk by 480% Increases stroke risk by 340% Increases stroke risk by 240%

3 % of patients Stroke severity in patients with AF Effect of first ischemic stroke in patients with AF (n=597) 1 60% 50% 40% 30% 20% 10% 0% Gladstone DJ et al. Stroke. 2009; 40: Disabling Fatal

4 Annual risk of stroke (%) AF Related Strokes Are More Severe Among patients who had a stroke, those with AF experienced a: 70% increase in in-hospital mortality ** 40% decrease in the relative chance of discharge to own home 20% increase in the length of hospital stay compared to those without AF *The Copenhagen stroke study, a prospective community-based study. n=1,197 **In hospital mortality: 72 deaths, n=217 with AF vs. 171 deaths n=968 without AF Discharge to own home: n=104 with AF vs. 662 deaths n=968 without AF Length of hospital stay: 50.4 days with AF vs days without AF Jorgensen, et al. Stroke 1996;27: Stroke risk similar in persistent and paroxysmal AF The risk of stroke with asymptomatic or paroxysmal AF is comparable to that with persistent AF 14 Intermittent AF Low Moderate High Stroke risk category Sustained AF Journal of the American College of Cardiology volume 35, Issue 1, January 2000, Pages

5 NICE Guideline for AF (June 2014) Do not offer aspirin monotherapy for AF related stroke prevention See NICE CG180 for full guideline Risks of a Fall While on Warfarin Absolute risk of subdural haematoma: 0.04%/yr Relative risk (RR) of subdural hematoma in someone who falls vs. someone who doesn t: 1.4 RR of subdural hematoma in faller on warfarin vs. faller not on warfarin: 3.3 So... Would need to fall 295 times a year to outweigh the benefits of warfarin (regardless of age/baseline stroke risk) Man-Son-Hing M, et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. Arch Intern Med. 1999;159(7): Tinetti ME, SpeechleyM, Ginter SF. Risk Factors for Falls among Elderly Persons Living in the Community. N Engl J Med 1988; 319(26):

6 NICE Guideline for AF (June 2014) Do not withhold anticoagulation solely because of risk of having a fall Stroke Prevention in AF.

7 NICE Guideline for AF (June 2014) CHA 2 DS 2 VASc for all patients: Paroxysmal Persistent Permanent Atrial flutter Risk of recurrence after cardioversion back to sinus rhythm If CHA 2 DS 2 VASc 2 offer anticoagulation If CHA 2 DS 2 VASc = 1 consider anticoagulation Offer = confident that for the vast majority of pts an intervention will do more good than harm and be cost-effective Consider = confident that for most pts an intervention will do more good than harm and be cost-effective Who should be anticoagulated? (ESC 2012) Yes Non-valvular AF <65 years & lone AF (including female) No Assess risk of stroke (CHA 2 DS 2 -VASc score) Valvular AF* VKA *AF related to rheumatic valvular disease (predmoninantly MS) and prosthetic valve OAC therapy No antithrombotic therapy Assess bleeding risk (HAS-BLED score) Consider patient values and preferences NOAC** VKA ** NOAC broadly preferable to VKA (INR 2 3) for most patients with non-valvular AF Adapted from Camm et al. Eur Heart J 2012;e-published August 2012, doi: /eurheartj/ehs253.

8 ESC 2016 Recommendations Eur Heart J doi: /eurheartj/ehw210. NICE Guideline for AF (June 2014) Anticoagulation may be with apixaban, dabigatran, rivaroxaban or a vitamin K antagonist Discuss the options for anticoagulation with each patient and base the choice on their clinical features and preferences If anticoagulation is not tolerated or contraindicated consider left atrial appendage occlusion (LAAO)

