WHY ANTICOAGULATION? Jean M. Connors, MD Assistant Professor

WHY ANTICOAGULATION? Jean M. Connors, MD Assistant Professor

WHY ANTICOAGULATION? Jean M. Connors, MD Assistant Professor of Medicine Medical Director, Anticoagulation Management Services Hematology Division Thrombosis Thrombosis (Greek: ) is the ) is the formation of a blood clot (thrombus; Greek: ) is the ) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is

injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot that breaks free and begins to travel around the body is known as an embolus http://en.wikipedia.org/wiki/Main_Page Hemostasis Pro-clotting <----------> Anti-clotting anticoagulation Virchow's triad

Kyrle P A , Eichinger S Blood 2009;114:1138-1139 2009 by American Society of Hematology Upsetting the Balance Atrial fibrillation--irregular heart rhythm Blood pools and slows in the atrium and forms clots Clots can travel out of the heart, results in thromboembolism usually arterial

Mechanical heart valves Artificial surface activates clotting factors and platelets, also a mechanism of arterial thromboembolism The Heart The Heart Upsetting the Balance Atrial fibrillation--irregular heart

rhythm Blood pools and slows in the atrium and forms clots Clots can travel out of the heart, results in thromboembolism usually arterial Mechanical heart valves Artificial surface activates clotting factors and platelets, also a mechanism of arterial thromboembolism The Heart

The Heart Upsetting the Balance Stroke Atherosclerosis: carotid artery plaques Cardiac thrombosis Congestive heart failure Arterial thromboembolic events without obvious cause Major Veins and Arteries

Major Veins and Arteries Leg Veins Upsetting the Balance Venous thromboembolism (VTE) Deep vein Superficial vein Pulmonary embolus Risks: Surgery Orthopedic joint replacement surgery

Hips, knees Trauma surgery for fractures Bed rest/hospitalization Upsetting the Balance Risks for blood clots Cancer Certain kinds or certain treatments Usually venous but sometimes arterial Antiphospholipid syndrome Auto-immune disorder, both venous and arterial clots

Inherited blood clotting disorders Factor V Leiden Prothrombin gene mutation Protein S deficiency Protein C deficiency Antithrombin deficiency

What is Anticoagulation? What is anticoagulation? Use of prescription medications that make your blood less likely to clot. These medications are called anticoagulants. Also known as blood thinners or anticlotting medicines. They make it harder to form a clot. Goals of

Anticoagulation Goals of anticoagulation Prevent a new blood clot from getting bigger Prevent a recurrent blood clot Prophylaxispreventing a blood clot in someone is who at high risk for having a blood clot but has never had one How Long? Goals of anticoagulation Depends on the risk factor or reason

Temporary risks or provoked blood clots can be treated with limited duration of anticoagulation After surgery Permanent risks, or unprovoked blood clots, often require indefinite, lifelong, continued anticoagulation Atrial fibrillation ANTICOAGULANTS OLD 1922 Heparin: first anticoagulant developed

for human use 1954 Warfarin: first oral anticoagulant IN BETWEEN 1996 LMWH= Lovenox, Fragmin 2001 Fondaparinux=Arixtra NEW ORAL ANTICOAGULANTS 2010 Dabigatran=Pradaxa 2011 Rivaroxaban=Xarelto 2013 Apixaban=Eliquis What Kind? Goals of anticoagulation

Different types depending on need: Intravenous Heparin Bivalirudin argatroban Subcutaneous injections Enoxaparin, dalteparin fondaparinux Oral Warfarin new oral anticoagulants

The End Talk to your health care providers: Physician Nurse, nurse practitioner, physician assistant BWH Anticoagulation Management Service clinician Importance of INR Monitoring Laura Hill RPh, Pharm D Anticoagulation Clinic Brigham and Womens Hospital

Objectives Define INR and how it relates to warfarin Understand the importance of warfarin therapy and the need for close INR monitoring Appreciate what factors affect your INR level Review the different ways to monitor your INR What is an INR? The International Normalized Ratio (INR) is a measurement of how long it takes blood to form a clot. For most people, the INR result that provides

the best balance between the risk of bleeding and clotting is between 2.0 and 3.0 this is called the target INR range. How Does Warfarin Work? Your body uses vitamin K to produce some of the clotting factors that helps blood to clot Warfarin (Coumadin) works by interfering with how your body uses vitamin K Goals of Warfarin Therapy

Decrease the time it takes the body to form a clot Fluctuations in INR Prescription medications Herbal supplements and vitamins Medications you buy 'over the counter' Diet Health Alcohol intake and/or smoking Activity level Target INR Ranges

Therapeutic Recommendations For Warfarin Target INR Ranges As your INR increases your risk of clotting decreases As your INR increases your risk for bleeding increases

Critical INR values INR > 4.0 risk of bleeding INR < 1.5 risk of developing a clot How Often to Test INR How often you test your INR will vary from person to person.

