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: θρόμβωσις) is the formation of a blood clot (thrombus; Greek: θρόμβος) 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

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

Upsetting the Balance • Stroke • Atherosclerosis: carotid artery plaques • Cardiac thrombosis – Congestive heart failure • Arterial thromboembolic events without obvious cause

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 • “Prophylaxis”—preventing 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 Women’s 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: Doctor’s office Outpatient lab VNA/Home draw services

Options for testing INR Point-of-care testing: Roche Coagu. Chek® XS INR system Alere INRatio® 2 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, 9 th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, ” Chest, 2012, 141(2 Suppl): e 44 -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, Mc. Ewan 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 review 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 Women’s Hospital Anticoagulation Management Service Living with Warfarin: What Affects your INR? Gina Dube, Pharm. D, 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 a“blood thinner” – Increasing the time it takes for blood clot

How Does Warfarin Work? § Blocks a process that uses Vitamin Kto make clotting factors, therefore reducing the body’s 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 (>500 mcg/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 don’t remember until the next day, call your warfarin manager. § DO NOT TAKE EXTRA DOSES TO CATCH UP 49

Alcohol § Alcohol interferes with the liver’s 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 warfarin dosage adjustment 57

Disease States and Warfarin § Increased effect § Decreased effect – Hyperthyroidism – Liver disease – Crohn’s disease – Congestive heart failure – Hypothyroidism – Fat malabsorption 58

Smoking and 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 (Don’t 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/coumadin 1 pdf 62

Brigham and Women’s 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 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 Women’s Health Initiative Minority Outreach Program Support Groups Speakers Bureau

Patient Resources Redevelopment Project

Women’s 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 Women’s 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 Women’s 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 16. 4% Coronary Heart Disease 49. 0% MI

Brigham and Women’s Hospital Anticoagulation Management Service Home Testing and Self Dosing David Dei. Cicchi, Pharm. D, CACP, RPh October 25 th, 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 physician’s 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? Pro. Time INRatio 2 Coagu. Chek XS

• Analysis time: 3 to 5 minutes • Test strips require refrigeration • Memory: 50 tests • Plug or rechargeable battery • Size: 9 x 4. 5 x 3 in. • Weight: 1. 6 lbs. • 15 µL blood sample • Analysis time: 1 minute • Test strips at room temperature • Memory: 120 tests • (4) AA batteries Coagu. Chek XS • 27 µL blood sample INRatio 2 PROtime What are the differences? • 8 µL blood sample • Analysis time: 1 minute or less • Test strips at room temperature • Memory: 100 tests • (4) AAA batteries • Size: 6 x 3 x 2 in. • Size: 5 x 3 x 1 in. • Weight: 9. 3 oz. with batteries • Weight: 4. 5 oz. without batteries * Only Coagu. Chek 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 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 Level Dose Example 1 35 mg/wk 5 mg daily 2 36 mg/wk 6 mg Mon and 5 mg others 3 38 mg/wk 6 mg Mon Wed Fri; 5 mg rest of week 4 40 mg/wk 5 mg Mon Fri; 6 mg rest of week 5 42 mg/wk 6 mg daily 6 44 mg/wk 7 mg Mon Fri; 6 mg rest of week 7 46 mg/wk 6 mg Mon Wed Fri; 7 mg rest of week 8 48 mg/wk 6 mg Sun; 7 mg rest of week 9 51 mg/wk 8 mg Mon Fri, 7 mg 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 Women’s Hospital Main Anticoagulation Management Service Thank you! Questions?

Alternative Oral Anticoagulants Nicholas Feola, Pharm. D, CACP, RPh Brigham and Women’s 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 blood’s 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 § Rapid turnaround genetic testing § Proven efficacy § Point-of-care testing § Centralized anticoagulation clinics § Low cost – Time in Therapeutic Range (TTR) >60%

Challenges with Warfarin § Requires frequent monitoring due to: – Narrow therapeutic window – Unpredictable pharmacology § Multiple drug–drug and food–drug 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 Minimal interactions YES YES Predictable effect YES YES Extra renal clearance NO NO Rapid offset of action YES YES Antidote 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 -5 years 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 Women’s 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