Internal Medicine Residency News, September 5, 2016

What did I read this week?

Contributed by Nilesh Patel, MD

Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. New England Journal of Medicine. 2016.

All of us have prescribed factor Xa inhibitors, predominantly rivaroxaban and apixaban (edoxaban is also used occasionally, but far less often as it requires a relatively narrow range of GFR—it should not be used with a GFR > 95). We may be seeing more use of these drugs in the community as they are now supported as the favored treatment of VTE in patients without cancer in the 2016 Chest Guideline Update (Chest. 2016;149(2):315-352.)

There are many arguments supporting or opposing the use of these agents. An often discussed argument is that episodes of bleeding may be difficult to treat since there is no reversal agent for factor Xa inhibitors (similar to vitamin K for warfarin, or for idarucizumab for direct thrombin inhibitors (dabigatran, N Engl J Med. 2015;373(6):511-520.) Andexanet is in trials now to be a reversal agent for all factor Xa inhibitors. It is a factor Xa decoy protein that is inactive but that retains the ability to bind factor Xa inhibitors.

The ANNEX-4 clinical trials investigating andexanet reported their preliminary results at the European Society of Cardiology and in the New England Journal. In 2015, the study group investigated the effects of andexanet in 31 healthy patients that were given either rivaroxaban or apixaban versus those given placebo (N Engl J Med 2015; 373:2413-2424). When using a bolus and 2 hour infusion of andexanet, anti-factor Xa activity was reduced in the treatment arm by over 90% compared to placebo. This effect was maintained in that group during the bolus and infusion periods. After which, levels rose to match placebo. Why is this 2 hour period considered important? That is the time in which patients should achieve a definitive hemostatic plug.

In the article published this week on the NEJM site, the ANNEX-4 investigators reported preliminary data as to whether the results from the above study are reproducible in patients with clinically active bleeds.

Study Design: Single-group, open label, prospective study.

Study Participants

• Mean age 77 years old, 35% male; 54% white
• 70% had been on anticoagulant for atrial fibrillation primarily
• All patients had some combination of CAD, CVA, DVT, PE, Afib, CHF, or DM2 history
• All patients had taken rivaroxaban, apixaban or enoxaparin (1 mg/kg) within the last 18 hours.
• All patients presented with major bleeding, defined as:
  • Potentially life threatening with clinical signs of hypoperfusion, or
  • Overt bleeding with a drop in Hgb of at least 2
  • Overt bleeding with Hgb < 8 if no baseline is available
  • Critically significant location of bleed (retroperitoneal, intracranial, pericardial, or compartment syndrome).
• 67 patients enrolled altogether and evaluated for safety of intervention; 47 of these patients were included in the efficacy analysis. Patients excluded were:
  • Those diagnosed with a thrombotic event in the last 2 weeks
  • Patients with sepsis or septic shock
  • Patients planning to go to major surgery in the next 12 hours

Intervention

Adjusted bolus dose and 2 hour infusion based on time of last drug dose and drug used.

Outcomes Collected

• Factor Xa Inhibitor levels
• Adverse events, including thrombotic events
• Independent committee evaluation of hemostatic efficacy using a hemostatic efficacy criteria previously published—rated as excellent, good or poor. As an example, if a patient was enrolled with a GI bleed, the efficacy of andexanet would be rated as:
  • Excellent: ≤10% decrease in both corrected hemoglobin/hematocrit at 12 hours compared to baseline
  • Good: >10 % to ≤20% decrease in both corrected hemoglobin/hematocrit at 12 hours compared to baseline
  • Poor: >20% decrease in both corrected hemoglobin/hematocrit

Results

• 37 of 47 patients included in the efficacy analysis had “excellent” or “good” hemostasis. For GI bleeds, for example, this would mean ≤20% decrease in hemoglobin at 12 hours compared to baseline.
  • 9 of 47 patients had poor hemostasis  (1 patient not evaluated)
    • 3 of these patients had GI bleeding and had a > 20% decline in Hb at 12 hours
    • 4 of these patients had intracranial bleeds and had a >35% increase in the size of hematoma at 12 hours
    • 2 had other sites of bleeding
• Median decrease in anti-factor Xa activity was 89-93% at the end of the infusion based on anticoagulant.
  • This effect dropped to 30-39% at 4 hours.
• 12 of 67 patients had thrombotic events (MI, CVA, or DVT) in the following 3 to 30 days.
  • Only 1 of these 12 patients had anticoagulation restarted after the bleed for which andexanet was administered

Clinic Corner: Duke Outpatient Clinic

Contributed by Lynn Bowlby, MD

It is great to see the new interns at the DOC, and the JARs and SARs lending a helping hand!

Town Hall on Thursday, Noon Conference!

• Location as per the chiefs!
• Please come with questions, and/or email , call or tell me issues that you would like discussed!