Extra tests may be required in certain situations. For instance, a change in medication may affect your warfarin metabolism and alter your INR. Warfarin Dosage Requirements Your target warfarin dose depends on many factors, including genetics, and is unique to each individual. For one person, a small warfarin dose may be enough to reach their target INR, while another person may need to take 2-3 times (or more) as

much to achieve the same effect. Options for Testing INR Lab Testing: Doctors office Outpatient lab VNA/Home draw services Options for testing INR Point-of-care testing: Roche CoaguChek XS INR system

Alere INRatio2 PT/INR monitor Travel and INR Monitoring Test your INR before leaving on your trip Keep your activity and eating habits as close to your regular routine as possible It may be possible to send an INR order to the lab while you are away Missed Doses and INR Avoid missing doses of warfarin Make warfarin a part of your daily routine NEVER take a double dose!

Keeping INR Stable Your keys to success: Take your warfarin exactly as prescribed. Have your INR checked regularly. Keep your vitamin K intake and activity consistent from day to day. Key Points in INR Monitoring INR tests are conducted for your safety. Take your warfarin exactly the way your

warfarin manager tells you. Report any changes in medications, and any significant changes in your daily routines and diet, to your warfarin manager. References Ageno W, Gallus AS, Wittkowsky A, et al, Oral Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest, 2012, 141(2 Suppl):e44-88. Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. The European Atrial Fibrillation Trial Study Group. N Engl J Med 1995; 333:5. Jones M, McEwan P, Morgan CL, et al. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population. Heart 2005; 91:472.

White HD, Gruber M, Feyzi J, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007; 167:239. Oake N, Jennings A, Forster AJ, et al. Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic r eview and meta-analysis. CMAJ 2008; 179:235. http://www.mayoclinic.org/tests-procedures/prothrombin-time/basics/results/prc-20013300 http://www.ptinr.com/ Blann AD, Fitzmaurice DA, Lip GY; Anticoagulation in hospitals and general practice.; BMJ. 2003 Jan 18;326(7381):153-6. Shalansky S, Lynd L, Richardson K, et al; Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007 Sep;27(9):1237-47. Brigham and Womens Hospital

Anticoagulation Management Service Living with Warfarin: What Affects your INR? Gina Dube, PharmD, CACP, RPh October 25, 2014 Objectives Identify the factors that influence the INR Understand ways to improve warfarin therapy with lifestyle changes Identify disease states which may influence warfarin therapy

What is Warfarin? Anticoagulant Medication that is used to reduce the formation of blood clots Commonly referred to as ablood thinner Increasing the time it takes for blood clot How Does Warfarin Work? Blocks a process that uses Vitamin K- to make clotting factors, therefore reducing the bodys ability to make blood clots

Holmes, 2012 What Affects your INR?

Diet Missed doses Alcohol Other Medications Exercise Illness/Infection Dietary supplements Vitamins Smoking Holding for procedures 44

Diet and Vitamin K Foods rich in Vitamin K can cause a decrease in your INR You do not need to eliminate Vitamin K containing foods from your diet Vitamin K foods have been shown to keep your INR levels more stable 45

Vitamin K Content of Selected Vegetables Description Serving Vitamin K (mcg/measure) VERY HIGH (>500mcg/serving) Kale cooked 1 cup

1062 Collards frozen, cooked 1 cup 1059 Spinach frozen, cooked 1 cup 1027

Beet greens cooked 1 cup 697 Dandelion greens cooked 1 cup 579

Turnip Greens frozen, cooked 1 cup 851 HIGH (200-500 mcg/serving) Mustard greens cooked 1 cup 419

