Changing the Ambulatory Training Paradigm. Design and Implementation of an Outpatient Pulmonology Fellowship Curriculum.

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ANNALSATS Articles in Press. Published on 10-February-2016 as 10.1513/AnnalsATS.201601-009PS

Changing the Ambulatory Training Paradigm: The Design and Implementation of an Outpatient Pulmonology Fellowship Curriculum Stacey M. Kassutto1, C. Jessica Dine1, 2, Maryl Kreider1, Rupal J. Shah3 1. Division of Pulmonary, Allergy & Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 2. Leonard Davis Institute of Health Care Economics, University of Pennsylvania, Philadelphia, PA 3. Division of Pulmonary, Critical Care, Allergy & Sleep Medicine, University of CaliforniaSan Francisco, San Francisco, CA Corresponding Author: Stacey M. Kassutto Hospital of the University of Pennsylvania 839 W. Gates Building Philadelphia, PA 19004 [email protected] Financial Support: There are no financial disclosures or sources of funding for this study. The authors have no disclosures or disclaimers. Running Head: Implementation of an Outpatient Fellows Curriculum Descriptor: Professional education/training/certification Mesh Keywords: ambulatory care; graduate medical education; fellowship training; pulmonary medicine Data Supplement: This article has a data supplement, which is accessible from this issue's table of contents online at www.atsjournals.org

Word Count: 1999

Copyright © 2016 by the American Thoracic Society


Abstract Rationale: The Accreditation Council for Graduate Medical Education has mandated that pulmonary fellows practice evidence-based medicine “across multiple care settings.” Currently, most clinical fellowship training is inpatient based, suggesting, more robust fellowship training in outpatient pulmonology is needed. No standardized ambulatory pulmonary curriculum is currently available. Objectives: To design, implement and test the feasibility of a standardized, case-based outpatient curriculum implemented for pulmonary fellows at the Perelman School of Medicine at the University of Pennsylvania. Methods: A list of 20 topics in ambulatory pulmonology was generated and used to create a series of literature-based teaching scripts, which served as the foundation for twice-monthly small group teaching sessions. Prior to implementation, fellows were asked to complete a survey regarding impressions of their existing outpatient training and their competency in ambulatory patient care. Participants were surveyed again at 6 and 12 months thereafter. Measurements and Main Results: Fellow survey respondents reported that the curriculum improved the overall ambulatory educational experience. Prior to implementation, only 6 of 12 fellows (50%) agreed that their current instruction on relevant outpatient pulmonary topics was adequate compared with 100% post-curriculum (p= 0.01, n=10). In addition, only 5 (42%) fellows initially agreed or strongly agreed that their current outpatient educational experience had prepared them well for independent pulmonary practice compared with 90% on the 12month survey (p=0.02).


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Conclusions: We created and demonstrated the feasibility of a standardized outpatient pulmonary curriculum that positively impacted fellows’ perceived competency in ambulatory pulmonology. Additional assessment of knowledge, performance outcomes and applicability at other institutions is needed.

Abstract Word Count: 254



Pulmonary fellowship trainees are expected to obtain the knowledge and skills necessary for independent medical practice. Accordingly, the Accreditation Council for Graduate Medical Education (ACGME) set forth curricular milestones and learning objectives for trainees in pulmonary medicine. Adopted in July 2014, these milestones were the result of a consensus of the American College of Chest Physicians, Society of Critical Care Medicine, American Thoracic Society and the Association of Pulmonary and Critical Care Medicine Program Directors.1-4 The milestones and entrustable professional activities (EPAs) require fellows to practice evidence-based pulmonary medicine "across multiple health care settings." Many of the required medical knowledge and patient care competencies are encountered only in outpatient care settings.4 However, the majority of clinical training during pulmonary fellowship remains inpatient focused. In fact, the ACGME requires that fellows spend only 7% of training in the outpatient setting (one half-day of clinic weekly for 30 months in a 36-month fellowship).5 This current training paradigm often delays the honing of outpatient management skills. Thus, relying entirely on direct engagement with patients in a continuity clinic experience for all ambulatory education is likely insufficient preparation for independent practice after fellowship. In order to meet a similar educational need in ambulatory internal medicine, the Yale School of Medicine developed a literature-based syllabus that covers a wide array of primary care topics. This collection of case-based teaching scripts is published as the “Yale Office-based Medicine Curriculum” and is now used in more than 170 internal medicine residency training programs throughout the country.6,7 However, to the best of our knowledge, no standardized outpatient curriculum is currently available for pulmonary fellowship training.


