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This podcast is developed by the Pulmonary Embolism Response Team (PERT).  PERT Consortium was developed after the initial efforts of a team of physicians at Massachusetts General Hospital. The first PERT sought to coordinate and expedite the treatment of pulmonary embolus with a balanced team of physicians from a variety of specialties.  Listen here for the lastest in research and discussion on Pulmonary Embolism.

Dec 19, 2019

Episode 3: James Horowitz interviews Rachel Rosovsky on DOACs.

Dr. Rosovsky is the Director of Thrombosis Research in the Division of Hematology at Mass General Hospital. She is also an Assistant Professor at Harvard and a member of the Board of Directors of the PERT Consortium. 

Dr. Horowitz is the Director of the CCU at NYU Langone Health and the Co-Chair of the Interdisciplinary Resuscitation Committee. He is also an Assistant Professor or Medicine and a member of the Board of Directors of the PERT Consortium.

Directly acting oral anticoagulants.  

  • FDA approved DOACS: Xarelto (rivaroxaban), Eliquis (apixaban), Savasya (edoxaban), Pradaxa (dabigatran).

  • All DOACs have similar efficacy in terms of VTE occurrence and better safety profile compared compared to Coumadin.

MOA:

  • Dabigatran: directthrombin inhibitor.  
  • Rest of the DOACs: factor X inhibitors.
  • DOACS usually do not need monitoring. Most common interaction noted with drugs like ketoconazole (CYP3A4).

Dosing:

  • Dabigatran and Edoxaban: Overlap with parenteral enoxaparin for 5 to 10 days is needed.
  • Apixaban and Rivoraxaban: Need loading dose. For apixaban it is 10 mg 2 times a day for 7 days followed by 5 mg 2 times a day.  Rivaroxaban: 15 mg 2 times a day for 21 days followed by 20 mg once a day. (Xarelto need to be taken with food)
  • Only 55% of the patients with Coumadin remain in therapeutic range.

Drug reversal agents for DOACs

  • Dabigatran reversal: Idarucizumab
  • Xarelto and Eliquis reversal: Andexenat Alpha.

Factors in deciding candidacy for DOACs:

  • DOACs in patients with Child-Pugh score B/C cirrhosis should not be used.
  • Renal failure with CrCl <30: either low dose DOACs (i.e. edoxaban) or avoid DOACs.
  • No DOACs for weight >120 kg, based on ISTH guidelines. (higher the BMI may have increased risk of bleeding with better efficacy, potentially due to absorption issues-- levels can fluctuate)

Drug monitoring for DOACs:

  • No standardized methods. Not routinely done.
  • It should be considered in patients with extremes of weight and patients who have gone gastric/bariatric surgeries, because all DOACs are absorbed get into upper GI tract.

Pregnancy and Venous thromboembolism:

  • No DOACs in pregnancy.
  • Enoxaparin is the treatment of choice -1 mg/kg every 12 hours up to week 36 followed by changing them to unfractionated heparin. (subcutaneous calculated dose).
  • Patients who had prior DVTs/PEs and become pregnant may need prophylactic dose of enoxaparin (40 mg subcutaneous once a day)

Cancer and VTE:

  • VTE is a second leading cause of death in cancer patients.
  • Drug of choice was enoxaparin over warfarin.
  • Edoxaban Vs Enoxaparin: Edoxaban with less recurrent VTE, but worse bleeding profile (most bleeds in gastric cancer patients)
  • Rivaroxaban Vs Enoxaparin: Rivaroxaban with less recurrent VTE, but worse bleeding profile (most bleeds in gastric cancer)
  • Cancer patients who may not be good candidate: a) GI cancer b) needing many procedures c) liver/renal failure d)brain mets. 

Provoked vs Unprovoked and extended a/c:

  • Unprovoked PE: Two-year risk of recurrence 25% or higher.
  • Provoked by surgery [mainly orthopedic surgery, pregnancy, long hospital stay]: risk of recurrence 1% at one year, 3% at 5 years.
  • Flying is a weak risk factor to be considered as provoked.
  • Amplify-Ext trial: 70% decrease risk of recurrence with low dose apixaban without an increased risk of bleeding in unprovoked VTE.
  • Einstein Choice trial: 70% decrease risk of recurrence with low dose rivaroxaban without an increased risk of bleeding. 60% of patients had provoked VTE with ongoing risk factors. (i.e. Obese patients, patients who are immobile, and are still immobile).

Cancer screening following PE:

  • 5-10% of patients with VTE would be diagnosed with malignancy in next 5 years. Recommendation is to do age appropriate cancer screening.

Valves and DOACS:

  • (increase risk of ischemic events)

 

Reference:

Rali PGangemi A Moores A et al. Direct-Acting Oral Anticoagulants in Critically Ill Patients. Chest. 2019 Sep;156(3):604-618.