DabigatranDr Ihab Suliman

2013

The New Oral Anticoagulants:Similar Yet Different

Thrombin Inhibitors:1. Dabigatran: pro-drug, renal clearance - twice daily

FXa Inhibitors:1. Rivaroxaban: renal clearance - once daily2. Apixaban: hepatic clearance - twice daily3. Edoxaban: hepatic clearance - once daily

Circulation 2010;121:1523-1532

Dabigatran: FDA Status

Pradaxa trade name

For the prevention of DVT/PE after orthopedic surgery:Pradaxa approved in EU and Canada

For the prevention of stroke in patients with non-valvular atrial fibrillation (SPAF):Pradaxa 150 mg BID FDA approved (Oct. 2010)

Pradaxa approved in EU, Canada and Japan

Dabigatran: FDA Approved Dosing

150 mg BID for SPAF 150 mg for CrCl >30 mL / min

75 mg for CrCl 15-30 mL / min

Stroke from Atrial Fibrillation

AF is the most preventable cause of stroke:12-16 million will be on warfarin treatment by

2050 in the USClinical trials have shown stroke can be

reduced:Placebo vs ASA = 19% ASA vs warfarin = 30% Placebo vs warfarin = 62% Dabigatran vs warfarin = 34%

Dabigatran: Not Without Issues1. No anticoagulant effect if missed dose

• 2% discontinuation rate due to GI distress

• Cost of drug ($240/mo vs $4/mo for warfarin)

2. No test to assess anticoagulation

3. Difficult to modulate dose

4. Bleeding in the elderly and renal impaired patients (5 dabigatran related deaths in Japan)

5. ‘Real world’ untested populations

6. Drug interactions

7. Limited data on bridging between anticoagulants

8. No specific antidote

9. 0.2% increase in myocardial infarction

10. Off-label use

Dabigatran: Laboratory Testing

Monitoring vs anticoagulant assessment PT and aPTT

Differing reagent sensitivities

Not a linear association between assay values and drug level

Not validated for association to bleeding

aPTT may be applicable for qualitative assessment

INR: not sensitive; not validated

TT: Super-sensitive; can identify if any drug onboard

Ecarin clotting time: results can vary depending on plasma factors; research use only (RUO)

PiCT: RUO

Chromogenic anti-FIIa

Hemoclot: quantitative using dabigatran calibrators; FDA approved yet?