9 Valvular vs non-valvular AF Lip et Al Europace doi: /europace/euv309

10 Annual event rate Annual event rate The risk of ischaemic stroke "without" OAC exceeds the risk of intracranial bleeding "with" OAC* 18% 16% Relation between risk scores and annual event rates of 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 ( ) CHA 2 DS 2 -VASc score 18% 16% HAS-BLED score 14% 12% 10% Stroke [no OAC] 14% 12% 10% Stroke [no OAC] Stroke [OAC] 8% Stroke [OAC] 8% 6% 6% 4% 2% ICH [no OAC] ICH [OAC] 0% Score Adapted from Friberg et al. Circulation 2012;125: % 2% 0% ICH [OAC] ICH [no OAC] Score *Except those with a very low risk of stroke HAS-BLED score Letter Clinical characteristic Points awarded H Hypertension (SBP > 160mmHg) 1 A Abnormal renal and liver function (1 point each) (Creat >200; Br >x2; ALP/AST>x3) 1 or 2 S Stroke 1 B Bleeding diathesis (Prev bleed/unexplained anaemia) 1 L Labile INRs 1 E Elderly (age >65 years) 1 D Drugs or alcohol (1 point each) ( 8 drinks/week) 1 or 2 Maximum 9 points

11 *This table is based on the likely risk / benefit of warfarin in NVAF patients. The NOACs have been shown to be at least non-inferior to warfarin in terms of reducing ischaemic stroke in NVAF patients. Dabigatran 150mg has actually been shown to be superior to warfarin in reducing ischaemic stroke. The NOACs have been shown to be not significantly more hazardous than warfarin in terms of causing major bleeds in NVAF patients. Dabigatran 110mg, apixaban 5mg and edoxaban 60mg have actually been shown to be associated with significantly fewer major bleeds than warfarin. Adapted from NICE: Patient Decision Aid Atrial Fibrillation: medicines to help reduce your risk of a stroke what are the options; June 2014 Cardiac rhythm assessment MANUAL pulse checking will give a strong clue to rhythm Now often ignored! Is it regular? Does the strength of pulse vary? What is the rate? ECG to monitor or confirm rhythm

12 SAFE Trial Fitzmaurice BMJ 2007(25 August) Objectives: Does screening improve detection of AF in primary care? Opportunistic vs Systematic screening Design: Multicentred Primary Care RCT across 50 practices in England Participants: patients 65 yrs in 25 intervention and 25 control practices Results: Detection rate/year of new AF cases: 1.63% (screening practices) vs 1.04% (control practices) (difference 0.59%, 95% CI 0.20% to 0.98%). Systematic vs opportunistic screening detected similar numbers of new cases (1.62% v 1.64%, difference 0.02%, 0.5% to 0.5%). Conclusion: Active screening significantly increases detection. The preferred method of screening in 1 0 care is opportunistic pulse taking with follow-up ECG

13 NICE Guideline for AF (June 2014) Anticoagulation may be with apixaban, dabigatran, rivaroxaban or a vitamin K antagonist Discuss the options for anticoagulation with each patient and base the choice on their clinical features and preferences If anticoagulation is not tolerated or contraindicated consider left atrial appendage occlusion (LAAO)

14 Limitations of warfarin Narrow therapeutic window Wide variation in metabolism Numerous food and drug interactions Need for regular coagulation monitoring and dose adjustment Slow onset/offset Significant increase in intracranial and other haemorrhage Warfarin has a narrow therapeutic window Based on Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med. 1994;120:

15 Limitations of warfarin Narrow therapeutic window Wide variation in metabolism Numerous food and drug interactions Need for regular coagulation monitoring and dose adjustment Slow onset/offset Significant increase in intracranial and other haemorrhage Rivaroxaban Apixaban Apixaban Edoxaban Dabigatran Vit K sensitive: VII, IX, X & PT

16 Pivotal Warfarin Controlled Trials Stroke Prevention in AF Warfarin vs. Placebo 2,900 Patients NOACs vs. Warfarin 71,683 Patients 6 Trials of Warfarin vs. Placebo ROCKET AF (Rivaroxaban) 2010 ENGAGE AF-TIMI 48 (Edoxaban) 2013 RE-LY (Dabigatran) 2009 ARISTOTLE (Apixaban) 2011 Meta-analysis of large NOAC trials shows favourable risk/benefit ratio over warfarin Ruff et al., The Lancet 2013

