AGS 2012 Friday: New Anticoagulation Strategies in AF

Simpler but Safe? New Oral Anticoagulant Therapies Versus Warfarin to Reduce Stroke Risk in Older Atrial Fibrillation Patients

Atrial fibrillation markedly increases in incidence, prevalence and associated poor outcomes with advancing age. This case-based symposium revisits the risks and benefits of chronic anticoagulation in older adults with non-valvular atrial fibrillation, including new oral therapies (direct thrombin and factor Xa inhibitors) which do not require monitoring. The objectives of this symposium are
1) to emphasize the age-specific stroke vs. bleeding risk in chronic non-valvular atrial fibrillation patients
2) to reveal misconceptions on anticoagulation risk in older patients and introduce strategies to reduce poor outcomes in this cohort
3) to review the evidence and age-specific use of warfarin in chronic afib and
4) to review efficacy and safety data for new oral anticoagulation therapies including dabigatran, rivaroxaban and apixaban in seniors.

Mantras and Myths: Clarifying the Challenges of Anticoagulation in Older Adults with Chronic Atrial Fibrillation
Michael Chen, MD, FACC, University of Washington .
Take Home Points 
 Age is a potent RF for stroke w/ and w/o afib
 Anticoagulation is under-prescribed
- Underestimation of benefits
- Overestimation of risks
 Anti-thromboembolic strategies need to be individualized after a frank discussion with patients
 Decisions are not final

Slide 20
- A Markov decision model demonstrated that, regardless of age or baseline risk of stroke, the risk of falling was not an important factor for determining the optimal antithrombotic therapy (i.e., aspirin, warfarin or no therapy)
- Risk of SDH from falling is so small that patients with Afib with an average risk of stroke (6% per year in the absence of anticoagulation) would have to fall nearly 300 times in a year for the risk of anticoagulation to outweigh its benefits

Warfarin in Seniors: When and How
Gregory Piazza, MD, Brigham and Women's Hospital 
Take-Home Points• Stroke prevention strategies in senior patients with AF should begin with an assessment of stroke and bleeding risk.
• Although effective for stroke prevention in AF, warfarin has particular limitations that are especially important in the senior population, including drug-drug interactions and the need for dose adjustment and monitoring.
• Anticoagulation Management Services and home INR testing have the potential to improve the safety and efficacy of warfarin for stroke prevention in seniors.

Slide 6
- The rate of ischemic stroke among patients with AF included in primary prevention trials and not treated with antithrombotic therapy averages 4.5% per year
- AF increases the risk of stroke 4- to 5-fold, across all age groups.
Slide 11
- Stroke prevention guidelines based on CHADS2 score
Slide 12
- CHA2DS2VAS index: may be more helpful in stratifying low risk pts for warfarin 
Slide 13
- HAS-BLED score can be used to determine bleeding risk
Slide 22
- current guidelines recommend using ASA+Plavix in pts with C/I to warfarin
Slide 26
- average bleeding risk on warfarin = 1.2%/y

Dabigatran, Rivaroxaban, Apixaban: Better than Warfarin in Older Afib Patients?
Susan Cheng, MD, Brigham and Women's Hospital
Summary
• New oral anticoagulants have arrived, and stroke prevention in AF is as good or better than warfarin
• Newer drugs are better for ICH, worse for GI bleed
• Know your patient’s risk for embolism vs bleed
• Warfarin works with stable INRs
• For newer drugs, dose carefully based on correct CrCl
• Cost will be an issue for many
• In the absence of assays, monitor clinically
• We need more data in older adults
Slide 13
- Dabigatran (RELY study) 150 mg BID vs. warfarin
PROS:
1. less ischemic stroke
2. less hemorrhagic stroke & intracranial bleed
CON:
1. bid dosing
2. more major GIB
Slide 18
- Rivaroxaban (ROCKET-AF) vs. wafarin
PROS:
1. less hemorrhagic stroke & intracranial bleed
CONS:
1. more major GIB
Slide 21
- Apixaban (ARISTOTLE) vs. warfarin
PROS:
1. less ischemic stroke
2. less hemorrhagic stroke & intracranial bleed
3. less major bleed
4. subgp analysis suggest Apixaban may be more effective than warfarin in stroke & systemic embolism & less risk of major bleeding with increasing age gp
4. subgp analysis: less risk of major bleed with mod-severe renal impairment
Slide 26
What the Guidelines Are Saying
• European Society of Cardiology (2010)
– Oral anticoagulation focus still warfarin
– For HAS-BLED score 0-2, dabigatran 150 mg bid acceptable
– For HAS-BLED score ≥3, dabigatran 110 mg bid acceptable
• ACC / AHA (2011)
– Dabigatran an alternative to warfarin if no valve disease, CrCl<15, liver disease
• Canadian Society of Cardiology (2012)
– Recommending newer anticoagulants over warfarin
– Efficacy and safety similar for ≥ vs <75 yrs for rivaroxaban and apixaban
– Consider dose reduction of new anticoagulants in patients >75 yrs and definitely in patients >80 yrs, especially dabigatran
• ACP (2012)
– Recommending dabigatran 150 mg po bid over warfarin
Slide 35
One Approach
1. Does the patient need oral anticoagulation? (CHADSvasc)
2. What is the patient’s bleed risk? (HAS-BLED)
3. Is there a compelling indication for a newer anticoagulant?
• Patient refuses warfarin
• Patient has unstable INRs on warfarin
4. Are there contraindications to newer agents?
• Severe renal and/or liver disease, valve disease
5. If choosing warfarin, optimize time in therapeutic range
• Centers can have TTRs ranging from 40% to 70%
6. If choosing newer agent, carefully consider dosing issues
• Avoid high dose dabigatran in patients >75 to 80 yrs
• Screen for risk of GI bleed (ulcer, NSAIDs, etc.)