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In response to this educational need, we implemented a structured case and evidencebased outpatient fellowship curriculum at the Perelman School of Medicine at the University of Pennsylvania (PSOM). We hypothesized that this curriculum would provide a more robust and educational outpatient experience for the pulmonary fellow as assessed by a survey of trainees following the curriculum’s implementation. Some of the results of these studies have been previously reported in the form of an abstract.8

Methods

Topic Selection A novel, standardized outpatient pulmonary fellowship curriculum was developed and piloted by the faculty and fellows at PSOM beginning in October 2014. Twenty core topics were selected for the pilot curriculum (Table 1). The curriculum targeted disease states and clinical management areas that were uncommonly seen in the inpatient setting or unique to outpatient care. The list was further narrowed based on faculty expertise and informal fellow feedback. The subspecialty milestones were also reviewed in the selection of the pilot curriculum. Additional topics for a longitudinal 24-month curriculum were also selected (Table 2).

Content Delivery To create a curriculum that was feasible, sustainable and potentially reproducible elsewhere, all conferences were delivered in a small group setting using a literature-based teaching script. These teaching scripts followed a standardized case-based format inspired by the previously



published Yale Office-Based Medicine Curriculum.6,7 Faculty were instructed to focus content on practical clinical management and decision-making. Each script included the following: stated learning objectives; clinical case vignettes; illustrative clinical questions with evidence-based answers; and references to key articles. Paper copies of the teaching scripts were distributed at the beginning of each conference. Electronic copies were distributed to the fellows and were also made accessible via the “MedHub” online education portal. They remain available for future faculty use in this conference series.

Conference Timing The pilot outpatient curriculum took place from October 2014-June 2015, beginning after the conclusion of our core Summer Lecture Series (July-September). Conferences were held twice monthly prior to fellows’ clinic on Thursday afternoons and lasted approximately 30 minutes. The conference timing was selected based upon fellow and faculty availability.

Faculty and Fellow Participation Fellows from all training cohorts were invited to the conferences but attendance was not required. Faculty volunteers were solicited at the beginning of the academic year to lead conferences. Faculty participation in conference authorship was voluntary. They were not financially incentivized by the University to participate. All faculty preceptors were considered experts in the assigned topic and authored original teaching scripts for use during each conference (see sample handout in Appendix A).


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Curriculum Evaluation To assess the impact of the curriculum, this prospective cohort study utilized a de-identified, electronic, 33 question survey (see sample in Appendix B) assessing fellows’ impressions of the existing outpatient pulmonary fellowship experience. In addition, we asked fellows to provide a self-assessment of individual competencies as outpatient pulmonologists. Fellow conference attendance was also tracked. The research proposal was submitted to the University of Pennsylvania’s Institutional Review Board and deemed to meet criteria for exemption from review and obtainment of informed consent. Study data from the survey were de-identified, collected and managed using REDCap electronic data capture tools hosted at the University of Pennsylvania.9 The survey was administered prior to the curriculum’s implementation, and 6 and 12 months thereafter. We also recorded attendance at each conference. We used two-sample test of proportions to evaluate changes in response to each question. P values less than 0.05 were considered significant. Analyses were performed using STATA v13.0 (STATA Corp., College Station, TX).

Results

Nineteen conferences took place throughout the pilot curriculum (“Introduction to Billing” was combined with another clinical topic). A total of 12 (4 female, 8 male) out of 17 eligible fellows agreed to participate in the curriculum evaluation survey. Five (42%) of the participants were first year fellows and 7 were from upper year cohorts (Table 3). Because 2 senior fellows



graduated prior to administration of the 12-month follow up surveys, only 10 fellows completed all 3 surveys.

