42
Dr Joe Martins, Consultant Cardiologist Russells Hall Hospital
Dr Joe Martins, Consultant Cardiologist
Russells Hall Hospital
What am I going to cover……
• Some basic clinical knowledge on AF
• How we implemented the NOACs in Dudley
AF is not benign
Average stroke rate = 5%/yr (0-12%) ◦ If include TIA / ‘silent strokes’ = 7% / yr
Stroke risk is highest in the first few months after diagnosis – early risk stratification and oral anti-coagulation (OAC) is vital
Strokes due to AF have higher mortality and greater residual disability
Diagnosing AF before complications occur is a recognised priority for stroke prevention – opportunistic pulse check for all >65s - perform ECG if irregular
Many patients remain undiagnosed and untreated. Despite the wealth of evidence for warfarin only ≈ half receive warfarin
All cause mortality, strokes and intracranial bleeds are all reduced by OAC irrespective of bleeding risk
Swedish AF Cohort Study, AFriberg L et al. Circulation. 2012;125:2298-2307
High bleeding risk
Low bleeding risk
HR 0.26-0.72
So why is anticoagulation under-prescribed???
Physician Factors: Fear of bleeding - the Hypocratic Oath?! Fear that RCTs not reflective of true clinical practice Lack of experience and knowledge
Patient Factors: Inconvenience of frequent INR monitoring Fear of bleeding Inadequate counselling Work/travel problems
1) Identify and diagnose patients with AF
2) Risk stratify
3) Anticoagulate high risk patients
C – CHF - 1 H – HT - 1 A – age ≥75 - 1 D – Diabetes - 1 S2 – Stroke/TIA - 2
Consistently places more patients into low or
moderate risk compared to other risk stratification schemes
Potential for underutilisation of OAC BUT IT’S WHAT QOF USES
9
Low Risk (score 0)
Intermediate Risk (score 1)
High Risk (score ≥2)
CHADS2, 1 year 1.67 4.75 12.27
CHA2DS2-VASc, 1 year
0.78 2.01 8.82
Olesen JB, Lip GYH, Hansen ML, et al. BMJ 2011
973 patients with AF > 75 years
260 GP practices
Mean age = 81.5yrs
Follow up – 2.7 years
Mant JW et al. Lancet 2007; 370:493-503, 460-461.
Mant JW et al. Lancet 2007; 370:493-503, 460-461.
End point Warfarin Aspirin Hazard ratio (95% CI)
NNT
Fatal or nonfatal disabling stroke or significant arterial embolism (%/annum)
1.8
3.8
0.48 (0.28–0.80)
50
Mant JW et al. Lancet 2007; 370:493-503, 460-461.
End point Warfarin Aspirin Hazard ratio (95% CI)
Major extracranial hemorrhage (%/annum)
1.4
1.6
0.87 (0.43–1.73)
All major hemorrhages (%/annum)
1.9
2.2
0.96 (0.53–1.75)
ESC 2012 Updated AF Guidelines:
“The evidence for effective stroke prevention with aspirin in AF is weak, with a potential for harm, as data indicate that the risk of major bleeding or intracranial haemorrhage is not significantly different to that of OAC, especially in the Elderly.”
“Given the availability of NOACs, the use of antiplatelet therapy for stroke prevention in AF should be limited to the few patients who refuse any form of OAC.”
Active bleeding
Previous allergic reaction -rare
Non-compliance (consider dementia in context)
◦ Previous intracerebral bleed
◦ (Alcohol dependence / abuse)
◦ (Frequent falls)
◦ (Severe liver disease)
◦ (Active malignancy)
The problem with warfarin
Drug interactions with warfarin – decreased effect
Amobarbital Butabarbital Carbamazepine Cholestyramine Dicloxacillin Griseofulvin Mercaptopurine Mesalamine Nafcillin Phenobarbital Phenytoin
Primidone Ribavirin
Rifabutin Rifampin Secobarbital Sucralfate Vitamin K
Coenzyme Q10 Ginseng St. John’s wort Green tea
Drug interactions with warfarin – increased effect Acetaminophen
Alcohol (binge) Allopurinol Amiodarone Argatroban Aspirin Azithromycin Bactrim Chloral hydrate Chloramphenicol Cimetidine Ciprofloxacin Citalopram
Clarithromycin Clofibrate Danazol Diltiazem Disopyramide
Disulfiram Doxycycline Entacapone Erythromycin Felbamate Fenofibrate Fluconazole Fluorouracil
Drug interactions with warfarin – increased effect Gemfibrozil
Influenza vaccine Isoniazid Itraconazole Levofloxacin Metronidazole Miconazole Moxalactam Neomycin Norfloxacin Ofloxacin Omeprazole Phenylbutazone
Piroxicam Propafenone Propranolol Quinidine Ritonavir Sertraline Simvastatin Sulfamethoxazole Sulfinpyrazone Tamoxifen Testosterone Tetracycline Vitamin E
Drug interactions with warfarin – increased effect Voriconazole
Zafirlukast Anise Asafoetida Chamomile Clove Danshen Devil’s claw Dong quai Fenugreek Feverfew Fish oil Garlic Ginger
Ginkgo Grapefruit Horse chestnut Licorice root Mango Meadowsweet Onion Papain Quassia Red clover Rue Sweet clover Tumeric Willow bark
And it’s no good if you like your green leaves and vegetables
Or if you like a drink on the weekend....
