The New Oral Anticoagulants:Similar Yet Different Thrombin Inhibitors: 1. Dabigatran: pro-drug, renal clearance - twice daily FXa Inhibitors: 1. Rivaroxaban: renal clearance - once daily 2. Apixaban: hepatic clearance - twice daily 3. Edoxaban: hepatic clearance - once daily Circulation 2010;121:1523-1532
Dabigatran: FDA StatusPradaxa trade nameFor the prevention of DVT/PE after orthopedic surgery: Pradaxa approved in EU and CanadaFor 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 Dosing150 mg BID for SPAF 150 mg for CrCl >30 mL / min 75 mg for CrCl 15-30 mL / min
Stroke from Atrial FibrillationAF is the most preventable cause of stroke: 12-16 million will be on warfarin treatment by 2050 in the US Clinical 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 Issues 1. 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?