1. Net clinical benefit of OAC
Net clinical benefit - stroke, systemic embolism, ICH – events prevented per 100 person years
Singer 2009

2. All cause mortality benefit OAC
Hart 2007 metanalysis 11 RCT’s:
Mean age 69 yrs
Mortality reduction of 26% (95% CI 3%-43%)
Go et al 2003 (ATRIA cohort) – ‘real world’:
11,526 patients, mean age 71yrs
Approx 40% > 75yrs, 10% > 85 yrs
Mortality reduction 31% (95% CI 23% - 39%)

3. Risk – treatment paradox
AF – highest prevalence in the elderly
Elderly – highest risk of stroke
Elderly – most likely to benefit from OAC
Elderly – least likely to receive OAC
White 1999

4. Risk – treatment paradox
Under-use of OAC in AF:
US, Italy, Canada, Germany: % eligible
In relation to age:
Canada, Japan: 70% in patients < 75 yrs
30% in patients > 75yrs
UK 2013:
55-70% in patients < 75 (1/3 eligible total)
40-55% in patients > 75 (2/3 eligible total)
Stafford 1998, Ageno 2001, CQIN 1998, Geisler 2001
Partington 2007, Furosho 2008
Mohammed 2013

5. Quality of INR control
Efficacy of warfarin limited by quality of INR control (time in therapeutic range – TTR):
Multiple food and drug interactions
Variable pharmacodynamics
Narrow therapeutic window (INR 2-3)
Need for regular monitoring and dose adjustment

6. Quality of INR control
Connolly 2008

7. Novel oral anticoagulants
Direct thrombin inhibitor:
Dabigatran etixilate
Factor Xa inhibitors:
Rivaroxaban
Apixaban
Edoxaban
Quick onset of action
Short half life and offset
No monitoring
Steady plasma concentration
Less food and drug interactions

8. Efficacy vs safety NOACs
Ruff 2013

9. ESC guidelines 2012 No antithrombotic therapy (or aspirin)
Oral anticoagulant (or aspirin)
Oral anticoagulant
(VKA or NOAC)

10. Assessment of bleeding risk
HASBLED score:
Score:
0 = 1%
1 = 1%
2 = %
3 = %
>4 = > 8%
Score 3 or more – caution and careful monitoring with OAC/aspirin
NOT CONTRAINDICATION
BP >160 systolic
Dialysis or Cr > 200
LFT – bil x2, ALT/AST x 3
Labile INR (TTR<60%)
NSAIDS, antiplatelets
Pisters 2011

11. How not to use HASBLED Case study:
74 yr old gentleman
Right sided acute stroke
Known AF
RA – on NSAIDS
BP ranges mmHg systolic
CHADSVASC = 4 (4% annual stroke risk)
HASBLED = 4 (8.7% annual bleeding risk)
Bleeding > stroke risk – therefore not OAC
!!!!

12. Falls Commonly sited reason not to use OAC or stop treatment.
Gage 2005:
- Retrospective cohort ~ 20,000 patients AF.
- Falls associated with 3 x risk ICH:
- Warfarin not associated with increased risk of ICH in
patients who fall:
- Warfarin treatment associated with significantly reduced composite of
death, hospitalisation for stroke, MI, ICH (~25%).
Donze 2012:
- Prospective analysis of > 500 high risk fallers with AF.
- No increased risk of ICH with warfarin.

13. Combination anti-thrombotics
Hansen 2010:
Follow up study of >82,000 patients hospitalised for AF.

14. Cognitive impairment Shireman 2004: Flaker 2010:
Retrospective analysis of >10,000 elderly US patients with AF.
Dementia associated with trend suggesting more bleeding events, but didn’t reach significance – HR 1.56 (95% CI )
Flaker 2010:
Post-hoc ACTIVE-W.
2,500 had MMSE.
7% dementia.
MMSE score correlated to TTR.
TTR
MMSE
Engineer ways to optimise compliance

15. Frailty
Poli 2011:
Prospective study of > 3,000 elderly AF patients naïve to OAC.
Average age 84 yrs (range 80 – 102).
TTR 62%
Major bleeding rate 1.9% per year.
Perera 2009:
Prospective evaluation of 220 frail patients.
Frailty associated with poor outcome compared to non-frail irrespective of anti-thrombotic used.
Frail seem to be at higher risk of stroke than bleeding compared to non-frail.

16. Patient counselling Explain how AF increases stroke risk
Discuss stroke risk (CHADS-VASC) –
more than likely lose of independence if this occurs.
Explain risk of ICH – LOW – (<1%)
Explain risk of extracranial bleeding (aspirin = OAC)
Unlikely to lose independence if this occurs
Informed patient decision

17. Warfarin & NOACs PATIENT CHOICE Well controlled INR Labile INR
CKD / CrCl < 30
Requires good renal function
GI bleed
High risk ICH
Prosthetic heart valve
Difficulty with INR monitoring or dose adjustment
Rheumatic heart disease
PATIENT CHOICE

18. Summary
AF is extremely common, and will increase with our aging population.
Stroke related to AF is often devastating with high human and economic implications.
Anticoagulation is superior to aspirin or no anti-thrombotic therapy in terms of overall benefit / mortality in patients with AF.
This net clinical benefit increases with age, however observed rates of anticoagulation use are lowest in the elderly.
Anticoagulation decisions in the frail can be very difficult.

19. Summary There are still a large number of strokes we can avoid.
The default position for elderly patients (>75 yrs) with AF should be that they are offered OAC unless there is a good reason not to.
Bleeding risk tools (e.g. HASBLED) should be use to optimise patient related factors, rather than rule OAC out.
NOACs offer an alternative to warfarin that may improve overall use and efficacy of anticoagulation for AF.
There are still a large number of strokes we can avoid.

20. Thanks for listening!