INR Magazine 2010 by wayne carley

y p o 0 C 1 t 0 n 2 e ti e a n P Ju

NR I Magazine

How are Doses of Warfarin Determined? David S. Shepro, MD & Jack E. Ansell, MD

! How to communicate more effectively next visit Getting Your Doctor to Listen

How Do Drugs Affect Coumadin ?

Interactions that could save you life

Self-testing: How Much Does it REALLY Cost? You will be surprised

Clots.....Patient Enemy #1

Information for prevention. A must for patients and their families.

NEW Studies: DNA

and

Warfarin

Are you taking Coumadin ? ÂŽ

If you are taking anticoagulants, did you know . . . s You can now self-test your PT/INR levels from home similar to the way people with diabetes self-test their blood glucose? s Most insurance plans now pay for self-testing if you are on long term anticoagulation for Atrial Fibrillation, Deep Venous Thrombosis (DVT), Pulmonary Embolism (PE) or have a Mechanical Heart Valve? The benefits of PT/INR self-testing: s &EWER TRIPS TO THE LAB OR CLINIC s &EWER NEEDLE STICKS s -ORE TIME IN RANGE AND LOWER RISK OF COMPLICATIONS1 s #ONVENIENCE OF TESTING WHENEVER YOU TRAVEL

Call today to learn more about self-testing 1-877-799-3126, or visit www.inrselftest.com Service available only by prescription.

Kortke H. Minami K. Breymann T. et al. INR self-management after mechanical heart valve replacement: ESCAT. Z Kardiol. 2001;90[6]118-124.

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Coumadin is a registered Trademark of Bristol-Myers Squibb

Philips Remote Cardiac Services 7 Waterside Crossing Windsor, CT 06095 Telephone: 877.729.8350

How PT/INR Self-Testing Works The PT/INR Self Test is similar to the test used by the millions of people who monitor their blood sugar every day, only with PT/INR you test once a week instead of every day. You’ll be given a meter, the supplies you’ll need to perform the test, and personal instruction on how to perform the test so you are completely comfortable doing it on your own, at home or wherever you travel. Simple. Here’s how easy it is to take the test, and how your doctor gets your results right away: 1. You obtain a drop of blood from a finger-prick and place it a test strip 2. The meter will analyze your blood and display your INR in about a minute 3. You call Philips’ toll-free phone number to report your INR results 4. Philips immediately sends a report to your doctor or clinic nurse, who can quickly contact you if your dose needs to be adjusted That’s all there is to it! Testing only takes a few minutes, and all you need is a phone to call in your results. Reliable. Meters have been fully approved for home use and have been extensively tested for accuracy and precision in measuring PT/INR anticoagulant levels in blood. Guaranteed. Because the meter is loaned to you for as long as you continue self-testing (no need to purchase one!), you never have to worry about a warranty expiring or the cost of making repairs. Philips will repair or replace your meter should that ever be needed.

To learn more about the benefits of INR self-testing, call 1-877-799-3126, or visit www.inrselftest.com Service available only by prescription.

Philips Remote Cardiac Services 7 Waterside Crossing Windsor, CT 06095 Telephone: 877.729.8350

Contents 5

How is Warfarin Dosing Determined?

Getting Your Doctor to Listen

Blood Clots While on Warfarin

This Issue Free for Patients

From our Families:

David S. Shepro, MD Jack E. Ansell, MD

Wayne Carley

Marie B. Walker Henry I. Bussey, Pharm.D., FCCP, FAHA

More Than Words Can Say By G.L. Rollins

INR Magazine is published by The Carley Group LLC www.inrmagazine.com

Drug / Supplement Interaction on Warfarin

DNA Testing and Warfarin

Heart Valves: Open and Shut

How Much does INR Testing Really Cost?

Diana M.. Schneider, Ph.D.

Byron St. James

The Patients Guide to Heart Valve Surgery Medtronic, Inc.

Philips Remote Cardiac Services / Wayne Carley

Reproduction of contents is prohibited without written permission.

Patients need to know... The contents of INR Magazine are for educational purposes only. Magazine content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or concern. NEVER disregard professional medical advice or delay seeking it because of something you have read in INR Magazine. INR Magazine does not recommend or endorse any specific tests, physicians, products, procedures, opinions, or other information mentioned in this publication. Reliance or actions taken on any information provided by INR Magazine is the sole responsibility of the reader.

How are doses of warfarin determined David S. Shepro, MD Jack E. Ansell, MD The ability of the blood to form clots is critical to human life, so that when a blood vessel is cut we donâ&#x20AC;&#x2122;t lose too much of our blood! In addition to forming blood clots, our bodies can limit bleeding by inciting the platelets (specialized cell fragments that circulate in the blood stream) to bunch up and form a plug for the blood vessel hole, and muscles in blood vessel walls can help to divert blood away from a bleeding vessel. A blood clot is a specialized thick, mucouslike substance that sticks to holes in our blood vessels and stops bleeding. There are some situations in life where an overabundance of clots form. When this happens serious complications can arise, especially when the clot obstructs blood flow in the legs, heart, brain, or lungs. The ability to control the generation of blood clots by affecting the production and/or function of these proteins provides effective and lifesaving therapy for many patients. Warfarin is a commonly prescribed medication that decreases the ability of the blood to form a clot.

The discovery of warfarin is interesting and enlightening. During the 1920s, scientists noted a bleeding tendency in cattle that had ingested moldy silage made from sweet clover. Scientists affiliated with the Wisconsin Alumni Research Foundation (WARF) identified and patented the active chemical agent. Only when a US Army inductee unsuccessfully attempted suicide with warfarin and fully recovered, did the investigation of the medicinal use of warfarin begin. Warfarin affects the role of Vitamin K, which is needed to make some of the proteins that contribute to blood clot formation. The structure of warfarin has a chemical resemblance to Vitamin K, but it is sufficiently different from Vitamin K, so that warfarin actually interferes with the action of Vitamin K. Blood clotting proteins formed in the presence of warfarin do not promote normal degrees of blood clot formation. Warfarin therapy must be administered in a manner that diminishes risk of the formation of dangerous clots and yet, allows for blood clots to form when needed to prevent bleeding. Warfarin has been shown to save lives and prevent dangerous life-altering blood clots. This drug can also lead to excess bleeding that can also be serious. Careful measurement and monitoring of the degree that blood clot formation is impaired by warfarin can maximize the benefits and minimize the risks. The ability of blood to clot can be measured in many ways. A commonly used assessment is the Prothrombin Time (PT). In this test, some blood is exposed to a biological

material (prothrombin time reagent) that promotes blood clot formation. The time it takes for a clot to form is measured and recorded as the PT. Since different companies make variations of this prothrombin time reagent, different prothrombin time reagents lead to slightly different PTs. In an effort to allow comparisons between different prothrombin time reagents and laboratories, we now use the International Normalized Ratio (INR) to assess the degree of diminished blood clot formation. The INR is calculated from the PT using a standardizing correction that compensates for the differences in prothrombin time reagents. Thus, we now simply use the INR to determine the degree that blood will clot in the presence of warfarin. Studies have established the appropriate “target” level of INR, along with minimum and maximum “range” of INR levels that are associated with improved clinical outcomes. For example the ultimate goal of warfarin anticoagulation in patients with atrial fibrillation is prevention of stroke and other clotrelated complications. These complications can arise if a clot forms in one of the chambers of the heart, and then breaks off from the main clot (embolize), is transported to an important artery (brain), blocks normal blood flow, and leads to a sometimes devastating stoke. The target therapeutic range of INR for most patients with atrial fibrillation is 2 – 3 with a target INR goal of 2.5. Other patients with different clot-forming conditions or patients with specific characteristics may be prescribed different INR targets and ranges by their doctor.

Since the range of INR levels that provide protection from stroke and limit the risk of bleeding is very limited, healthcare professionals note that warfarin has a narrow therapeutic range. The therapeutic range of warfarin is indeed very narrow when compared to other drugs. Warfarin is often cited for being one of the drugs that with the highest risk for complications. Thus, the careful management of this medication is vital.