Brussels sprouts cooked 1 cup 300 Broccoli cooked 1 cup 220

Onion scallions, raw 1 cup 207 Diet and Vitamin K Eating more Vitamin K foods than usual can decrease your INR Vitamin K =

INR Eating less Vitamin K foods than usual can increase your INR 47 Diet and Vitamin K Consistency is the key! Your INR levels are based on your current vitamin K intake Call your warfarin manager to report any

drastic changes in your diet 48 What if I Forget to Take My Warfarin? If you remember later the same day, take it as soon as you remember. If you dont remember until the next day, call your warfarin manager. DO NOT TAKE

EXTRA DOSES TO CATCH UP 49 Alcohol Alcohol interferes with the livers ability to breakdown warfarin Alcohol

INR Drinking more than 2 alcoholic drinks in one day can increase your risk of serious bleeding while taking warfarin Alcohol One alcoholic drink = 51 Drug Interactions

Warfarin interacts with many medications and supplements including: Prescription (e.g. Antibiotics, steroids.) Over-the -Counter Medications (e.g. Tylenol, Advil, Aleve, Motrin) Vitamins Herbal Supplements Dietary Supplements 52 Dietary Supplements Many supplements can interact with warfarin Some multi-vitamins and meal replacement shakes

contain vitamin K Consult your healthcare provider prior to starting any supplements Other Interactions Read all labels Nutritional Supplements Bars Drinks 54

Drug Interactions Your current INR level is based on the medications that you currently take. Notify your warfarin manager before you START, STOP or CHANGE ANY MEDICATIONS Warfarin can also interfere with the way other medications work 55 Exercise and INR

Increase or decrease in physical activity can alter the INR level activity = INR activity = INR BE CONSISTENT! Illness Let your warfarin manager know if you experience vomiting diarrhea or constipation Cold, fever, flu Infection

other serious illness These symptoms may affect your INR and require a 57 Disease States and Warfarin Increased effect Decreased effect Hyperthyroidism Liver disease Crohns disease Congestive heart

failure Hypothyroidism Fat malabsorption 58 Smoking and INR Cigarette smoking = INR Cigarette smoking = INR Notify your warfarin manager if you start

smoking or decide to quit smoking. 59 Procedures Communication with all providers (doctors, dentists, pharmacists, physical therapists, chiropractors) 60 Take Home Points

Call your warfarin manager if you START, STOP or CHANGE ANY MEDICATIONS Experience any illnesses MISSED doses Schedule a procedure Be CONSISTENT with Vitamin K intake Alcohol consumption (Dont drink in excess) Physical activity 61 References

Holmes M, et al. The Role of Dietary Vitamin K in the Management of Oral Vitamin K Antagonists. Blood Reviews. 2012; 26: 1-14 Shibata Y, et al. Influence of Physical Activity on Warfarin Therapy. Thromb Haemost, 1998; 80: 203-4 National Institutes of Health http://www.ods.od.nih.gov/factsheets/cc/coumadin1pdf 62 Brigham and Womens Hospital Anticoagulation Management Service

Thank you! 63 Patient Advocacy Kathryn Mikkelsen Director, NATF Chair, NATF Patient Advocacy Committee September 20, 2014 Need PE, stroke, and ACS are the top three cardiovascular killers in the United States

Other 16.2% Disease of the Arteries 3.4% PE High Blood Pressure 7.8% Heart Failure 7.2%

Stroke Stroke 16.4% Coronary Heart Disease 49.0% MI Need NATF PAC Mission Statement

The goal of the North American Thrombosis Forum (NATF) Patient Advocacy Committee (PAC) is to provide education and advocacy in support of patients with heart disease and clotting disorders in alignment with NATF's vision to improve patient care, outcomes, and public health. PAC strives to bridge the gap in knowledge and understanding of these disease states so patients can make informed decisions about their health. Our membership is comprised of patients, healthcare professionals, and industry leaders with the mutual goal of improving patient outcomes through awareness and education. Committee Members

Current Initiatives Patient Resources Redevelopment Project Womens Health Initiative Minority Outreach Program Support Groups Speakers Bureau

Patient Resources Redevelopment Project Womens Health Initiative Minority Outreach Program Support Groups

