Spotlight Case

1. Spotlight Case Watch the Warfarin!

2. Source and Credits • This presentation is based on the July 2011AHRQ WebM&M Spotlight Case • See the full article at http://webmm.ahrq.gov • CME credit is available • Commentary by: Raman Khanna, MD, and Margaret Fang, MD, MPH; University of California, San Francisco • Editor, AHRQ WebM&M: Robert Wachter, MD • Spotlight Editor: Bradley A. Sharpe, MD • Managing Editor: Erin Hartman, MS

3. Objectives At the conclusion of this educational activity, participants should be able to: • Appreciate challenges in the management of warfarin • Describe best practices for the management of warfarin during and after hospitalization • List recent advances in the safe management of warfarin • Recognize the risks and benefits of newer anticoagulants

4. Case: Watch the Warfarin A frail 80-year-old man with a past medical history of dementia, falls, and atrial fibrillation presented to the hospital with confusion and weakness. Based on his examination, laboratory tests, and chest x-ray, he was diagnosed with community-acquired pneumonia. He was treated with ceftriaxone and doxycycline (antibiotics) for his pneumonia. He was on long-standing anticoagulation with warfarin for his atrial fibrillation, and this medication was continued while he was in the hospital.

5. Case: Watch the Warfarin (2) After 48 hours he was clinically improved and back to his baseline, according to his daughter. Of note, his international normalized ratio (INR) was 2.4 at the time of discharge so he was appropriately anticoagulated on the warfarin. He was prescribed oral doxycycline for 5 more days for his pneumonia. There were no changes made to any of the medications he was taking before the hospitalization, including the warfarin.

6. Case: Watch the Warfarin (3) A week later, in routine laboratory testing with his primary care doctor, he was found to have an INR of 4.0 (an abnormally high level that is associated with an increased risk of bleeding). Fortunately, even though he had fallen twice in the previous week, he had no significant bleeding.

7. Background: Warfarin • Commonly prescribed anticoagulant – 30 million prescriptions a year in the U.S. • Unfortunately, has unpredictable, weight-independent effects on anticoagulation • Affected by metabolism, patient diet, other medications • Patients must have regular measurements of Internationalized Normalized Ratio (INR) and adjustments in the warfarin dose See Notes for references.

8. Background: Warfarin (2) • Subtherapeutic (low INRs) increase the risk for thromboembolism while supratherapeutic INRs raise the bleeding risk. • Risk for sub- or supratherapeutic INRs increases during hospitalization. • Because of acute illness, diet changes, new medications, etc. • INR control is worse in the peri-hospitalization period See Notes for reference.

9. Appropriate Warfarin Management Many aspects of management in this case were appropriate: • Warfarin was continued on admission • Although tempting, holding the warfarin on admission can lead to dangerously low INRs • The INR was checked at discharge • Appropriate because the patient had been started on new medications (antibiotics) • The INR was checked at one week after discharge • Patients on chronic warfarin may have the INR checked every 28 days but one week was appropriate in light of recent hospitalization See Notes for references.

10. Discharging on Warfarin However, management of this patient also had pitfalls: • Follow-up could have been scheduled sooner after discharge • Antibiotics are known to interact with warfarin, so increase in INR could have been anticipated • Appropriate to schedule follow-up within a week for this patient • Team could have communicated directly with primary care physician • Could have sent last INR result, new medication list, recommended follow-up

11. Discharging on Warfarin (2) Management pitfalls (2): • Could have educated patient and caregiver regarding warfarin management • Could have used standardized education forms and checklist,which can improve adherence and reduce adverse outcomes See Notes for reference.

12. Case (cont.): Watch Warfarin The patient’s warfarin was adjusted and his INR returned to the target range. However, this required multiple visits to the primary care physician’s office for blood tests. As the patient was debilitated and easily confused because of his dementia, the need for repeated visits placed a substantial burden on his daughter, who was his main caretaker. At the patient’s fourth visit in 2 weeks, she asked, “Is this the only way to manage his blood thinners? Will there be a better and easier way in the future?”

13. Efforts to Make Warfarin Safer • Some patients can do INR testing at home and adjust their own warfarin • Shown to be safe and acceptable to patients • Dedicated clinics that focus only on warfarin management can improve INR control • Standardized dosing algorithms for warfarin improve INR control • Standardized, patient-centered approaches seem to be more effective See Notes for references.

14. Newer Anticoagulants • New anticoagulants include factor Xa inhibitors (e.g., rivaroxaban) and direct thrombin inhibitors (e.g., dabigatran) • In general, they have fewer drug-drug interactions, are not impacted by diet, and require no dose adjustments or INR monitoring

15. Dabigatran • Approved by the FDA for use in atrial fibrillation • Dabigatran is as effective as warfarin in preventing stroke in atrial fibrillation, with potentially fewer bleeding complications • More expensive per pill than warfarin, but may be cost effective because there is no INR testing and monitoring See Notes for references.

16. Dabigatran Limitations • Dabigatran must be taken twice daily • The anticoagulant effect is not reversible if there is bleeding (unlike warfarin) • Cannot be used in patients with severe renal insufficiency

17. Take-Home Points • Best practices for managing warfarin at hospital discharge should focus on the following: • Ensuring close and timely follow-up after discharge • Improving communication between inpatient and outpatient settings regarding changes in medications, clinical status, and warfarin treatment plan • Educating patients and their caregivers to improve their understanding of and adherence to the warfarin regimen, particularly among patients newly started on warfarin

18. Take-Home Points (2) • Standardizing systems of care through lab integration and improved communication between inpatient and outpatient settings to improve the safe use of warfarin within a health care system • Switching from warfarin to newer oral anticoagulants, particularly for patients with unstable INRs or those in whom lab monitoring has proven to be a significant burden