CYP2C9 (Cytochrome P450 2C9) • Other medications that the patient might be taking especially the heart rhythm medication amiodarone, drugs that can increase the breakdown of warfarin, and certain antibiotics. • Overall nutritional status of the patient • Presence of liver disease or kidney disease • Vitamin K deficiency • Age, height, weight, race

Pharmacology As successive doses of warfarin are ingested and absorbed into the body, warfarin begins to accumulate in liver cells and causes levels of Vitamin K-dependent clotting factors to decline. At a certain point, a new and lower steady state concentration of Vitamin K-dependent clotting factors is reached. Depending on patient characteristics, it usually takes about 5 to 7 days for this new steady state concentration of Vitamin K-dependent clotting factors to be established. This is why it generally takes a few days to notice a change is the INR when warfarin doses are adjusted. Initiation of warfarin doses Choosing the best initial dose of warfarin is very important since the risk of bleeding related to warfarin appears to be highest during the first few weeks of warfarin therapy. There are several characteristics of patients that influence the initial doses of warfarin including: • the affinity of the main protein that warfarin targets (Vitamin K Oxide Reductase VKOR) • the main protein that metabolizes warfarin

There are 2 commonly utilized methods for initiation warfarin therapy. Whichever method is used, assessment of the INR response to the initial doses of warfarin is critically important to minimize the risks of bleeding. In many situations warfarin therapy is initiated while a patient is on some form of heparin. Many practitioners initiate warfarin therapy in otherwise healthy adults at a dose of approximately 5 mg per day. While higher “loading” doses are not recommended, very healthy outpatients may be treated with 10 mg (continued on page 11)

An astounding 142 million American adults, 66 percent of Americans, are overweight and 70 percent of Americans don’t get enough physical activity, blaming lack of time and motivation. The American Heart Association’s Start! movement aims to reverse the trend of physical inactivity in this country by encouraging people to walk. Walking can have a positive impact on a person’s overall health. Brisk walking for 30 minutes a day can reduce the risk of stroke, high cholesterol (LDL) levels and high blood pressure. It also has the lowest dropout rate of any type of exercise, largely because walking is free and easy to do. Studies show that adults may gain as many as two hours of life expectancy for each hour of regular, vigorous exercise. “Incorporating walking into your daily routine is one of the easiest changes you can make. You can hop off the bus or subway a stop or two earlier; you can take the stairs at work or park farther away,” said American Heart Association President Dr. Daniel Jones. “There are lots of little ways to incorporate a few more steps, which can truly have life-changing results.” According to the Centers for Disease Control, several risk factors surrounding coronary heart disease and stroke have been on the rise. Most alarming, the rate of physical inactivity has declined by only 2.5 percent since 1999. Inactivity makes a person 1.5 to 2.4 times more likely to have coronary heart disease. Start! focuses on four key elements to help combat the rising epidemic of inactivity:

1. MyStart! Online, a free, Web-based fitness and nutrition tracker, is the focal point for a walking program that offers constant, measurable personal improvement.

2. The Start! Fit-Friendly Companies recognition program officially recognizes employers who champion the health of their employees and work to create a culture of physical activity in the workplace. To be certified as “Fit-Friendly,” companies must implement a majority, if not all, of the wellness areas which include physical activity, nutrition and culture.

3. The Start! Walking Program encourages companies to promote walking at work and recognize and reward employees who move from a sedentary to a more active lifestyle. The program removes the significant barriers of lack of time and place for physical activity for millions of American workers.

4. The Start! Heart Walk, the American Heart Association’s premier fund-raiser, helps people improve their health by walking while helping fund the fight against heart disease and stroke. More than 450 Start! Heart Walks are held each year in cities nationwide.

Start! is sponsored nationally by SUBWAY® Restaurants, Healthy Choice® and AstraZeneca. For more information, call 1-800242-8721 or visit www.heart.org/start.

INR: International Normalized Ratio

A system established by the World Health Organization (WHO) and the International Committee on Thrombosis and Hemostasis for reporting the results of blood coagulation tests.

INR Magazine is designed for the INR patient, their physician, clinician and their families to better understand effective warfarin use and management. Improved communication with one another, familiarity with new self-testing INR devices, supplies, technology, vitamin K dietary considerations, management tools, and exercise are key components to accomplishing this understanding. Many of the nations leading authorities on warfarin management, technology and related medical conditions will be featured in these quarterly issues, keeping both physicians and their patients aware of the latest studies, innovations and educational opportunities available. Over 4 million Americans are currently on warfarin therapy. Nearly 400,000 are mechanical heart valve recipients, and that number continues to increase in the United States with new and safer innovations in management and technology. The emergence of patient self-testing and portable point-of-care (POC) INR devices has revolutionized the industry and welcomed the personal involvement of patients in their warfarin management. Historically, warfarin testing has been done with a venous draw at the lab, physicians office, or clinic as needed with test results often taking days. The risks of clotting, stroke and bleeding were an on-going concern for physicians and patients. INR Magazine is committed to the continuing education of the warfarin patient under the supervision of their personal physician, to maintain the highest level of health and safety during their warfarin therapy. Thank you for reading INR Magazine.

Wayne Carley Publisher

INR Magazine

Publisher

Wayne Carley

Literary Contributors

American Heart Association David S. Shepro, MD Jack E. Ansell, MD Henry I. Bussey Pharm.D., FCCP, FAHA Marie B. Walker, BBA Diana M.. Schneider, Ph.D. Philips Remote Cardiac Services

Subscriptions INR Magazine is provided at no cost to all physicians, clinicians and their patients upon request. Simply contact INR Magazine at:

free@inrmagazine.com We request that you provide postage to your practice by box. The Carley Group 6080 Lakeview Rd. Suite 2605 Warner Robins, Ga. 31088 478.319.7177 All rights reserved. The Carley Group LLC Copyright 2010

(continued from page 7)

per day for the first 2 days. It is appropriate to treat some patients with lower initial doses of warfarin, such as 2-2.5 mg per day. Characteristics of patients who should be considered for lower starting doses of warfarin include elderly, liver disease, presence of liver or kidney disease, small patients, patient on drugs with known INR-elevating interactions, and poorly nourished patients. Crowther reported a schema wherein doses on day 3 and beyond are guided by the INR response. For example patients who have a brisk response to warfarin will have lower subsequent doses of warfarin administered, whereas patients who have a delayed response to warfarin will require higher doses of warfarin. Central to this technique is the thoughtful interpretation of the day 3 â&#x20AC;&#x201C; day 6 INR response to the first doses of warfarin. Another technique used for the determining the initial doses of warfarin involves the analysis of the VORC and CYP genes. Certain variations of these genes are associated with more or less sensitivity to warfarin doses and the need for lower or higher doses. Algorithms that use these gene variations recommend a starting dose of warfarin. Some algorithms factor in additional patient characteristics that may further increase the accuracy of warfarin dose determination. One challenge with using genetic testing to predict initial doses of warfarin is that the results of testing may not be available in a timely manner for clinicians to use the data to make dosing decisions. Garcia notes that genetic testing cannot eliminate important hazards of warfarin

use such as fragmented transitions of care, concomitant antiplatelet therapy, and socioeconomic barriers to frequent INR measurement. Until definitive studies that compare various high quality techniques of warfarin initiation have been completed the best method for routine clinical practice is not currently known. Maintenance doses adjustments Once a patientâ&#x20AC;&#x2122;s INR has been successfully brought into the therapeutic range, regular assessment of INR is necessary for maximizing the safety of warfarin and to keep the INR in proper therapeutic range. While the genetic profile of a patient does not change over time, clinical characteristics of patients change regularly. These changes of diet, medications, liver function regularly affect the dose of warfarin necessary to keep the INR in the therapeutic range. Interestingly, in clinical practice some patients seem to have meaningful fluctuations in the INR that are often very difficult to explain and even more difficult to predict. When confronted with an INR that is out of the therapeutic range, practitioners need to analyze the degree that the INR is out of range and the causes of the out-of-range INR. If the degree of out-of-range INR is very minimal (ex. 0.1 units outside of range) then repeating the INR in several days may be recommended rather than make a dose change. If the degree of the out of range INR is significant, then the patient may be at risk for bleeding (high INR) or new clot formation (low INR). Given that bleeding can be severe and cause debilitating complications (continued on page 43)

Recent studies suggest that the average time you actually spend with your doctor may be as short as 7 minutes…..that is if you get to see your doctor. Many clinics and practices are relying on physician’s assistants or registered nurses to handle the increasing patient load of today’s medical clinic. In any case, your time is limited and you need to be prepared. The following are a few suggestions that may be helpful in maximizing your visit.