Develop a micro-site on the NATF website specifically for women. Begin planning a live educational program Participate in community outreach events, such as health fairs, to promote the Womens Health Initiative Speakers Bureau Develop a micro-site on the NATF website specifically for women. Begin planning a live educational program Participate in community outreach events, such as health fairs, to promote the Womens Health Initiative

Conclusion NATF is a unique organization that brings together healthcare providers and patients. We are always looking for new members to join NATF and the PAC. We would be happy to work with you to host an educational event in your community. Visit the NATF website for reliable and up-to-date information. Need PE, stroke, and ACS are the top three

cardiovascular killers in the United States Other 16.2% Disease of the Arteries 3.4% PE High Blood Pressure 7.8% Heart Failure

7.2% Stroke Stroke 16.4% Coronary Heart Disease 49.0% MI Brigham and Womens Hospital Anticoagulation Management Service

Home Testing and Self Dosing David DeiCicchi, Pharm.D, CACP, RPh October 25th, 2014 Objectives Review different patient care models of anticoagulation management and supporting data Introduce patient home testing and self dosing: definition Describe our education and training sessions for

patients Discuss how you can begin home testing and self dosing Patient Care Models Routine Medical Care (Usual Care) Anticoagulation management by a physician or staff Typically without systematic policies and follow up Anticoagulation Management Service (AMS) Managed by personnel dedicated to anticoagulation with systematic policies in place to manage and dose patients

Patient Self Testing (PST): Home Testing Use of point of care monitor to measure INR at home Dose managed by usual care or AMS Patient Care Models Patient Self Management (PSM): Self dosing Testing your own INR and managing your own warfarin dose based on your result Van Walraven C et al. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129(5):1155. Home Testing

Patient self-testing is an alternative to traditional testing at a laboratory or physicians office You will be supplied with a point of care device and supplies to test your INR at home A small drop of blood from your finger is applied to a test strip and the machine will generate an INR within minutes BWH AMS will still manage your warfarin dosing Why test at home? Improves quality of life and independence Promotes active involvement in your healthcare Alternative for patients with poor venous access

More frequent monitoring leads to better control of your anticoagulation therapy May decrease clotting and bleeding events by increasing time spent in therapeutic range Disadvantages of Home Testing Potentially high cost of devices and test strips Difficulty performing the test Correlation with venipuncture varies from patient to patient Decreased accuracy with some disease states Antiphospholipid antibody syndrome

Are home monitors accurate? VP = 4.5 FS = 6.5 Home results correlate well with laboratory results Any observed difference is reproducible Accuracy decreases as the

INR increases What machines are available? ProTime INRatio 2 CoaguChek XS What are the differences?

* Only CoaguChek XS is insensitive to therapeutic doses of heparin/LMWH How do I get a home INR monitor? Discuss home testing with your warfarin manager Complete the online interactive training session and fill out an application AMS physician prescribes meter and testing supplies Monitor is delivered and training is scheduled within 2 4 weeks Education Session

Home Testing Process What is patient self dosing? PSM is the process of monitoring your anticoagulation which includes: Testing your own international normalized ratio (INR) with a point of care monitor Interpreting the blood result Managing your warfarin (Coumadin) dose based on your (INR) A medical facility trains the patient and oversees the quality of anticoagulation using active surveillance

Why self dose? Improves quality of life and further achieves independence Alternative for patients with limited time or laboratory access Eliminates time for provider to patient contact with dosing recommendations Promotes active involvement in your own health care PST With Or Without PSM Meta-analysis of 22

studies Compared to usual care > 8,400 patients Bloomfield et al. Annals of Internal Medicine. 2011;154:472-482. Limitations Self monitoring requires proper identification and education of suitable candidates 30-50% of patients chosen to self manage opted out or were not able to self manage

How do I begin self managing? You must be enrolled in BWH AMS Have a reliable mode of communication with AMS It is preferred that you utilize PST For at least 3 months time Discuss your candidacy with your warfarin manager PSM is not for everyone Sign up for a PSM workshop Receive self management training by an AMS clinician

PSM Workshop Dosing practice scenarios Documentation Recording INRs and dosing recommendations Identifying issues related to your anticoagulation Bleeding and clotting events Appropriate actions to take when an issue arises Reporting events and changes to AMS Present to the ED Example of Dosing Card