Conference Attendance and Faculty Participation Seventeen faculty members volunteered to participate in both authorship and leadership of the conference sessions. Fellow attendance at conferences was tracked throughout the pilot curriculum. First year fellows had the highest attendance rate (72%). Overall attendance for all fellows in the study was 45%. Pooled attendance was significantly lower due to the poor attendance of the third-year fellowship class.

Perceptions of Ambulatory Education Overall, fellow survey responses demonstrated that the curriculum improved fellows’ perception of the ambulatory educational experience. When asked on the pre-implementation survey about likelihood to attend a pre-clinic conference dedicated to outpatient pulmonary medicine topics, 11 fellows (92%) agreed or strongly agreed that they were likely to attend and 10 (83%) felt that outpatient pulmonary clinic is crucial to overall pulmonary fellowship education (Table 4). Prior to the new outpatient curriculum, only 6 fellows (50%) agreed or strongly agreed that the current instruction on clinically relevant outpatient pulmonary topics was adequate, compared to 100% post-curriculum (p=0.01). In addition, only 5 fellows (42%) agreed or strongly agreed that their current outpatient educational experience had prepared them well for independent pulmonary practice prior to the curriculum’s implementation, compared with 90% on the 12-month follow up survey (p=0.02).


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Most fellows consistently agreed that their ambulatory experience was a crucial part of their fellowship education (83% vs. 90%, p=0.64). However, the new ambulatory curriculum led to significant improvement in satisfaction with the structure and education in outpatient clinic. 70% agreed or strongly agreed that they were satisfied with their ambulatory education on the 12-month follow up survey compared to only 25% pre-curriculum (p=0.03). Following the curriculum’s implementation, more fellows also agreed that ambulatory education was a strength of the program, although this change was not statistically significant (58% precurriculum vs. 80% post-curriculum, p=0.27). Responses on the six month survey showed a similar trend (Appendix C). To better understand the impact of this educational initiative, fellows were asked to rate their comfort in managing specific disease states that were either included or excluded as topics in the pilot curriculum. However, we were unable to compare perceived competency in management of these diseases due to the small number of survey participants.

Discussion

With the development of case-based teaching scripts, we created a standardized curriculum to cover core pulmonary ambulatory content and address this unmet educational need in fellowship education. The creation of this collection of teaching scripts allows for easy distribution as a conference syllabus, thus eliminating the need for significant future faculty time investment to create ambulatory educational content de novo. In addition, it also reduces



the need for specialized expertise in all of the included topics, which may be helpful in smaller training programs. The curriculum is currently in its second year at PSOM. Peer-review of the teaching scripts is on-going, with a plan for distribution to other interested pulmonary fellowship training programs upon completion. Although not directly measured, it was informally noted that conference timing and duration could be improved. Accordingly, the conference has been changed to a morning conference that lasts 60 minutes. We chose to continue with a traditional conference format to facilitate discussion of clinical management decisions. However, a benefit of the teaching scripts is that it allows alternative formats, including a flipped-classroom using online education modules, to be considered. This could improve participation of the senior research fellows. We will evaluate the effectiveness of alternative formats in future study. Our results from this pilot study suggest that the curriculum had a positive impact on fellow ambulatory education. Prior to the curriculum’s implementation, survey responses indicated that fellows felt under-prepared for independent outpatient pulmonary practice and were generally dissatisfied with their ambulatory education. Following the initiation of this curriculum, responses demonstrated overall improved perceptions of the ambulatory educational experience and preparedness for independent outpatient practice. The fellows also demonstrated their enthusiasm for more robust ambulatory education through their conference attendance. Although our pooled attendance rate was low, first year attendance was quite high and was among the best for any of the division’s daily conferences. In addition, the recruitment of 17 faculty members to participate in authorship and leadership of the conferences demonstrates a high level of faculty engagement with ambulatory teaching.


