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New Approaches in the Management of Atrial Fibrillation

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Ajay Dharod

on 10 December 2013

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Transcript of New Approaches in the Management of Atrial Fibrillation

New Approaches in the Management of Atrial Fibrillation
Ajay Dharod
1 Epidemiology
2 Guidelines
Lily Loves Cheese!
And Cheese Its.
And Cheese Puffs.
And sometimes Cashews.
Strict rate control is NOT ALWAYS necessary.
Anticoagulation is always on the algorithm.
Guidelines for Preventing Thromboembolism
Stroke Risk or Bleeding Risk?
From funnyjunk.com
We are going to anti-coagulate intermediate and high-risk patients because there is a proven benefit. So how do we more accurately identify truly LOW-RISK patients?

But I don't want to cause unnecessary bleeding complications by anti-coagulating more patients... is there a way to predict how likely they are to have a bleeding complication?
1) In patients with CHADS2 Scores of 0 or 1, identify your truly LOW RISK PATIENTS via CHA2DS2-VASc. Everyone else should be considered for anti-coagulant therapy.
2) Use HAS-BLED to 'flag' patients at risk for bleeding complications.
Targets (DTI vs. Xa)
5 Monitoring & Reversal Agents
6 Pharmacogenomics
Chicken, Crackers, Dog Treats & Doritos
French Fry, Hamburger, Hashbrown
Indian Snacks, Lettuce, & a Lifesaver
3 Risk Stratification
Metanalysis of RE-LY, ROCKET-AF, ARISTOTLE versus Warfarin
Will the NOACs be the Statins of Anticoagulation?
All cause stroke and systemic embolism
Ischemic and unspecified stroke
Hemorrhagic stroke
Major Bleeding
Intracranial Bleeding
Gastrointestinal Bleeding
Dabigatran (Pradaxa)
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Lixiana)
?more practical?
?less bias?
sample size difference
genotyping assay
Mac & Cheese, Marsh-mellow, Pepperoni, Pita Bread
Age is the most important co-variate to estimate risk of bleeding in multiple studies... it's only given 1 point here...
Camm J et al 2012, ESC Guidelines.
"The NOACs so far tested in clinical trials have all shown non-inferiority 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
" Aspirin is no longer in guidelines.

You JJ et al. CHEST 2012. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
Favors dabigatran over warfarin.

To begin with... we need to be able to measure Thrombin or Factor Xa activity in addition to measurement of plasma drug levels.
Pro-thrombin complex concentrate (PCC)
- 3 Factor PCC contains factors II, IX and X
- 4 Factor PCC adds factor VII
- Fractionated from human plasma (30,000) donations
- Virally inactivated by 2 different methods
- Can be administered in minutes
- Risks: Thrombosis, (infections, allergic reactions).

There is also an activated version with activated clotting factors (FEIBA) but there is more risk of thrombosis and there is no safety data in NOACs.
Non-PCC based future reversal agents
For Dabigatran
- humanized monoclonal antibody fragment
- developed by Boehringer Ingelheim
- FAB: rapid affinity binding to Dabigatran
- Dose dependent reversal in animal models
For Rivaroxaban
- r-Antidote developed by Portola
- Truncated inactive Xa that binds Xa inhibitors (competitive)
- Effective reversal in animal models
Dabigatran's relatively low plasma protein binding (35%) implies that it may be dialyzed.

Animal models have demonstrated the efficacy of dialysis.

One study including patients on hemodialysis receiving a single dose of dabigatran, 62% of the drug was removed after 2 h and 68% after 4 h of dialysis.

Several case reports have indicated the successful and safe use of hemodialysis for the removal of dabigatran.

This method is however limited by the
difficulty of inserting central dialysis catheters in a patient who is fully or excessively anticoagulated,
inducing the risk of additional bleeding.
PER977 is a synthetic small molecule developed by Perosphere Inc and it has been demonstrated to
bind to several NOACs, including dabigatran, rivaroxaban, apixaban and edoxaban.

?A potential universal antidote?
Current guidelines recommend PCC
Good (Short) Review Article
Pizza Crust, Skittle, Taco Shell, Tater Tot
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