Dosing Card INR Action Less than 1.5 Call AMS 1.5 1.7 Increase 2 levels

1.8 1.9 Increase 1 level 2.0 3.0 Maintain level 3.1 3.5 Decrease 1 level 3.5 4.0

Decrease 2 levels Greater then 4.0 Call AMS Example of Dosing Card Dosing Card Level Dose

Example 1 35mg/wk 5mg daily 2 36mg/wk 6mg Mon and 5mg others

3 38mg/wk 6mg Mon Wed Fri; 5mg rest of week 4 40mg/wk 5mg Mon Fri; 6mg rest of week

5 42mg/wk 6mg daily 6 44mg/wk 7mg Mon Fri; 6mg rest of week 7

46mg/wk 6mg Mon Wed Fri; 7mg rest of week 8 48mg/wk 6mg Sun; 7mg rest of week 9

51mg/wk 8mg Mon Fri, 7mg rest of week Final Exam Once you have completed your workshop, you will be required to give 4 consecutive approved dosing recommendations prior to self managing. You will still need to:

report INRs to AMS be available if AMS has questions or concerns report any changes in your health or medications inform us of any suspected bleeding or clotting events Your Role In PSM You would be asked to: test your INR with a home machine at least twice a month and report all results adjust your warfarin dose using your dosing card document INRs and dosing report any major changes that can affect your

INR report bleeding or clotting events Our Role in PSM We are still fully responsible for your anticoagulation management Your warfarin manager will always practice active surveillance We are still available for any questions or dosing consults if needed AMS will continue to write prescriptions Summary

Patient home testing and self dosing is a safe alternative to warfarin management These patient care models can increase your time spent in your therapeutic range and decrease complications of anticoagulation therapy You can become more reliant on yourself and experience greater independence while on warfarin Become PRO-active in your warfarin therapy Brigham and Womens Hospital Main Anticoagulation Management Service

Thank you! Questions? Alternative Oral Anticoagulants Nicholas Feola, PharmD, CACP, RPh Brigham and Womens Hospital Anticoagulation Service Patient Seminar October 25, 2014 Objectives Discuss the benefits and challenges of warfarin

Identify the properties of ideal anticoagulants Compare the efficacy and safety of new oral anticoagulants (NOACs) with warfarin Choose the best anticoagulant based on specific patient characteristics What is an Anticoagulant? Anticoagulant Medication that affects the bloods ability to form a blood clot Stops an existing clot from becoming worse and prevents future clots from forming

Delay clotting time by targeting different enzymes within clotting cascade Types of Anticoagulants Oral Warfarin Rivaroxaban

Apixaban Edoxaban Dabigatran Intravenous Unfractionated heparin Bivalirudin Argatroban Subcutaneous

Unfractionated heparin Enoxaparin Daltaparin Fondaparinux Benefits of Warfarin Long track record First used in 1954 Proven efficacy Centralized

anticoagulation clinics Time in Therapeutic Range (TTR) >60% Rapid turnaround genetic testing Point-of-care testing Low cost Challenges with Warfarin Requires frequent monitoring due to: Narrow therapeutic window

Unpredictable pharmacology Multiple drugdrug and fooddrug interactions Increased risk of major and minor bleeds Properties of an Ideal Anticoagulant Properties Benefit Oral, once daily dosing

Ease of administration Rapid onset of action No need for overlapping injectable anticoagulant Minimal food or drug interactions Simplified dosing Predictable anticoagulant effect

No coagulation monitoring Extra renal clearance Safe in patients with renal disease Rapid offset of action Simplifies management in case of bleeding or intervention Antidote

For emergencies Eikelboom 2010 Properties of an Ideal Anticoagulant Properties Dabigatran (Pradaxa) Rivaroxaban (Xeralto)

Apixaban (Eliquis) Edoxaban (Savaysa) Oral, once daily dosing NO YES/NO (depends on

indication) NO YES Rapid onset of action YES YES

YES YES Minimal interactions YES YES YES

YES Predictable effect YES YES YES YES

Extra renal clearance NO NO NO NO Rapid offset of action

YES YES YES YES Antidote NO

NO NO NO FDA Approved Indications Indication Dabigatran (Pradaxa) Post-op Orthopedic

Prevention Treatment of Deep Vein Thrombosis (DVT) (2014) Rivaroxaban (Xeralto) Apixaban (Eliquis)