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There are limitations to the educational approach described. Although the initial iteration of teaching scripts has been created, an annual review for updates in the literature and changes to management recommendations will be necessary. Dissemination of content to other sites raises interesting questions regarding generalizability of content needs to all training programs, but also an opportunity to study alternative teaching formats. We believe this is a needed first step in improving fellow education in outpatient pulmonology. Our evaluation of the curriculum’s impact on trainee education is limited. The survey responses represent the subjective self-reported impressions of a small cohort of fellows at one academic medical center, raising issues with respect to both sample size and overall generalizability of our findings. Because of the small number of participants, we were also unable to assess for inter-rater reliability. However, we have generated important preliminary data supporting the value of a structured outpatient ambulatory curriculum. Without an adequate control group of curriculum non-participants, it is difficult to determine if the noted improved comfort and self-perceived competency in ambulatory care is directly attributable to our new educational initiative, the continued natural developmental progression seen from junior to senior trainee, or a combination of both. Furthermore, we would expect some variation in competency by training cohort, even upon completion of the curriculum. Thus, future inquiry is needed to explore the impact of this curriculum on trainee competency in ambulatory EPA’s, attainment of the increasingly important milestones outlined by the ACGME, and performance on national board exams. This would best be accomplished in a prospective multi-institution study with more objective methods of assessment. However, these early results indicate that this curriculum is a practical and generally well-received



approach to addressing this previously unmet educational need and provides the basis for future study. In conclusion, we have developed a feasible and standardized approach to improving ambulatory education for trainees in pulmonary fellowship. Following implementation, fellows reported an improved sense of competency in outpatient pulmonary medicine and preparation for independent post-graduate practice. Additional research will be required to assess the curriculum for knowledge and performance outcomes, to demonstrate sustainability over time, and to test applicability at other institutions.


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Acknowledgements We would like to thank the following faculty who authored teaching scripts for use in this curricular endeavor: Gregory Tino, MD; Joshua Diamond, MD MSCE; Scott Manaker, MD PhD; David Lipson, MD; John Hansen-Flaschen, MD; Daniel Dorgan, MD; Michael Sims, MD MSCE; John Reilly, MD MSCE; Bernie Sunwoo, MB BS; Judd Flesch, MD; Neha Darrah, MD; Steven Weinberger, MD; Sara Lyon, MD MSCE; Jason Fritz, MD; and Jamie Bessich, MD.



References

1. The Accreditation Council for Graduate Medical Education and the American Board of Internal Medicine Working Group. The Internal Medicine Milestone Project; 2014 July [accessed 20 June 2014]. Available from: http://www.abim.org/pdf/milestones/internalmedicine-milestones-project.pdf 2. Nasca TJ, Philibert I, Brigham T, Flynn TC. The next GME accreditation system—rationale and benefits. N Engl J Med 2012; 366(11):1051-1056. 3. The Accreditation Council for Graduate Medical Education and the American Board of Internal Medicine Working Group. The Internal Medicine Milestone Project; 2014 July [accessed 20 June 2014]. Available from: http://www.acgme.org/acgmeweb/Portals/0/PDFs/Milestones/InternalMedicineSubspecial tyMilestones.pdf. 4. Fessler HE, Addrizzo-Harris D, Beck JM, et al. Entrustable professional activities and curricular milestones for fellowship training in pulmonary medicine: report of a multisociety working group. CHEST 2014; 146: 813-34. 5. Accreditation Council for Graduate Medical Education. ACGME program requirements for graduate medical education in pulmonary disease; 2011 February [accessed 13 June 2014]. Available from: http://www.acgme.org/acgmeweb/Portals/0/PFAssets/2013-PR-FAQPIF/149_pulmonary_disease_int_med_07132013.pdf. 6. Yale Office-based Medicine Curriculum, eds. Julie R Rosenbaum, Seonaid F. Hay, and Laura M. Whitman, 9th edition. New Haven, CT: Yale University, 2005. 7. Yale Office-based Medicine Curriculum: Overview. New Haven, CT: 2015 July [accessed 30 August 2014]. Available from: https://medicine.yale.edu/intmed/obm/about/ 8. Kassutto SM, Dine CJ, Kreider M and Shah RJ. Implementation of an Outpatient Pulmonary Fellows' Curriculum: A Structured Case-Based Approach. American Thoracic Society International Conference [abstract]. May 1, 2015. 9. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support, J Biomed Inform. 2009 Apr; 42(2):377-81.