Be prepared. What do you need to know and take away from your visit today? During the weeks prior to your appointment, starting making a list of questions to ask. Don’t count on your memory, just write them down. It always helps to bring along a spouse or friend to help you listen to the answers, and it’s harder for the physician to walk away from two people asking questions. Prioritize. If you are in distress or in need of immediate attention from your physician or clinician, that of course is the highest priority of your appointment time. If this is a follow up or regularly scheduled visit, there is time to make the most of this opportunity. You have your list, so start at the top.

Why are you there today? This may seem obvious, but you need to focus your conversation on the task at hand. It’s very easy to become distracted by niceties or casual conversation you don’t have time for. Catching up on old times since your last visit needs to wait. 7 minutes is not very long. Mention up front that you have several questions that are important to you before you leave.

Take it. Don’t settle for the time you are given. Take the time you need. All too often, patients walk out of the office less than satisfied with their visit. As long as you keep asking relevant questions regarding your condition or course of treatment, in a polite and respectful manner, they will stay and interact. Their body language may suggest they have one foot out

the door, and mentally they might, but stick with it. Boldly ask your well thought out questions and expect a direct and satisfying answer. Yes, they are rushed and busy, but itâ&#x20AC;&#x2122;s your turn. There are waiting rooms full of patients wanting your treatment room. They would be happy if you would just leave and speed up the process. Speeding up the process is not your responsibility. Reducing waiting time is not your problem. Your warfarin therapy is your responsibility. Take charge of it.

Things to consider asking. A. Is my course of treatment as effective as it can be? Strides in warfarin management and testing are constantly in the news, so what used to be available may not be appropriate for you now. Within the last 10 years, management options for patients and clinics have changed dramatically. As hard as they try, warfarin clinics and cardiologists may not be aware of every new technology or improvement as it relates to patients taking warfarin. B. How do I manage my vitamin K intake? This is a tough question. Many medical schools do not require students to take classes in nutrition or dietary management. Thatâ&#x20AC;&#x2122;s a problem since vitamin K intake plays a huge role in proper warfarin dosing, weekly management and complications. Without addressing the vitamin K issue, staying within the proper INR range proves to be a struggle. C. Is self-testing something I can do? Your primary care giver has to answer this question. A prescription is needed to start your self-testing management. Not all patients taking warfarin suffer from the same conditions or risks of complications, so careful consideration must be given to this question. What is different about this topic is the speed with which warfarin management is changing. Hardly a week goes by that I donâ&#x20AC;&#x2122;t hear about a physician who had no idea that self-testing was so easy and covered by insurance. INR Magazine has been an eye opening periodical for many clinics and patients as technology, reimbursement and quality of care continue to improve.

D. How often should my INR be tested? Every patient is different of course, but testing is the only way to be certain of your INR reading. For years, patients were tested once a month or less. Complications such as internal bleeding and strokes were at all time highs, causing some to question the safety of warfarin. Until as recently the late 1990â&#x20AC;&#x2122;s, patients taking warfarin were suffering from every side effect imaginable. Key improvements in management were accurate, portable testing devices and insurance reimbursement. The combination of these two alone gave rise to improved patient care, dramatic reductions in strokes and bleeding events, reduced medical costs due to affordable prevention and a much higher quality of life for the warfarin user.

Much like diabetes self-testing that we all take for granted, INR self-testing has gone through and continues to struggle with acceptance within some medical communities, despite continued studies and overwhelming success in reducing strokes, bleeds and events in warfarin patients. A few years from now, self-testing may be the standard of care for all patients on warfarin therapy as technology progresses, costs continue to fall and insurance companies embrace this preventative care with greater coverage. Staying in therapeutic range as often as possible and as long as possible is the goal of every warfarin patient and their care giver. The tools are now available to make that a reality. The patient now has the power to take a greater role in management and responsibility. Talk to your doctors. They will listen. _____________________________________ INR

Blood Clots While on Warfarin (Coumadin ); R

Now What? Marie B. Walker Henry I. Bussey, Pharm.D., FCCP, FAHA www.clotcare.org

At ClotCare (www.clotcare.org), we often get asked if it is possible to get a new blood clot while taking warfarin (brand name Coumadin). The simple answer is yes. In order to understand the answer to this seemingly simple question, it is important to understand some background information about how warfarin and other anti-clotting medications work. Itâ&#x20AC;&#x2122;s also important to know what to expect if you get a blood clot while taking warfarin. How do anti-clotting medicines work? When a person is first diagnosed with a deep vein thrombosis (DVT) or pulmonary embolism (PE) blood clot, the recommended treatment includes receiving 2 types of anticlotting medications: (1) heparin, low molecular weight heparin, or a similarly acting agent (2) warfarin

Some names of low molecular weight heparins and heparin like medications that you may recognize include enoxaparin (Lovenox), dalteparin (Fragmin), and fondaparinux, (Arixtra).

These 2 types of anti-clotting medicines work differently. Heparin or heparin-like drugs are given to the patient to turn off the bodyâ&#x20AC;&#x2122;s clotting system. Warfarin is given to the patient to keep the clotting system turned off. Warfarin works to keep the clotting system from becoming reactivated. To reiterate, warfarin does NOT turn off the clotting system; rather, it keeps the clotting system turned off once it has been turned off by one of the heparin-like medicines. What might cause a new blood clot while on warfarin? There are a number of reasons why a person might get a blood clot while on warfarin. Some examples include: 1. Inappropriate initial treatment to turn off the clotting system 2. A low INR 3. A severe hypercoagulable condition 4. Introduction of an additional risk factor for clotting Inappropriate initial treatment to turn off the clotting system The American College of Chest Physicians publishes guidelines for the treatment of blood clots. The Chest guidelines are the

most widely followed recommendations for blood clot treatment in the USA. According to these guidelines, a blood clot should be treated with heparin or a similar drug for at least 5 days and until warfarin has been started and the INR is above 2.0 AND stable. The INR should be in the therapeutic range for 2 consecutive days to be considered “stable.”1

In order to keep the INR in range and prevent bleeding or clotting, the Chest guidelines recommend that patients on warfarin be managed by a specialized anticoagulation clinic. If no clinic is available, the Chest guidelines recommend patient self testing as the second choice and traditional medical care as the third choice option for anticoagulation care.1

If the patient does not receive an adequate dose of a heparin-like drug or if the heparin-like drug is not given for a long enough time, the patient may be at an increased risk of having another blood clot. For example, studies have shown that inadequate dosing of heparin during the first two days of treatment is associated with a 3 to 5 fold increase in the risk of having another blood clot.

A severe hypercoagulable condition

A low INR Well-managed warfarin is very effective at preventing new or growing blood clots. Well-managed means that the INR is kept within the target range. The usual target range is 2.0-3.0, but this range will vary depending on the reason warfarin is being used. The INR basically tells the anticoagulation clinician if the patient is getting too little, too much, or just the right amount of warfarin. If the patient is getting too much warfarin, then the INR goes up. As the INR increases, the patient’s risk of bleeding increases. If the patient is getting too little warfarin, then the INR goes down. As the INR decreases, the patient’s risk of developing a new blood clot increases. The lower the INR goes, the greater the risk of forming a new blood clot.