(2011) (2013) (2012) (2014) Treatment of Pulmonary

Embolism (PE) (2014) (2012) (2014) Non-Valvular Atrial Fibrillation

(2010) (2011) (2012) Prevention of recurrence DVT/PE

(2014) (2012) (2014) Edoxaban (Savaysa) Pending FDA

Approval Who Should NOT Use NOACs DO NOT use if you have a prosthetic heart valve Increased risk of thromboembolic and bleeding events with dabigatran Other medications not tested DO NOT use if you: Have severe kidney dysfunction Measuring Anticoagulant

Effect Not required for routine dose adjustment None of the current tests are suitable for quantifying anticoagulant effect Can determine if medication present Prior to emergency procedures In case of bleeding In case of potential drug interaction To verify compliance Options for Reversing Effects No specific antidote at this time Activated charcoal within 2-3 hours if

overdose General supportive care Fluids, PRBCs, local measures, surgical intervention Discontinue and allow effects to wear off Dialysis Various blood products How effective and safe are the NOACs compared to warfarin? Effectiveness: Stroke

Prevention Decrease incidence of strokes or embolic events with NOACs compared to warfarin Re-ly = dabigatran; Rocket-AF= rivaroxaban; Aristotle = apixaban; Engage AF = edoxaban Ruff 2014 Safety: Stroke Prevention Major Bleeding Decreased incidence of major bleeding events with NOACs

Higher incidence of Gastrointestinal bleeding with NOACs Re-ly = dabigatran; Rocket-AF= rivaroxaban; Aristotle = apixaban; Engage AF = edoxaban Ruff 2014 Efficacy: Treatment of DVT/PE Similar incidence of recurrent VTE, fatal PE or overall mortality with NOACs compared to warfarin Van der Hulle 2014

Safety: Treatment of DVT/PE Decreased incidence of major/fatal bleeding events with NOACs Similar incidence of Gastrointestinal bleeding with NOACs Van der Hulle 2014 Which Anticoagulant to Choose? Should be based on patient specific criteria Patient Characteristic

Anticoagulant Mechanical valve Warfarin Poor Compliance Warfarin Stroke while on warfarin Dabigatran or apixaban

Stable on warfarin Warfarin/consider switch to NOAC Kidney problems Warfarin Dyspepsia/GI upset Any except dabigatran

Recurrent GI bleeding Apixaban Once daily dosing Warfarin or Rivaroxaban Weitz 2012 Switching between Anticoagulants Always consult warfarin manager or

physician High risk for clotting and bleeding during transition Limit time without anticoagulation Limit overlapping effects Switching Between Anticoagulants Important to check INR result prior to switch INR

<2.0 Warfarin INR <3.0 INR <2.0 Dabigatran Rivaroxaban Apixaban

Limitations of NOACs No reversal agent Narrow scope compared to warfarin No long-term data Only 4-5years of information versus decades with warfarin Cost Higher co-pays for insurance Take Home Points Warfarin remains an effective treatment option, but

challenges include frequent monitoring and multiple interactions with drugs, disease states, and lifestyle The NOACs provide alternative anticoagulation options with minimal interactions and no need for laboratory monitoring The NOACs have equal or superior effectiveness compared with warfarin with a favorable safety profile Discuss with your physician if you will benefit from switching to NOAC References Eikelboom JW, Weitz JI. New Anticoagulants. Circulation 2010; 121: 1523-1532 Weitz JI, Gross PL. New Oral Anticoagulants: Which One Should my

Patient Use?. American Society of Hematology. 2012. 536-540 Ruff CT, Giugliano RP, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014; 383:955-962 Van der Hulle T, Kooiman P, et al. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost. 2014; 12:320-8 Brigham and Womens Hospital Main Anticoagulation Management Service Thank you!

Questions? FDA Approved Indications Indication Dabigatran (Pradaxa) Post-op Orthopedic Prevention Treatment of Deep Vein Thrombosis (DVT)

(2014) Rivaroxaban (Xeralto) Apixaban (Eliquis) (2011)

(2013) (2012) (2014) Treatment of Pulmonary Embolism (PE)

(2014) (2012) (2014) Non-Valvular Atrial Fibrillation (2010)

(2011) (2012) Prevention of recurrence DVT/PE (2014)

(2012) (2014) Edoxaban (Savaysa) Pending FDA Approval

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