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Table 1. Topics included in the pilot ambulatory conference curriculum: October 2014-June 2015. Chart Documentation

Introduction to Interstitial Lung Disease

Introduction to Billing for Outpatient

Idiopathic Pulmonary Fibrosis

Services Oxygen Delivery/Inhaler Techniques

Introduction to Lung Transplantation

Asthma

Pulmonary Hypertension

Asthma in Pregnancy

Chronic Venous Thromboembolic Disease

COPD I-Inhaled Therapies

Initial Evaluation of Hemoptysis

COPD II-Roflumilast and Azithromycin

Evaluation of the Lung Nodule

Chronic Cough

Neuromuscular Pulmonary Disease

Bronchiectasis

Pleural Effusion Management

Reactive Airways Dysfunction Syndrome

Palliative Care in for Patients with Advanced Lung Disease



Table 2. Topics for inclusion in year 2 of a 24-month longitudinal curriculum. * Tuberculosis & Non-tuberculous

Community Acquired Pneumonia & Lung

Mycobacterial Infections

Abscess

Pre-operative Evaluation

Occupational Lung Disease

Management of the “Difficult” Patient

Tobacco Cessation

Cystic Fibrosis

Introduction to Pulmonary Rehabilitation

Obstructive Sleep Apnea & Obesity

Pulmonary Manifestations of

Hypoventilation Syndrome

Rheumatologic Disease

Post-lung Transplant Complications

Chronic Aspiration

Cystic Lung Diseases

HIV-Associated Lung Disease

Respiratory Complications of BMT and

Care Transitions of the Pediatric Pulmonary

Solid (Non-Lung) Organ Transplant

Patient

Asbestosis and Pleural Lung Diseases

Practical Clinical Approach to CPET

Goals of Care/End of Life Discussions

COPD III- Referral for LVRS/Transplant

* Curriculum development is ongoing for the 2015-2016 academic year


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Table 3. Description of Fellow Participants in the Curriculum Survey. A summary of fellow survey participant characteristics including gender, cohort, clinical interests and research focus. Gender Male

8 (33%)

Female

4 (66%)

Fellowship Cohort First Year

5 (42%)

Second Year

5 (42%)

Third Year

2 (16%)

Career Pathway/Advanced Degrees Clinical Research

4 (33%)

Health Policy Research

3 (25%)

Advanced Clinical Training

1 (8%)

Basic Science

3 (25%)

Combination

1 (8%)

Primary Clinical Interest Critical Care

7 (58%)

General Pulmonary

1 (8%)

Interventional Pulmonary

1 (8%)

Undecided

3 (25%)

Continuity Clinic Site Perelman Center (HUP)

9 (75%)

Philadelphia VA Medical Center

3 (25%)



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Table 4. Summary of fellow impressions of the ambulatory education program before and after curriculum implementation. Pre-Curriculum

Post-Curriculum

P value

12 month FollowUp My outpatient pulmonary clinic has

5 (42%)

(9) 90%

0.02

10 (83%)

(9) 90%

0.64

6 (50%)

(10) 100%

0.01

3 (25%)

(7) 70%

0.03

7 (58%)

(8) 80%

0.27

prepared me well for independent pulmonary practice My outpatient pulmonary clinic (as it is currently structured) is a crucial part of my overall pulmonary fellowship education With the current outpatient curriculum structure, I am gaining/have gained appropriate instruction and teaching on clinically relevant topics in pulmonary medicine I am satisfied with the current structure and education in my outpatient pulmonary clinic The outpatient pulmonary clinic experience is a strength of the program The pre-curriculum survey was distributed to 12 fellows. The post-curriculum 12-month follow up survey was administered to 10 participants due to graduation of 2 senior fellows.