A hypercoagulable condition is a biochemical abnormality that increases the risk of blood clot formation. There are a number of hypercoagulable conditions. These conditions are sometimes referred to as blood clotting disorders. Some hypercoagulable conditions increase the risk of clot formation a little; other hypercoagulable conditions increase clotting risk a lot. The conditions that increase clotting risk significantly are known as strong hypercoagulable conditions. Patients with a strong hypercoagulable condition, such as antiphospholipid antibody syndrome, may be more likely to get a clot with a slight drop in the INR than a normal patient without such a condition. In such patients, the clinician may choose to set a slightly higher target INR. Introduction of an additional risk factor for clotting The usual target INR of 2.0 to 3.0 may indicate a level of anticoagulation with warfarin that should prevent another clot most of the

time, but a clot may develop if an additional risk factor or reason for clotting is introduced. For example, trauma and cancer are two factors that can promote clotting. Therefore, if a patient on warfarin has a significant injury or develops cancer, then he/she may need a higher dose of warfarin to achieve the same level of clotting protection as before the injury or cancer occurred. If such risk factors develop, the clinician may choose to increase the target INR or change to an alternative anti-clotting drug such as low molecular weight heparin. What treatment should I receive if I get a new blood clot while taking warfarin? Warfarin does NOT turn off the body’s clotting system. Rather, warfarin keeps the body’s clotting system from becoming active. If you get a new blood clot while taking warfarin, then you know that your body’s clotting system has become active despite the protection offered by warfarin. Since the body’s clotting system has become active, you need medicine to turn off the clotting system. So, if you have a clot while on warfarin, you need a heparin-like drug for at least 5 days and until warfarin has gotten the INR above 2.0 and stable. If a new clot develops while on warfarin, the initial treatment for the new clot is exactly the same as it was for the initial treatment of the first clot. Warfarin may still be used to keep the clotting system turned off after the heparin-like medication has turned off the clotting process. For patients who develop a clot while taking warfarin, the INR target may be increased and the planned duration of warfarin therapy will likely be extended to life-long. What can I do to minimize my risk? There are a number of things you can do to minimize your risk of getting a blood clot while on warfarin. You can take control of your health care and minimize your risks by: - Taking your warfarin according to your doctor’s instructions - Maintaining a healthy, consistent diet - Avoiding factors that are known to increase the risk of blood clots (such factors include injury, immobility that may result from sitting for prolonged periods, obesity, smoking, etc.) - Talking to your doctor about any changes in diet, supplement use, medication use, exercise level, alcohol consumption, smoking, lifestyle, etc. - Having your INR checked regularly according to your doctor’s instructions and ensuring that both you and your doctor know your INR results - Watching for signs and symptoms of new clotting such as leg swelling, leg warmth or red ness, leg pain, difficultly breathing, or chest pain - Seeking medical attention immediately if you suspect that you may have a new blood clot or are going to be exposed to additional clotting risk factors References 1.Ansell J., Hirsh J., Hylek E, et. al. Pharmacology and Management of the Vitamin K Antagonists:American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest June 2008 133:160S-198S; doi:10.1378/chest.08-0670. http://chestjournal.chestpubs.org/content/133/6_suppl/160S.full

INR Magazine

INR Magazine is provided at no cost to all of your patients through your clinic or practice.

Physicians and Clinicians wishing to request copies of INR Magazine for their practice, clinic and patients may do so by contacting INR Magazine at:

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478.319.7177 We ask that you provide postage costs to your clinic. We have no wish to contact your patients. Patients wishing to receive copies of the magazine are requested to inquire at your physicians office or warfarin clinic. INR Magazine is provided at no cost other than postage. Thank you for your interest in INR Magazine and your support of patient education. INR Magazine Wayne Carley 6080 Lakeview Road Suite 2605 Warner Robins, Ga. 31088 478.319.7177

“More Than Words Can Say” by G.L. Rollins

Safe, comfortable, economical and accurate. Just a few of the words used to describe the self-testing experience of patients using home testing monitors as part of their warfarin therapy. “ Greater independence. That’s what I experience everyday now. I’ve had my monitor for about 4 months and I’ve become so confident in my ability to test and manage my therapy that my husband and I are traveling again. We recently visited our children and grandchildren in Ohio. We hadn’t seen them in more than 4 years. I never felt safe being away from my clinic or away from home.....in case something were to happen to my INR. My husband helps me check my levels weekly and calls them in to my clinic for me. I’m in range all the time now. I really feel good.” Sally and Bruce C. Youngsville, Pa.

Self-testing for warfarin patients is a relatively new technology Many physicians are still unaware of its availability to patients and the accuracy of the meters. Much like Diabeties testing, it will take time and education to get

the word out. As more and more patients show improvement and success taking a more active role in their warfarin management, doctors too are becoming more comfortable prescribing

“It’s really been a godsend” self-testing for their patients. Numbers don’t lie, and as the incidents of adverse events within the self-testing community continue to plunge, this technology is well on its way to becoming the rule for warfarin therapy rather than the exception. “It’s hard to get around lately. I don’t drive anymore so I had to depend on my daughter to take me to the clinic to have my INR checked. I was usually in range, but was always scared that I wasn’t. Sometimes I would feel under the weather and wonder if my INR was off. The fears of clots was real and I hated being afraid of that. Last year, my daughter heard about a self-testing monitor and made some calls. When we visited the clinic, I asked about it and showed them the information my daughter printed out. They were aware of the devices and asked

What People Are Saying About PT/INR Self-Testing Thousands of people are successfully testing their PT/INR levels with their own INR self-testing meter at home, or when they travel. Here are just a few of the stories weâ&#x20AC;&#x2122;ve received about what they like about self-testing. â&#x20AC;&#x153;Once I was actually walking around with an INR of 26 and didnâ&#x20AC;&#x2122;t know it. If Iâ&#x20AC;&#x2122;d had this testing system, I would have known to get medical help right away.â&#x20AC;? â&#x20AC;&#x153;Now I donâ&#x20AC;&#x2122;t have to wait in a doctorâ&#x20AC;&#x2122;s office. I donâ&#x20AC;&#x2122;t have to wait for results. The results are immediate. There have definitely been fewer complications as a result of the self-testing. And my health insurance understands that it is better than going to a lab once a month, so they pay for my meter and all my supplies.â&#x20AC;? â&#x20AC;&#x153;I was nervous at first, but once I learned how to do the self-test, I canâ&#x20AC;&#x2122;t imagine going back to the lab. It is such a time saver and I get the results right away instead of driving to a lab. The home test gives me control over my life -- it really does!â&#x20AC;? â&#x20AC;&#x153;I cannot imagine my life without self-testing. I travel a lot and no matter where I am, I can test and call in my results to Philips and they immediately contact my nurse to see if my Coumadin levels have to be adjusted.â&#x20AC;? We are Philips, a global leader in medical technology and services. Our goal is to simplify healthcare. /UR 04 ).2 SELF TESTING SERVICE NOW MAKES IT EASIER FOR PEOPLE TO LIVE WITH #OUMADIN OFFERING MORE convenience, greater peace of mind and a better quality of life. The following conditions have been approved by Medicare and most commercial heath plans for INR self-testing: s #HRONIC !TRIAL &IBRILLATION s -ECHANICAL (EART 6ALVE s $EEP 6EIN 4HROMBOSIS s 0ULMONARY %MBOLISM s (YPERCOAGULABLE 3TATE

To learn more about our INR self-testing service, call 1-877-799-3126, or visit www.inrselftest.com Service available only by prescription.

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me if I would like to give it a try. My daughter promised to help me with it, so I said yes and got a prescription for self-testing. It’s been wonderful. My daughter comes over every week to help me test and I get the results in a few minutes. Some of the other advantages are my arm isn’t sore or bruised anymore from them drawing blood. The finger stick is a big improvement. Plus, we don’t have to make the 45 minute drive to the hospital. Sometimes the weather is bad and I worry about my daughter having to drive in it. Overall, I think this was a great decision for me. I’m very pleased with how it has improved my life and state of mind. It’s really been a godsend.” Sara F. Chicago Ill. Self-testing is not for all patients. You and your doctor should decide if it would improve your time in range and quality of life. The studies are conclusive that warfarin management using a self-testing device can have a dramatic impact on both. Each patients situation is a little different. Age, specific condition, availability of family and friends, geographic location, ability to travel.....all are considerations that need to be evaluated before making any decision. “ I have been self-testing for 9 years now. My 2 heart valves were put in because of my heart murmurs. My husband and I have traveled most of our married life and I was not about to give that up. I haven’t been testing at the clinic in forever, because I seem to stay in range about 99% of

the time. My doctor loves my success and so do my husband and I. I feel good, I can sleep at night and I don’t worry anymore about my numbers. Checking every week has become common place like going to the grocery.

“..in range about 99% of the time..” We are planning another cruise next month. I can’t wait.” Alice and Tim Corpus Christy, TX. (continued on page 24)

Standing Stone and Philips Healthcare Announce a Simple Solution for INR Patient Self-Testing (PST) A new Standing Stone system enhancement makes it easier to manage PST patients. Now your Philips PST patientsâ&#x20AC;&#x2122; test results can automatically appear in your Standing Stone system, just minutes after they take their test. Home Tester

Benefits for your clinic: s +EEP CONTROL OF !,, YOUR ANTICOAGULATION PATIENTS â&#x20AC;&#x201C; PST and in-clinic results instantly available. â&#x20AC;&#x201C; Dosing and follow up information at your fingertips. â&#x20AC;&#x201C; Automated critical value alerts from your INR@Home patients.