Or if you don’t like needles (or doctors and nurses!)...
Extensive food and drug interactions
Slow onset, long half life
Inter and intra-patient variability
Narrow therapeutic window
Frequent life-long monitoring
Impact on people’s work, social and family life
More litigation surrounds warfarin than any other medication!
Would warfarin even be licensed today
The Novel Oral AntiCoagulants (NOACs)
(a more intelligent rat killer)
◦ Dabigatran - Pradaxa ◦ RELY, NEJM 2009
◦ Rivaroxaban - Xarelto ◦ ROCKET-AF, NEJM 2011
◦ Apixaban - Eliquis ◦ ARISTOTLE, NEJM 2011
◦ Edoxaban - Lixiana ◦ ENGAGE-AF, NEJM 2013
The NOACs or Oral Direct Inhibitors (ODI)
At least as effective as warfarin at preventing stroke in AF
Less intracranial bleeding
Less cumbersome – interactions/monitoring
More predictable
Faster onset / shorter half-life
Can be placed in dossette boxes
Relatively limited clinical experience
Costly (+/- £800/yr compared with £280/yr with warfarin)
Hepatic / renal dose adjustment (contra-indicated if eGFR<30ml/min)
No antidotes (yet)
No obvious lab monitoring marker
Some twice a day drugs - ? compliance
In RE-LY, patients with a history of heart valve disorder (i.e., prosthetic valve or hemodynamically relevant valve disease)
In ROCKET, patients with hemodynamically significant mitral valve stenosis or prosthetic heart valve (annuloplasty with or without prosthetic ring, commissurotomy and/or valvuloplasty were permitted)
In ARISTOTLE, patients with clinically significant (moderate or severe) mitral stenosis, or prosthetic mechanical heart valve.
What exactly is non-valvular AF?
Hx of valve replacement – mechanical or bioprosthetic
Hx of rheumatic valve disease – especially mitral stenosis
(known severe valvular regurgitation/stenosis)
So NOACs contra-indicated if..
“The NOACs so far tested in clinical trials have all shown noninferiority compared with VKAs, with better safety, consistently limiting the number of ICH.”
“On this basis, this guideline now recommends them as broadly preferable to VKA in the vast majority of patients with non-valvular AF.”
“In the absence of head-to-head trials, it is inappropriate to be definitive on which of the NOACs is best, given the heterogeneity of the different trials.”
No primary care anticoagulation service in Dudley 2011/12 - horizon scanning
December 2011 - initial discussions on managed entry of NOACs before the NICE TAs June 2012 - agreed plan for Dabigatran and Rivaroxaban November 2012 – NOACs entered routine
clinical practice
How we did it in Dudley
CCG reported 6120 patients on AF register, 607 with CHADS2 >1 and not receiving appropriate anticoagulation. 2936 cases were exception reported. 2013/14 CCG Locally Agreed Quality Premium-included AF 2013- established Health Economy Anticoagulation Steering Group
How we did it in Dudley
Case finding- GRASP AF tool run in every GP Practice, CHA2DS2-VASc scoring applied
March 2014- 928 patient reviews completed by Practice Based Pharmacists and GPs Results: AF register increased by 286 patients (5.21%, prevalence from 1.92% to 2.02%) 130 patients commenced on anticoagulation 43 (33%) warfarin 87 (67%) on NOACs
GP Briefing produced: www.dudleyformulary.nhs.uk
How we did it in Dudley
37
GP Education sessions delivered by multidisciplinary team Review of Commissioning pathway for anticoagulation services commenced Anticoagulation declaration signed by nominated GP anticoagulation lead for each GP Practice
How we did it in Dudley
Identify patients with new AF – ECG diagnosis Use new CHA2DS2-VASc to risk stratify
If CHADS-VaSc =0 (<65 with lone AF, incl women) –
no anticoagulation
Check the HAS-BLED score – if high, don’t stop yourself from prescribing OAC – see if you can modify risk
If CHA2DS2-VASc score ≥1 men and ≥ 2 in women, ANTICOAGULATE
I recommend WARFARIN if: 1. Valvular AF (Rheumatic, prosthetic, severe) 2. Significant renal impairment (GFR <30) 3. Compliance concerns
If none of the above, then I offer an informed choice of warfarin versus NOAC
Aspirin only - NO
NOACs will be the standard of care for the majority of patients with AF
What does the future hold?
