Advanced Issues in Peri-Operative VTE Prevention

Transcription

1 Advanced Issues in Peri-Operative VTE Prevention Michael-Anthony (M-A) Williams, M.D. Consultant Physician Centura Medical Consultants September 27th, 2012 Main Topics 1. The perils of the early mover- Dabigatran 2. The promise of the anti-factor Xa drugs: Rivaroxaban and Apixaban 3. When do we change from standard therapy? 2 Case Presentation #1 A 67 year old male with a history of hypertension and hyperlipidemia undergoes an elective total hip arthroplasty. What are acceptable choices for VTE prevention? A. Coumadin B. Rivaroxaban, 10mg po daily C. Enoxaparin, 30mg SQ BID D. Aspirin, 325mg po BID E. Dabigatran, 150mg po daily F. All of the above G. All except E 3

2 Why are we even looking for a new agent? 1. Enoxaparin- lots of people don t like to inject themselves, and it is still expensive. 2. Coumadin works, but often the therapeutic range is found only 50% of the time. 3. Aspirin.actually works better than you might think. 4 Total joints and VTE- a history Initial occurrence rate of VTE (PE/DVT) was thought to be 40-60%, but with advances in surgical technique and markedly reduced LOS, the accepted rate without prevention is 4.3% at 35 days. That drops to <2% with appropriate treatment, currently defined against the gold standard of Enoxaparin 30mg SQ BID. Mean time to DVT is 20 days for THA for 10 days for TKA, so most occur after discharge. 5 The most desirable outcome 1. As hospitalists, we are overwhelmingly concerned with acute VTE events and what I would term hemodynamically significant bleeding. 2. The surgeons are concerned with acute VTE events and surgical site bleeding- with the risk for infection or re-operation. 3. This leads to some difference of opinion. 6

3 ACCP (Chest) and AAOS 1. ACCP published VTE guidelines for 20 yrs. 2. AAOS in 2008 published guidelines for the first time, and focused on PE, did not include DVT as an outcome for studies. 3. AAOS updated guidelines in 2011 suggesting the use of VTE prophylaxis, but making no recs for agent or length of rx. 4. ACCP 2012: Any agent, they prefer LMWH, recommending days of treatment. 7 Case Presentation #2 Which of the following are associated with an increase risk of bleeding with Dabigatran (Pradaxa)? A. B. C. D. E. Renal dysfunction Elderly age Low BMI Verapamil/Amiodarone All of the above 8 Dabigatran (Pradaxa) 1. Direct thrombin inhibitor 2. Studied in the RE-MOBILIZE/RE-NOVATE/ RE-MODEL trials at 150mg or 220mg daily. 3. Study results show comparable effect to LMWH. 4. So far, only approved in US for Afib, but there is a trend to off-label use here. 9

4 Dabigatran (Pradaxa) 1. Not yet approved for VTE prevention- only for Afib. 2. Main side effect is GERD. 3. Lots of off label use has led to multiple reports of bleeding, specifically in the elderly, with renal dysfunction, and low BMI. 4. More reported ADEs in 2011 than any other drug- 4x as many as coumadin, mainly due to bleeding. 5. No known reversal agent. 10 Case Presentation #3 An 80 year old female can t wait to get her new knee but she doesn t want to have those blood thinner shots. Her options for VTE prevention include all of the following except: A. Apixaban (Eliquis) B. Coumadin C. Aspirin D. Rivaroxaban (Xarelto) 11 Rivaroxaban (Xarelto) & Apixaban (Eliquis) 1. Anti-Factor Xa inhibitors 2. RECORD trials for Rivaroxaban 10mg po daily show it to be superior to Enoxaparin, but with a higher incidence of bleeding. Approved for VTE prevention in US/Europe 3. ADVANCE trials for Apixaban 2.5mg po bid: Superior to Enoxaparin with a lower bleeding risk. Approved only in Europe for VTE prevention. 12

5 Rivaroxaban (Xarelto) & Apixaban (Eliquis) 1. Potential pitfalls: A. Rivaroxaban has the longer half life, which may explain the increased bleeding. B. Liver dysfunction would preclude either drug. C. Potential reversal agent in PCC agents? D. Long-term safety data is lacking. 13 Cost Comparison DRUG COST/DOSE LAB COST 30 Day Total Coumadin (5mg) $1.20 $20/draw $140 Lovenox(40mg) $40 $1,200 Xarelto (10mg) $10 $300 Pradaxa (150mg) $5 $150 Arixtra (2.5mg) $100 $3, Peripheral Measures Early ambulation IPCD devices IVC filters Surgical technique 15

6 Should we change now? 1. Dabigatran looks risky from a bleeding perspective, and this is off label use. 2. Rivaroxaban is promising, but long term data is lacking, and there may be bleeding issues. 3. Apixaban has the best data, but is yet to be approved for VTE prevention. 4. Proceed with caution. 16