0HILIPS ).2 (OME

s %FlCIENCY OF #LINIC 7ORKmOW â&#x20AC;&#x201C; Avoid unnecessary faxes or phone calls. â&#x20AC;&#x201C; Eliminate time spent entering PST results. s #ONTINUITY OF 0ATIENT -ANAGEMENT â&#x20AC;&#x201C; Stay on top of every INR. â&#x20AC;&#x201C; PST results instantly flow to your desktop.

9OUR #LINIC S 3TANDING 3TONE 3YSTEM

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For patients wanting to manage their warfarin therapy more closely, that is now possible with the support of your physician. The service provider for your self-testing supplies will work directly with your care provider to track your progress, keep you in range longer and answer all of your questions. Complete confidence is only a phone call away. “ I have not been comfortable with learning new technology. I still use a typewriter and send letters to family and friends. A friend of mine at church is on warfarin too, and told me about her new meter where she tests from home every week and calls in the results to her clinic. She loves it. I told her I didn’t think I could handle the responsibility... ....what if I made a mistake? She said that they train you over the phone and in person until you’re comfortable doing it. There is also phone support everyday if I have questions or

need help. My doctor said that she would also keep a close eye on me and that I should try it. My husband said he would help me too and we could do it together. I think I’m going to give this a try. If it means staying healthy and reducing my risks for complications, it’s worth it. Who knows....maybe I’ll love it too.” Rebecca T. Miami, Fl. _________________________________ INR

How Do Drugs and Supplements Affect Coumadin or Warfarin Levels? Diana M.. Schneider, Ph.D.

Excerpted from The Coumadin® (Warfarin) Help Book, , DiaMedica Publishing, 2008©, New York

Many factors can affect the way your body responds to anticoagulant therapy. Managing your dose of Coumadin® or warfarin is complicated by the fact that they interact with many commonly used medications. Interactions with a wide range of drugs is second only to the vitamin K content of your diet in terms of their potential to cause problems in maintaining your INR in the desired range, and your medications need to be monitored closely. Drugs that you take every day can be easily compensated for in your daily dose of Coumadin® or warfarin. This includes medications such as those you take for high blood pressure, thyroid problems, or diseases such as diabetes. The problems arise with drugs you may need to take on a shortterm basis, such as antibiotics for an infection. A short-term need for a new medication may require more frequent INR level measurements during its use, so that the dosage of anticoagulant can be modified as needed.

Most commonly used drugs that affect the INR do so because they are metabolized in the liver—broken down into small molecules that can easily be excreted by the kidneys or bladder—by the same enzymes that metabolize Coumadin or warfarin. When these enzymes are actively involved in metabolizing other drugs, they are less able to metabolize the anticoagulant—essentially they

“compete” for the enzymes’ attention. By slowing degradation of the anticoagulant drug, these interactions increase in the amount of anticoagulant medication in the body, and thus slow the rate of clotting and increase the INR—sometimes into the range in which the risk of a bleeding episode is seriously increased.

“...it increases the INR.” Some drugs, especially antibiotics, also decrease the level of bacteria in the gut. Some of these bacteria make vitamin K2, and the loss of this vitamin has the same result as eating too little vitamin Kcontaining foods; it increases the INR. Other drugs decrease clotting because they inhibit the function of platelets, irregularly-shaped, colorless bodies that are present in blood and whose “sticky” surface lets them, along with other substances, form clots to stop bleeding. It is important to realize that impaired platelet function is not reflected in the INR, and the increased risk of bleeding will not likely be detected with normal monitoring. This makes it especially important that you work with your health care provider to achieve relief of symptoms safely.

A number of websites have detailed information about potential interactions with drugs, including http://www.coumadin.com and generic/warfarin_ad.htm. The following summarizes some of the main drug types that can affect the INR.

Commonly Used Medications That Can Alter the Effects of Oral Anticoagulants on the INR. - Nonsteroidal Anti-inflammatory Drugs Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation due to arthritis and other conditions. These drugs affect platelet function and significantly increase the risk of gastrointestinal bleeding in people on anticoagulant therapy. This combination is at the top of the list of the ten most dangerous drug interactions, and it is partially responsible for the Black-Box Warning associated with Coumadin and warfarin, meaning that the drug is associated with a significant risk of serious or even life-threatening adverse effects. These drugs include aspirin, ibuprofen (Motrin®), naproxen (Aleve®, Naprosyn®), and many others. Of these, aspirin is the most important because of its widespread use and prolonged effect. Any drug prescribed to reduce inflammation, pain, and fever falls into this category, so you should check with your doctor before

taking them. Acetaminophen (Tylenol®) has less of an interaction than other drugs in this group, so it is often suggested as the first choice for pain. Be aware that acetaminophen can be a dangerous and even fatal drug when taken in excess over a prolonged period of time, which can easily occur if it is combined with other acetaminophen-containing medications such as cold preparations. Your physician might prescribe a mild narcotic or other medication as an alternative for managing pain. - Cox-2 Inhibitors The group of pain and anti-inflammatory medications known as cox-2–specific inhibitors, such as Celebrex®, is considered NSAIDs, but these drugs have only a minimal effect on platelet function and can may be associated with less gastrointestinal bleeding in people who require anticoagulants. However, Celebrex can cause increases in INR and bleeding events. More frequent INR testing is recommended to make sure that any interactions are caught early, and to avoid or greatly minimize the potential for a bleeding event. People who need a Cox-2 medication are often stabilized, but on a lower dose of anticoagulant medication than they previously required.

One of the most important groups of drugs that can affect clotting includes many commonly used antibiotics and sulfa drugs. They reduce the metabolism of Coumadin and warfarin, and can greatly increase the effect of your anticoagulant medication. This has the same effect as decreasing vitamin K in the diet—they increase the effect of anticoagulants as reflected by an increase in the INR, and increase the potential of a bleeding episode. Whenever you are prescribed a drug to treat an infection of any kind, be sure the physician prescribing it knows that you are taking an oral anticoagulant, and contact your Coumadin/warfarin provider to discuss whether the dosage should be modified, and whether more frequent INR testing is appropriate. This group of drugs includes (but is not limited to) Bactrim®, Biaxin®, Cipro®, erythromycin (and other antibiotics whose name ends in “mycin”), the broad-spectrum penicillins, and the tetracyclines. As noted above, some antibiotics also reduce the number of bacteria in the bowel, which make significant quantities of vitamin K2. A wide variety of commonly used antibiotics and sulfa drugs will require a reduction in your anticoagulant dose by as much as 50 percent. These drugs also cause among the most serious drug interactions and are

Drugs and Supplements

-Antibiotics

Essential reading for anyone taking Coumadin® or warfarin, with the information your patients need to successfully manage their medications and minimize adverse events.

NEW!

The Coumadin® (Warfarin) Help Book Anticoagulation Therapy to Prevent and Manage Strokes, Heart Attacks, and Other Vascular Conditions Diana M. Schneider, Ph.D. “…this highly readable, reassuring little book provides me and all its users the confidence to simply stop worrying, take a deep breath, and get on with your life…” — Maggie Lichtenberg, author of The Open Heart Companion

“…a quick read; packed with vital information, [it] should be a part of prescribed care for all Coumadin® (warfarin) patients.” — Cleo Hutton, author of After a Stroke: 300 Tips for Making Life Easier

“… a comprehensive and thoroughly ‘user friendly’ guide...” — Midwest Book Review

“…read from cover to cover or use as a valuable resource when questions surface… If you or your loved one is told to take Coumadin® or warfarin, (this book) is essential for your understanding.” — Reader Views “…If you take Coumadin® (or the generic form) you need this book!!!” — Amazon.com Reviewer

The Coumadin® (Warfarin) Help Book is essential reading for anyone taking the anticoagulant drug Coumadin® or its generic form warfarin-especially if they find the dietary and medication guidelines confusing or complicated. Emphasizing that consistency is the key to success, the Help Book explains why these drugs require both dietary modifications and careful monitoring of both prescription and over-the-counter medications.