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Online Data Supplement Changing the Ambulatory Training Paradigm: The Design and Implementation of an Outpatient Pulmonology Fellowship Curriculum Stacey M. Kassutto, C. Jessica Dine, Maryl Kreider, Rupal J. Shah

Items contained: 1. Appendix A: Sample teaching script 2. Appendix B: Sample survey distributed to fellows 3. Appendix C: Supplemental table of 6 month survey data.



APPENDIX A: SAMPLE TEACHING SCRIPT Venous Thromboembolism - Outpatient Management John P. Reilly MD MSCE Educational Objectives: 1. Review the longer term treatment options for acute PE and DVT 2. Discuss the relative benefits and evidence for each anticoagulant 3. Review the contraindications and concerns with each anticoagulant, including the new direct thrombin inhibitors and factor Xa inhibitors 4. Discuss the decision making process for deciding on length of anticoagulation therapy 5. Review the inherited thrombophilias and when to test for them CASE ONE: Mr. S is a 27 year old male professional soccer player with no past medical history who presented to the hospital with acute onset dyspnea and chest pain after a 12 hour flight from a soccer tournament in Asia. On physical exam he is tachycardic, mildly tachypneic, normotensive, and not hypoxic. His right lower extremity has trace to 1+ edema, while his left lower extremity has no edema. CXR is clear. He is subsequently diagnosed via a CT angiogram with an acute PE, as well as a proximal R lower extremity DVT. He is started on LMWH immediately and admitted. The next day he remains stable with improving symptoms and is preparing for discharge. He will follow up in your clinic. Question 1: What anticoagulant should this patient be discharged on? What are your options? What is the evidence? Initial Anticoagulation Choices: Low Molecular Weight Heparin – Grade 2B recommendation by ACCP as initial anticoagulation over IV unfractionated heparin. Compared with IV UFH, LMWH results in lower mortality, fewer recurrent thromboembolic events, and less major bleeding. It also has greater bioavailability, more predictable pharmacokinetics, fixed dosing, and a decreased likelihood of thrombocytopenia. Concerns have been raised in obesity and low body weight (less predictable pharmacokinetics) as well as with renal insufficiency. Fondaparinux (SC) – Antithrombin III mediated selective inhibitor of factor Xa. ACCP suggests fondaparinux as an alternative to LMWH and over IV UFH for initial anticoagulation. Fondaparinux compared to IV UFH resulted in similar outcomes. LWMH and fondaparinux have only been compared for acute DVT. In 2,205 patients with DVT, mortality, recurrent thromboembolic disease, and major bleeding were similar (Buller et al, 2004). Unfractionated Heparin (IV) – IV drip requiring routine monitoring of PTT. Used in several specific situations; (1) Persistent hypotension due to acute PE. (2) Increased risk of bleeding – UFH is easily reversed with protamine. (3) Thrombolysis is being considered. (4) Concerns about subcutaneous absorption – obesity, anasarca. (5) Renal insufficiency. SC UFH is also reasonable but not commonly used. Rivaroxaban – Not currently recommended given lack of experience, but see below.


