Download Net clinical benefit of OAC

Net clinical benefit of OAC
Net clinical benefit - stroke, systemic embolism, ICH – events
prevented per 100 person years
Singer 2009
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%)
Risk – treatment paradox
White 1999
Risk – treatment paradox
• Under-use of OAC in AF:
– US, Italy, Canada, Germany:
20-40% eligible
Stafford 1998, Ageno 2001, CQIN 1998, Geisler 2001
• In relation to age:
– Canada, Japan: 70% in patients < 75 yrs
30% in patients > 75yrs
Partington 2007, Furosho 2008
• UK 2013:
– 55-70% in patients < 75(1/3 eligible total)
– 40-55% in patients > 75(2/3 eligible total)
Mohammed 2013
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
Quality of INR control
Connolly 2008
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
Efficacy vs safety NOACs
Ruff 2013
ESC guidelines 2012
No antithrombotic
therapy (or aspirin)
Oral anticoagulant
(or aspirin)
Oral anticoagulant
(VKA or NOAC)
Assessment of bleeding risk
• HASBLED score:
•
Score:
–
–
–
–
–
BP >160 systolic
Dialysis or Cr > 200
LFT – bil x2, ALT/AST x 3
Labile INR (TTR<60%)
NSAIDS, antiplatelets
Pisters 2011
0
1
2
3
>4
=
=
=
=
=
1%
1%
1.8%
3.74%
> 8%
•
Score 3 or more – caution and
careful monitoring with
OAC/aspirin
•
NOT CONTRAINDICATION
How not to use HASBLED
• Case study:
–
–
–
–
–
74 yr old gentleman
Right sided acute stroke
Known AF
RA – on NSAIDS
BP ranges 160-170 mmHg systolic
• CHADSVASC = 4 (4% annual stroke risk)
• HASBLED = 4 (8.7% annual bleeding risk)
• Bleeding > stroke risk – therefore not OAC
!!!!
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.
Combination anti-thrombotics
• Hansen 2010:
– Follow up study of >82,000 patients hospitalised for AF.
Cognitive impairment
• Shireman 2004:
– 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 0.95-2.57)
–
–
–
–
Post-hoc ACTIVE-W.
2,500 had MMSE.
7% dementia.
MMSE score correlated to
TTR.
TTR
• Flaker 2010:
MMSE
Engineer ways to optimise compliance
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.
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
Warfarin & NOACs
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
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.
Summary
• 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.
Thanks for listening!