TO ORDER

In this book your patients will learn: • how Coumadin® and warfarin act to prevent the formation of blood clots that can cause strokes, heart attacks, or pulmonary embolisms; • why the level of these drugs must be maintained within a very narrow range; • the potential side effects of anticoagulant therapy, including the risk of bleeding when appropriate levels are not maintained as well as "nuisance" effects such as mild hair loss; • what they should know about the vitamin K content of foods, and how to regulate their diet to maintain clotting at the optimal effective level; • how both prescription and nonprescription drugs, as well as alcohol, can affect anticoagulant effectiveness, and how patients can work with their health care providers to maintain an optimal anticoagulant level while taking needed medications; • how coagulation therapy may be managed when they need surgery or are diagnosed with new medical conditions.

CONTENTS: Introduction. From the Author: How to Use This Book: General Guidelines for Successfully Managing Coumadin® and Warfarin. The Basics: Why Anticoagulation Is Necessary. What Is an Anticoagulant, and Why Is Controlling Blood Clotting So Important?; The Consequences of Abnormal Clot Formation: Stroke, Heart Attacks, and More; Common Conditions That Cause Blood Clots to Form. Successful Anticoagulation Management. How Should I Take Coumadin® or Warfarin?; Monitoring: Maintaining Your Clotting Rate in the Desired Range; Side Effects of Oral Anticoagulant Therapy; Dietary Considerations with Oral Anticoagulant Therapy; How Do Drugs and Supplements Affect Coumadin® or Warfarin Levels?; Anticoagulants and Other Medical Conditions. General Health Concerns. Managing Your General Health; Out and About: Managing Coumadin® or Warfarin Away From Home. Resources. Diana M. Schneider, Ph.D. is a biochemist and health publisher. She wrote this book following her own experience with taking Coumadin®, when she found that there was no single source of information about the drug and the need to balance diet and exercise, exercise care when taking other medications, or deal with side effects. She decided to base this book in her own experience to make it possible for anyone needing anticoagulation medication to live a normal, healthy life with minimal restrictions.

All DiaMedica publications are available at online bookstores, including Amazon.com and Barnesandnoble.com, as well as in your local bookstores. You can also visit our website at www.diamedicapub.com. If you would like to consider purchasing multiple copies of this book for use in your clinic setting or for courses or counseling programs, please contact us for review copies, a brochure written for patients, and for bulk pricing information.

ISBN: 978-0-9793564-2-1 • Softcover • 112 pages • $14.95

DiaMedica Publishing 150 East 61st Street, New York, NY 10065 Phone: 212-752-2098 Email: info@diamedicapub.com Web: www.diamedicapub.com

another reason for the Black Box Warning that comes with Coumadin and warfarin prescriptions.

This can increase bleeding time as reflected by the INR. When you have a cold or the flu, you should have an INR test as soon as you are well enough to do so.

- Other Drugs Other kinds of drug known to interact with oral anticoagulants include antiepileptic medications, hormones such as Synthroid® or generic levothyroxine, and some antidepressants. If taken on a daily basis, these medications can be easily adjusted for over time. A very few drugs can increase the rate of elimination of Coumadin and warfarin, causing the INR to decrease and reducing the effectiveness of the anticoagulants. The main drugs that have been identified as having this effect are used to reduce cholesterol and other fatty substances in the blood; they include Cholestyramine® and Colestipol®.

Most cold and flu medications contain acetaminophen (Tylenol) and other drugs to ease symptoms. It is important not to take them excessively. Be especially careful of cough drops containing zinc, which affects Coumadin and warfarin uptake from the digestive tract and can lower the INR.

- Alcohol Abuse Alcohol use affects the metabolism of anticoagulant medications and can elevate the INR. It is important that you not use alcohol to excess while taking an oral anticoagulant.

- Cold and Flu Medications

Some physicians recommend not having any alcohol while on anticoagulation therapy, while others—like my own Coumadin/warfarin clinic—recommend that your alcohol intake should not exceed two drinks per day. Like medications and vitamin K-containing foods, consistency is the key. It is easier to adjust your dose of oral anticoagulant if you drink moderate amounts of alcohol regularly than if you use it irregularly, especially if you indulge in binge drinking.

As noted earlier, colds and flu can alter your overall metabolism and affect the way Coumadin or warfarin is handled in the body.

People who have liver damage or who abuse alcohol may need to be treated with heparin injections instead of an oral anticoagulant.

The “bottom line” is to check with the health care provider responsible for your overall care before taking any new medication. She will consider potential drug interactions before prescribing any new drugs, and will also carefully monitor medications prescribed by other physicians.

(continued of page 30)

Interactions with Herbal Preparations The increased popularity of herbal remedies and complementary and alternative medicine (CAM) has created a growing number of concerns about their possible interactions with anticoagulants. Some herbal remedies appear to have the potential to enhance or decrease the action of anticoagulants, and some of them actually have anticoagulant properties. In either case, they have the potential to significantly alter the effects of your medication. For this reason, it is very important to discuss with your physician or nurse any herbal products that you use. At my Coumadin/warfarin clinic, starting, stopping, or changing herbal medications is one of the major reasons why INR fluctuations occur.

These herbal agents include (but are not limited to): • Ginkgo (or Ginkgo Biloba) is used to increase brain blood flow, prevent dementia, and improve memory. • Ginseng is used to help with fatigue and weakness; in addition to its effect on the INR, it can increase blood pressure and heart rate. • Garlic (as a supplement, not in the diet) is commonly used to help lower high cholesterol levels, high triglycerides, and high blood pressure. • Ginger is commonly used to relieve nausea and poor digestion. It increases the risk of bleeding by inhibiting platelet aggregation. A few herbal products, such as St. John’s

As with medications, you can take most herbal preparations while on Coumadin or warfarin, but you need to take them consistently. It is especially important to remember that herbal preparations are not required to be standardized, and that potency can vary significantly from one lot to another. Because of this, look for a brand that claims to be standardized, and use that brand consistently. Most herbal preparations known to interfere with oral anticoagulant therapy increase the INR and risk of bleeding. Some of them contain coumarins, which are similar to Coumadin products without first asking your doctor. Some of them affect platelet aggregation, and their effects will not be seen in the INR, which can make them of particular concern.

Wort (used to help with mild to moderate depression) and coenzyme Q10, have the opposite effect and decrease the INR. Summary: Many medications and herbal preparations can affect the INR, especially those that either or metabolized by the same liver enzymes that are involved in metabolizing Coumadin or warfarin. They can almost always be managed successfully provided that your health care providers are all aware that you are taking oral anticoagulant medication, but it may be necessary to obtain more frequent INR measurements while taking drugs on a short-term basis. _________________________________ INR

Updates from the National Blood Clot Alliance (NBCA) By Tom Hogan, Secretary

Several important milestones in the growth of the National Blood Clot Alliance (NBCA) are taking place in 2010 which will help us reach out further to the patients and members of the general public then we have in the past and to make our name that much more recognizable for those looking for answers to their health concerns. NATT’s NEW NAME. The National Alliance for Thrombosis and Thrombophilia (NATT) has changed its name to the National Blood Clot Alliance (NBCA). The new name was officially launched on March 9, 2010 at the opening plenary of the National Conference on Blood Disorders in Public Health in Atlanta, Georgia. Elizabeth Varga (co-founder and board member of the National Blood Clot Alliance) and CEO Alan Brownstein announced the name change. The new name reflects the importance of keeping public health messages as simple as possible. SOCIAL NETWORKING: In February of 2010, NBCA launched its first social networking initiative on Facebook. Within only a couple of weeks our fan base had grown from 10 people to almost 700 fans from not only around the nation but also Canada and the United Kingdom. We hope through this Stop the Clot Facebook page we can extend not only our visibility but also bring information about blood clots and clotting disorders to patients looking for information. The Facebook page is moderated by NBCA Board and Committee members. We will continuously try to provide answers to patient questions that they may not be receiving through their primary care physician. On YouTube, you can find video segments from our Minneapolis Stop the Clot Seminar. We hope by providing this information that patients who cannot attend one of seminars can receive the same educational benefits from viewing one of our seminars on line. Another video found on our YouTube site discusses the importance of anticoagulants during knee and hip replacement. Podcasts from our YouTube videos are also available. Our YouTube, Podcast, and Facebook websites can be found at our web page at www.stoptheclot.org