17 All NOACS: Stroke or Systemic Embolism Risk Ratio (95% CI) RE-LY [Dabigatran 150 mg] 0.66 ( ) ROCKET AF [Rivaroxaban] 0.88 ( ) ARISTOTLE [Apixaban] 0.80 ( ) ENGAGE AF-TIMI 48 [Edoxaban 60 mg] 0.88 ( ) Combined n=58,541 Heterogeneity p= ( ) p=< Favours NOAC Favours Warfarin Meta-analysis of large NOAC trials shows favourable risk/benefit ratio over warfarin, Ruff et al., The Lancet 2013 Secondary Efficacy Outcomes Risk Ratio (95% CI) Ischemic Stroke 0.92 ( ) p=0.10 Hemorrhagic Stroke 0.49 ( ) p< Myocardial Infarction 0.97 ( ) p=0.77 All-Cause Mortality 0.90 ( ) p= Favours NOAC Favours Warfarin Ruff CT, et al. Lancet 2013

18 All NOACS: Major Bleeding RE-LY [Dabigatran 150 mg] Risk Ratio (95% CI) 0.94 ( ) ROCKET AF [Rivaroxaban] 1.03 ( ) ARISTOTLE [Apixaban] 0.71 ( ) ENGAGE AF-TIMI 48 [Edoxaban 60 mg] 0.80 ( ) Combined 0.86 ( ) p= Favours NOAC 1 2 Favours Warfarin Ruff CT, et al. Lancet 2013 Secondary Safety Outcomes Risk Ratio (95% CI) Intracranial Haemorrhage 0.48 ( ) p< GI Bleeding 1.25 ( ) p=0.043 Heterogeneity ICH, p=0.22 GI Bleeding, p= Favours NOAC Favours Warfarin Ruff CT, et al. Lancet 2013

19 GI Bleeding Rate (%) Number of Patients ARR in GI Bleeding (% per year) NOACs vs. Warfarin: Gastrointestinal Bleeding 5 ROCKET AF ARISTOTLE RE-LY Mean CHADS 2 = Mean CHADS 2 = 2.1 Mean CHADS 2 = P < P < * * Rivaroxaban Warfarin 0 Apixaban Warfarin 0 D110 mg D150mg Warfarin Patel et al. NEJM 2011;365(10):883-91; Connolly et al. NEJM 2009;361(12): ; Granger et al. NEJM 2011;365: GI Bleeding with Rivaroxaban is Less Severe than with Warfarin 4 Frequency of GI bleeding higher with rivaroxaban 5 Frequency of Fatal GI bleeding higher with warfarin 3.6% 2.6% With rivaroxaban With warfarin 0 With rivaroxaban With warfarin Sub-analysis of ROCKET-AF Presented during CHEST 2012, the annual meeting of the American College of Chest Physicians, held October , in Atlanta, Georgia

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21 egfr vs CrCl How we should measure renal fct BNF: for most drugs egfr is an adequate estimate but for low therapeutic index and high risk drugs, should use Cockcroft & Gault equation (ecrcl-cg) Serum creatinine is derived from muscle mass so the weight element of the equation should be an indication of muscle mass, not excess fat. BNF also states that the weight component of the equation be ideal body weight particularly important in obese patients