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Long Term Anticoagulation Choices: All patients with acute proximal DVT of the leg and/or PE (provoked or unprovoked) should be anticoagulated for at least 3 months if not contraindicated (Grade 1B recommendation). Comparisons with shorter durations such as 4-6 weeks have all show higher rates of recurrent VTE and/or extension of VTE. ACCP Guidelines (2012): In patients with DVT of the leg or PE and no cancer, we suggest vitamin K antagonist therapy over LMWH, dabigatran, or rivaroxaban for long-term therapy (Grade 2C). In patients with DVT of the leg or PE and cancer, we suggest LMWH over VKA therapy, dabigatran, or rivaroxaban for long term therapy (Grade 2B). Warfarin – Vitamin K antagonist that suppresses the production of the vitamin K-dependent clotting factors (II, VII, IX, and X). Long-term treatment with warfarin has excellent evidence. In a Cochrane review of 8 studies with 2,994 patients long-term treatment of warfarin dramatically reduced recurrent VTE compared to early cessation (Hutten et al. 2006). Limitations include: need to monitor the INR, drug–drug interactions, need to overlap with heparin therapy, effects of diet, and warfarin induced skin necrosis. LMWH – Preferred therapy for pregnancy and malignancy. RCTs have demonstrated no difference in LMWH versus warfarin in recurrent VTE, bleeding, or mortality, and may have decreased post-thrombotic syndrome. Several RCTs compared LMWH to warfarin in cancer and demonstrated conflicting results. A Cochrane meta-analysis concluded that LMWH was associated with reduced recurrent VTE in cancer and no change in bleeding or mortality (Lee et al. 2003, Hull et al. 2006, Meyer et al. 2002, Deitcher et al. 2006, Akl et al. 2014). Dabigatran – Direct thrombin inhibitor. Thrombin (factor IIa) is the final enzyme in the clotting cascade leading to fibrin formation, and is cleaved from prothrombin by factor Xa. The orally administered drug is a pro-drug that is converted in the liver to the active form. Half-life is 12-17 hours in normal renal function. Pills must stay in their bottle and not in a pill box as the drug breaks down with moisture and only lasts 4 months. Cannot use in renal disease. Interacts with many drugs (Rifampin, ketoconazole, verapamil), and needs acid in stomach to activate (i.e. interacts with PPIs). Cannot be reversed (maybe dialysis). Evidence in VTE: 1. RECOVER I – 2539 patients with acute VTE randomized to six months of dabigatran (150 mg BID) vs. warfarin after 7 days of parenteral anticoagulation. Recurrent VTE occurred in 2.4% vs 2.1%, VTE-related deaths 0.1 vs. 0.2, major bleeding 1.6 vs. 1.9, any bleeding 16.1 vs. 21.9 (Shulman et al. 2009, NEJM). 2. RECOVER II – 2589 patients with acute VTE very similar results – recurrent VTE 2.3% vs 2.2%, major bleeding 1.2% vs 1.7% (Shulman et al. 2014, Circulation). Rivaroxaban – Oral direct factor Xa inhibitor, inactivates circulating and clot bound factor Xa. Metabolized by the kidney and interacts with dual inhibitors of CYP-3A4 and P-glycoprotein (azoles, ritonavir). Cases of liver injury have also been reported. Rivaroxaban has been studied as an initial anticoagulant that continues as long-term.



Evidence in VTE: 1. EINSTEIN-DVT – 3449 patients with acute, symptomatic DVT randomized to oral rivaroxaban alone (15 mg BID for 3 weeks, than 20 mg daily) vs. enoxaparin followed by VKA. Recurrent VTE 2.1% vs. 3%, bleeding 8.1% vs. 8.1% (Bauersachs et al. 2010, NEJM). 2. EINSTEIN-PE – 4,832 patients with acute symptomatic PE randomized to rivaroxaban versus enoxaparin followed by VKA. Recurrent VTE 2.1% vs 1.8%, bleeding 10.3% vs 11.4%, major bleeding 1.1% vs 2.2% (Buller et al, 2012, NEJM). Apixaban – Oral direct factor Xa inhibitor. Similar to rivaroxaban. Evidence in VTE: 1. AMPLIFY – 5395 patients with acute VTE randomized to apixaban (10 mg BID for seven days than 5 mg BID for 6 months) vs enoxaparin followed by warfarin. Recurrent VTE 2.3% vs. 2.7%, bleeding 4.3% vs. 9.7% (Agnelli et al. 2013, NEJM). Case Continued: Mr. S was discharged on warfarin therapy with follow up in pulmonary clinic and coumadin clinic. He reports that he takes his warfarin every day as prescribed but in the last two weeks he has had INRs that have been >3.0 and

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