ATHLETE PROGRAM: Another important addition for our organization this year is our Athlete Program. The National Blood Clot Alliance has created a way for individuals or teams to help increase awareness through our Stop the Clot® network of athletes. The program will recruit runners, walkers, cyclists, and tri-athletes to join NBCA in bringing its Stop the Clot® message to increased numbers of Americans. Roland Varga, a triathlete from Columbus, Ohio, created the idea of an awareness program as he ran in marathons and competed in triathlons. “I wore a Clot Buster shirt, covered with red polka dots,” explained Varga, “and got a lot of attention! I also gave out a lot of information. If I could do this, we could multiply by hundreds if we recruited others to work with us.” Known as “Clot Buster” to many friends and associates, Varga continues his goals of raising awareness and funds as he competes in events in the Midwest and other parts of the country. “Several hundred thousand Americans die each year from blood clots in their veins,” explained Alan Brownstein, NBCA Executive Director. “And we know that most of these lives could have been saved if more patients and health professionals had known about risks, symptoms and treatments. Our new program, which we call ‘Stop the Clot’ right now will bring this message of help and hope to many and will allow us to expand our awareness, prevention, treatment and support mission on behalf of many more.” People interested in participating in a marathon, half marathon, 5k, walk, cycling event, Ironman or triathlon event to support NBCA’s mission and programs are asked to contact NBCA by calling 1.877. 4 NO CLOT, e-mailing Judi Elkin at jelkin@stoptheclot. org or by visiting: http://www.stoptheclot.org/events/ natt_fund_raiser.html.

Byron St. James

More than 2 million new patients begin warfarin therapy every year. Although the most commonly prescribed drug for those at risk of blood clots from atrial fibrillation (a type of abnormal heart beat), strokes, deep venous thrombosis (DVT), pulmonary embolism, or those who have received heart valve replacements, correct dosing remains an obstacle. Warfarin and the brand name Coumadin are commonly referred to as blood thinners, when actually they are not. To put it simply, warfarin interacts with vitamin K in the blood to determine how quickly the blood coagulates, or clots. Each person is different physiologically making warfarin a difficult drug to prescribe. The right dose varies greatly from person to person, and the consequences of under or over-dosing can be significant. Too little warfarin puts the person at increased risk of forming blood clots and having a stroke; too much

warfarin puts the person at risk for a potentially life-threatening bleeding event—bleeds in the gastro-intestinal track and brain are the most common.

Is warfarin dangerous? Because of the complexity of warfarin dosing and the volume of patients taking it, statistics on warfarin related death and complications give the impression that it is dangerous. That couldn’t be further from the truth. Any drug can be dangerous when prescribed in the wrong dose, but with new and accurate testing procedures available to patients, warfarin can be amazingly safe. Patients who self dose, don’t test regularly or ignore their physician’s instructions put themselves at risk for the possible complications listed above. The fact is, warfarin, when managed correctly, saves lives……lots of them.

What is the right dose of warfarin for me? A variety of factors influence how much warfarin each patient needs, including age, sex, weight, daily diet and now….. genetics. Initial dosing of warfarin for any patient is an approximation. Approximations can be risky. Doctors choose what seems to be the best dose, then test the patient for the next several weeks, adjusting the warfarin dose until the test results show that the patient’s blood is properly clotting. It may take weeks to determine the right dose and the while the patient remains at risk of complications or even death. The highest risk of warfarin complications occurs during the first 30 to 60 days

after beginning warfarin therapy. There are a lot of reasons. We are learning that some of the variation stems from individual differences in the enzymes that metabolize warfarin (enzymes that break warfarin down and destroy its anticoagulant activity). Some people have enzymes that break down warfarin more slowly than average—those people would need a lower dose of warfarin.

How does genetic testing work for warfarin patients? About one-third of the population carries a variation of a warfarin-metabolizing gene that results in slower warfarin metabolism. Scientists have identified the genes code for these key warfarin-metabolizing enzymes and are developing accurate and relatively inexpensive tests for these genes (about $350). If new patients with this gene variation could be identified, physicians could start them on lower warfarin doses to start and minimize the risk of serious bleeding internally. This may be more than you want to know, but hang on …..you and your clinician may find it interesting. _______________________________ Warfarin produces its chemical effect by interfering with the synthesis (combining of two or more entities to form something new) of vitamin K–dependent clotting factors through preventing VKORC1 (Vitamin K epOxide Reductase Complex subunit 1; an enzyme) from acting normally. This interferes with carboxylation (modification) of glutamic acid (an amino acid used by the body to build proteins ) residing on

coagulation factors II, VII, IX, and X (each factor has a different function during clotting) as well as the anticoagulant proteins C, S, and Z by glutamyl carboxylase (an enzyme which oxidizes Vitamin K). Depletion of reduced vitamin K leads to the production of nonfunctional coagulation factors, producing anticoagulation (abnormal clotting). Various research studies have implicated other genes in the variability of warfarin dosing in some patients. These include GGCX (a gene that encodes an enzyme which modifies the vitamin K-dependent protein). Other genes that are involved in transporting vitamin K warfarin including apolipoprotein E and P-glycoprotein, and additional genes involved in vitamin Kâ&#x20AC;&#x201C;epoxide metabolism. _______________________________ By identifying people who carry genes for the slower metabolizing enzymes, we could reduce serious bleeding events from 27.6% to 12.6%. Warfarin-related strokes could be cut by half. Physicians may under-dose or hesitate to prescribe warfarin because of a bleeding risk. In this case, genotyping can help doctors to identify persons with normal warfarin metabolism and start them on warfarin without under-dosing and reduce stroke events. This year an estimated 85,000 patients will suffer serious bleeds and almost 17,000 strokes. Could genetic testing avoid these? It may be possible.

How do these complications affect my health care? Bleeding events and strokes are expensive to treat. On average, the direct healthcare costs of treating a bleeding event is $13,500, and the cost of treating a stroke is $39,000. By reducing the number of these serious events, the cost of healthcare should only go down. Although this enzyme test is not currently covered by insurance, the $350 cost of this gene test is pale compared to a hospital stay and bill for $13,000 plus dollars. A rapid test to determine warfarin assimilation and correct dosing could give us results in minutes or a few hours rather than days or weeks of guessing and risk. Unlike DNA testing possibilities, weekly testing of INR is covered by insurance and available to patients today. As discussed, the high cost of medical complications associated with warfarin therapy can be greatly reduced while improving quality of life, state of mind and emotional confidence. In the very near future, DNA testing to more accurately determine warfarin dosing for patients will become available, but until then, manage what can be managed with current technology for warfarin therapy. __________________________________ INR References: PGXL Laboratories; Genelex Corporation; DNA Direct; Kimball Genetics.

Heart Valves: Open

and shut

The Patients Guide to Heart Valve Surgery Medtronic, Inc.

Your heart has four valves made up of tissue flaps called leaflets that open and close, allowing blood to move between your heart’s four chambers. When valves are operating normally, they work with the heart to permit continuous blood flow during rest and exercise. Two valves are located on the right side of the heart where oxygen-poor blood returns from the body: They are the tricuspid valve and the pulmonary valve. The other two valves are located on the left side of the heart, where oxygen-rich blood returns from the lungs to be pumped out to the body. These are the mitral valve and the aortic valve. About five million Americans are diagnosed with heart valve disease each year. Heart valve disease can affect any one or more of the heart’s four valves. When valves are damaged, this can disrupt normal blood flow through the heart. Heart valves can develop one or both of the following conditions: - Stenosis; The valve opening becomes narrow. - Regurgitation or Insufficiency; The valve may not close completely. Over time, calcium deposits can collect around your normal valve, causing a narrowing of the valve opening causing valve

stenosis. When the valve narrows, the heart doesn’t pump as well which can cause several problems. For instance, if the mitral valve is narrow. less blood is able to fill the ventricle when the left atrium contracts. This limits the amount of blood pumped out to the body. Sometimes the valve leaflets become damaged and fail to close completely causing valve insufficiency. When this happens, some of the blood can leak backwards instead of going forwards. This valve condition impairs the heart’s ability to pump the necessary amount of blood to the rest of the body. If the mitral valve does not close completely, blood can pass back into the left atrium instead of moving forward through the aorta. Blood regurgitating or being forced back into the atrium can build pressure in the atrium and the lungs. This excess pressure in the lungs keeps them from working properly. Doctors can detect a heart valve problem by your symptoms, listening to your heart and testing. Operations to replace poorly functioning heart valves are common procedures. They are done to improve the health and vigor of people with heart valve diseases. The type of valve disease and the general health of the patient are determining factors in choosing

which kind of heart valve to use as a replacement. Tissue heart valves are usually made from animal tissues, either animal heart valve tissue or animal pericardial tissue. The tissue is treated to prevent rejection and calcification. There are alternatives to animal tissue valves. In some cases a homograft or human aortic valve can be implanted. Homograft valves are donated by patients and harvested after the patient dies. The durability of homograft valves is comparable to porcine and bovine tissue valves. Another procedure for aortic valve replacement is the Ross procedure (or pulmonary autograft). In a Ross procedure, the aortic valve is removed and replaced with the patient’s own pulmonary valve. A pulmonary homograft (pulmonary valve taken from a cadaver) is then used to replace the patient’s own pulmonary valve. This procedure was first used in 1967 and is used primarily in children, because the procedure allows the patient’s own pulmonary valve (now in the aortic position) to grow with the child. Mechanical valves are designed to outlast the patient, and have typically been stresstested to last several hundred years. Although mechanical valves are long-lasting and generally only one surgery is needed, there is an increased risk of blood clots forming with mechanical valves. As a result, mechanical valve recipients must generally take anti-coagulant (blood thinning) drugs such as warfarin for the rest of their lives.