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23 Case Study Which anticoagulant? Apixaban 5mg bd Reduce dose to 2.5mg bd if 2 of:» > 80 years» Creat > 133 µmol/l» Weight < 60 kg or in severe renal impairment (creatinine clearance ml/min) Dabigatran 150mg bd (Dosette box not an option) Reduce dose to 110mg bd if any of:» > 80 years» HAS-BLED 3» Cr-Cl 30-49ml/min Edoxoban 60mg od Reduce dose to 30mg od if 2 of:» Weight < 60 Kg» Cr-Cl 15-49ml/min» Weight < 60 kg Rivaroxaban 20mg od Reduce dose to 15mg od if 2 of:» Cr-Cl 15-49ml/min The right dose for the right patient Dabigatran 1-3 Rivaroxaban 4,5 Apixaban 6,7 Edoxaban 8 Mode of action Thrombin Factor Xa Factor Xa Factor Xa Half life hrs 7-11 hrs 12 hrs hrs Dosing (in atrial fibrillation) B.D. O.D. B.D. O.D. Excretion 85% Renal 1/3 Renal 2/3 Hepatic 1/4 Renal 3/4 Non Renal 1/2 Renal 1/2 Non Renal Form Capsule Tablet Tablet Tablet Dose 150 mg 110 mg (>80 yrs, verapamil or increased bleeding risk) Cannot be put in dosette box 20 mg 15 mg (CrCl ml/min) 5 mg 2.5 mg (2 or more: >80yr; weight <60 kg; Cr >133mmol/L) or with severe renal impairment (creatinine clearance ml/min) 60 mg 30mg (1 of: <60Kg; CrCl 15-49ml/min; P-gp inhibitors) B.D. = twice daily; O.D. = once daily 1. Ezekowitz MD et al. Am Heart J 2009;157:805 10; 2.Connolly SJ et al. N Engl J Med 2009;361: ; 3. Connolly SJ et al. N Engl J Med 2010;363: ; 4. Rocket Investigators. Am Heart J 2010;159: ; 5. Patel MR et al. NEJM 2011;365:883 91; 6. Lopes et al. Am Heart J 2010;159:331-9; 7. Granger et al. N Eng J Med 2011;365: ; 8. Edoxaban SmPC July 2015

24 Case Study Monitoring Check FBC and LFTs initially and annually Reinforce importance of compliance!!!! Patient information leaflet and alert card Check renal function 6 monthly Rate and/or rhythm control.

25 NICE Guideline for AF (June 2014) Rate control should be initial 1 st line strategy for most AF patients unless: AF with reversible cause New onset AF (esp if < 65) HF thought to be primarily caused by AF Clinical judgement suggests rhythm control may be more suitable If drug Rx has failed to control symptoms: Ablation should be: offered to patients with paroxysmal AF considered for patients with persistent AF Rhythm control requires anticoagulation for 3 weeks prior to cardioversion unless AF onset < 48hrs Subsequent anticoagulation is dependent on stroke risk regardless of perceived effectiveness of rhythm control Rate control Strategy [Digoxin should only be considered as monotherapy in sedentary patients] First Line monotherapy: Beta Blocker or Rate-limiting CCB Atenolol, bisoprolol Diltiazem, verapamil Aim for ventricular rate bpm at rest

26 AF rate control during exercise Journal of the American College of Cardiology Volume 33, Issue 2, February 1999, Pages European Heart Journal Digoxin-associated mortality: a systematic review and meta-analysis of the literature Mate Vamos, Julia W. Erath, Stefan H. Hohnloser DOI: First published online: 4 May 2015 The present systematic review and meta-analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk, particularly among patients suffering from AF, (as well as HF)

27 Role of Echocardiography NICE - Echocardiography should be performed in: Younger patients when a baseline echo would be useful to guide long term management Patients considered for a rhythm control strategy Those patients where structural heart disease is suspected eg heart failure or heart murmur Those patients where the need for anticoagulation is not clear cut and further refinement of risk is needed Rule of thumb: An echo is unlikely to influence management if: Patient is > 75 and asymptomatic and no suspected heart failure or valve disease AF case detection..

28 Patients with AF (millions) AF: The Ticking Time Bomb The burden of AF will rise very sharply 13% in the last two decades 1 Estimated to at least double in the next 50 years Projected number of adults with AF in the United States by Year Mayo Clinic data (assuming a continued increase in AF incidence) 1 Mayo Clinic data (assuming no further increase in AF incidence) 1 ATRIA* study data 2 1. Miyasaka et al. Circulation 2006;114: Go et al. JAMA 2001;285: Adapted from Savelieva et al. Clin Cardiol 2008;31: *ATRIA = AnTicoagulation and Risk factors In Atrial fibrillation

29 Who else should we be screening? Hypertension Structural heart disease (eg heart failure, mitral valve disease) Obstructive sleep apnoea Use of technology: Portable ECG and leadless patch devices