A few items:

1. New attending, mostly Monday PMs: Nia Mitchell, MD, obesity GIM researcher, and from Denver where she spent about 10 years.
2. NC Med Assist is a great option (so is Good Rx) for the uninsured pt,  Jan can help, the sign up for the pt is on line..it is a state program that pays for many, but not all meds.
3. On call: newly added to on call instructions, Death certificates are signed during business hours, brought to the DOC by the Funeral home staff. if you get called by Durham Police with any questions related to a death (or anything else!) feel free to call me on my cell.
4. Stool cards for Colon Ca screening: use code 212.11 when ordering, and if can't remember ask a nurse, if they don't know they can find out!
5. Do you speak another language? Let Aparna know, because there is a process to be an official Duke interpreter.
6. Attached Red/ Yellow/Green: you don't need to memorize the colors, but know that we try to be very thoughtful about who to contact about a DOC patient when. so if you are on Amb will likely be covering your pts and some in your PP, if you are in a unit we would only contact you for a pt you know very well or just saw. we try to use common sense!
7. And the best for las…a new nurse manager, Brenda, and new front desk supervisor, Amy. More info on Thursday!

More at Town Hall on Thursday, and please come with questions.

Lynn and Team

QI Corner

Contributed by Matthew Atkins, MD

Reminder! Patient Safety & Quality Council Meeting will be on Wednesday, September 7th at 5:30 pm in the Med-Res Library. Food will be provided.

I will introduce the Model for Improvement as a framework for approaching a quality improvement project. We will then narrow down our project ideas for this year to 2-3.

See you then!

From the Chief Residents

From the Residency Office

Duke Palliative Pain prescribing cards

Kavisha Singh reported that Palliative Care was nice enough to share the electronic version of the Duke Palliative Pain prescribing cards, which are super helpful.  We've uploaded the PDF to AgileMD. Kavisha also received a stack of insulin prescribing badge cards from Endocrinology, and has placed these cards in the Med Res Office—stop by and grab one today.

Have You Logged Your Duty Hours??

With the start of the 2016-17 academic year, the residency program is asking all house staff to log their duty hours on a daily basis.  This will allow us even closer oversight of duty hour compliance across the program.  In order to use the MedHub mobile Duty Hour app, you will need to know your actual MedHub log in as it will not accept your NetID/password log in.  If you have forgotten you main log in, please go to the main MedHub site, and select "Forgot my password."  You will then be able to re-set it via email.  Lynsey Michnowicz will be sending reminders each Wednesday to those who have not yet logged their duty hours for the week.  Thank you in advance for your attention to this task!

Opportunities for Wellness

Feeling down? Need to talk to someone? 

All trainees at Duke have FREE access to Personal Assistance Services (PAS), which is the faculty/employee assistance program of Duke University. The staff of licensed professionals offer confidential assessment, short-term counseling, and referrals to help resolve a range of personal, work, and family problems. PAS services are available free of charge to Duke faculty and staff, and their immediate family members. An appointment to meet with a PAS counselor may be arranged by calling the PAS office at 919-416-1PAS (919-416-1727), Monday through Friday between 8:00 A.M. and 5:00 P.M. For assistance after hours, residents and fellows can call the Blood and Body Fluid Hotline (115 inside DUH, 919-684-1115 outside) for referral to behavioral health resources. Another resource is Duke Outpatient Psychiatry Referrals at (919) 684-0100 or 1-888-ASK-DUKE. https://www.hr.duke.edu/pas/

Office hours for program leaders

Please feel free to stop by during these times and of course always feel free to reach out to program leaders to set up a meeting outside of these times if needed.

• Aimee Zaas: Every Monday from 3:00 p.m. to 4:00 p.m. and Thursday from 10:00 a.m. to 11:00 a.m.
• Daniella Zipkin: Wed., Sept. 7 from 11 a.m. to 12 p.m. at Pickett Rd. Clinic

Upcoming Dates and Events

• September 7 - Special lecture by Duke Nobel winner Paul Modrich. Registration is required.

• September 7 - Chief Happy Hour w/ Interns - Hope Valley Brewing

• October 4 - Intern Retreat at Museum of Life and Science

• October 8 - Stead Tread 5K Fun Run (Kempner Society)

• October 20 - Recruitment Kickoff Party, 7 p.m. to 9 p.m. at Gonza Tacos y Tequila

Useful links

• GME Mistreatment Reporting Site
• Duke Health Influenza Policy
• http://duke.exitcareoncall.com/
• Main Internal Medicine Residency website
• Main Curriculum website
• Department of Medicine
• Confidential Comment Line Note (All submissions are strictly confidential unless you chose to complete the optional section requesting a response.)

Opportunities

• https://www.phs.wakehealth.edu/public/edu.cfm
• www.FloridayPhysicianWork.com
• www.bidmc.org/CentersandDepartments/Departments/BIDHC
• http://www.careermd.com/employers/latestbulletins.aspx