More than 80 models of artificial valves have been introduced since 1950. Three main designs of mechanical valves exist: the caged ball valve, the tilting disc (single leaflet) valve, and the bileaflet valve. The only Food and Drug Administration (FDA)–approved caged ball valve is the Starr-Edwards valve.

Tilting disc and bileaflet valves have a loud, high-frequency, metallic closing sound. This frequently can be heard without a stethoscope. Absence of this distinct closing sound is abnormal and implies valve dysfunction. These valves also may have a soft opening sound. Caged ball valves (Starr-Edwards) have low-frequency opening and closing sounds of nearly equal intensity. Mechanical heart valves have been traditionally considered to be more durable in comparison to tissue valves. The struts and occluders are made out of either pyrolytic carbon or titanium coated with pyrolytic carbon, and the sewing ring cuff is Teflon, polyester or dacron. The major load arises from transvalvular pressure generated at and after valve closure, and in cases where structural failure does happen, it is usually as a result of occluder impact on the components.

Impact wear usually occurs in the hinge regions of bileaflets, between the occluder and ring in tilting-discs, and between the ball and cage in caged-ball valves. Friction wear occurs between the occluder and strut in tilting-discs, and between the leaflet pivots and hinge cavities in bileaflets.

Bileaflet valves, which consist of two semicircular leaflets that rotate about struts attached to the valve housing. This design was introduced in 1979 and while they take care of some of the issues that were seen in the other models, bileaflets are vulnerable to back-flow and so they cannot be considered as ideal. Bileaflet valves do however provide much more natural blood flow than caged-ball or tilting-disc implants.

These bileaflet valves have the advantage that they have a greater effective opening area (2.4-3.2 square cm c.f. 1.5-2.1 for the singleleaflet valves). Also, they are the least thrombogenic of the artificial valves.

One of the main advantages of these valves is that they are well tolerated by the body. Only a small amount of blood thinner is needed to be taken by the patient each day in order to prevent clotting of the blood when flowing through the valve.

With current monitoring techniques of warfarin levels in the mechanical heart valve patient, the risks associated with MHV replacement is greatly minimized and offers the patient a very high quality of life.

Mechanical heart valves are today very reliable and allow the patient to live a normal life with valves lasting for at least 20 to 30 years.

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How Much...

...does PT/INR self-testing really cost? Philips Remote Cardiac Services / Wayne Carley

This is the most frequently asked question about self-testing, and probably the question that takes the most time to explain. For many people the cost of self-testing is very small or nothing at all. It Depends What it will cost you depends on two things: 1. Your condition (the reason you are taking warfarin) 2. Your individual health insurance plan, and how they cover self-testing Covered medical conditions These are the conditions for which Medicare and most commercial health plans pay for selftesting: •Long-term atrial fibrillation (Afib) •Mechanical heart valve (MHV) •Deep vein thrombosis (DVT) •Pulmonary embolism •Hypercoagulable state If you have one of the above conditions, and are interested in self-testing, here is how insurance coverage determinations are made. First things first INR self-testing requires a prescription, so the first thing you need to do is discuss your interest in self-testing with your doctor or the person who manages your warfarin therapy. If they agree that self-testing may be good for you, he or she will order it for you by completing a form and sending it to a self-testing service company.

The service provider will contact your health insurance company for you and find out if they will pay for your self testing, and if so, how much of the cost will they cover.

The service company will then call you and let you know what your coverage will be, and if there might be any co-payments or deductibles. At that point, you get to decide if you want to begin self-testing or not. The good thing about this process is that you will be able to make an informed decision based on what your cost, if any, will be. This process puts your health management under your control. Medicare Covers 80% For individuals with Medicare and any of the above medical conditions, Medicare will cover 80% of the cost of your self-testing services. These services include filing your Medicare paperwork, self-testing training, the testing meter, the supplies and ongoing phone support.

...about $8 per test. For those with Medicare and a secondary policy such as AARP and many other plans, the secondary plan will pay the remaining 20%, so the patient pays nothing. For those with no secondary policy, the co-pay typically works out to about $8 per test. Other Health Plans Many of the commercial health plans will also pay for INR self-testing, but the specifics of what your plan will cover can only be determined by contacting them, which is what the service provider will do for you when your doctor or warfarin clinic manager recommends you for self-testing.

If your health plan pays for it, here is what you will receive: The testing meter is free, provided to you on permanent loan for as long as you continue to self-test by the service company. They will train you on how to use it, and will provide a toll-free customer service line for any questions. If anything happens to the meter, they will repair or replace it for you at no charge. The service company will also provide you with test strips and any other supplies you need for as long as you continue to self-test. Testing is accurate, fast and simple. Once you have been trained on how to self-test, it usually takes most people about 10 minutes to take their test and to phone in their results to the service company. The service company then creates a report and sends it to your doctor or clinic manager right away so they can see how you are doing and adjust your dose if needed.

Weekly testing is the recommended frequency for most warfarin patients. Until recently, warfarin patients were told to test once a month at their local lab or clinic. Recent clinical studies however, now show that individuals who test more frequently spend more time in range, greatly reducing risks associated with warfarin use.

...the price of a nice lunch... Cost versus Benefit When a patient and their family considers the risks of dangerous complications and the expensive inconvenience of a hospital stay due to a clot or bleed caused by being out of range, the minimal cost of self-testing seems well worth the lower risks. The added convenience of being able to self-test when you travel, or to test from home when the weather makes getting to the clinic difficult or dangerous is another important benefit. For the price of a nice lunch, warfarin patients and their loved ones can have the control and peace of mind that add great value to the quality of life. Knowing the status of your health brings confidence and eliminates many fears associated with complex medical conditions. Prevention is everything. Control of your health is priceless. _________________________________ INR

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in certain clinical situations, a practitioner may need to intervene with administration of Vitamin K if the INR is very high. There are expert/consensus guidelines that address this important clinical situation. On the other hand, if the INR is very low, and the patient is recognized to be prone to clotting, then practitioners may recommend adding an immediately acting heparin-type medication to lessen the risk of clotting, until a new dose of warfarin takes effect. Some patients with marked variability of INR on a stable dose of warfarin and in the absence of changing clinical issues may benefit from very small doses of oral Vitamin K (100-200 micrograms/day). Several studies have suggested that this strategy may be useful, especially in patients who may have lower baseline levels and intake of Vitamin K in their diet. There are several methods used to adjust dose of warfarin. Some practitioners make dose adjustments based on experience while others use paper-based systems or computer-based systems. Shepro and Ansell developed a slide-chart system that assists health care providers in managing warfarin dose changes and provides easy access to consensus guidelines from ACCP. A set of dosing rules, based on clinical experience, was created. In this system, dose change recommendations are expressed in 10% to 20% increments. While a 10 % dose change appears easy to implement, this can be challenging when patients have, for example, 5 mg table strength.

5 mg/day = 35 mg/week To decrease weekly dose by 10% = 3.5 mg. Taking 3.5 mg out of the weekly dose, especially when patient has 5 mg tablets is challenging. An array of total weekly warfarin doses that are approximately 10% different from each other was therefore created. In addition, the daily dose schemas in this system are convenient for patients to take and allow for the total weekly dose to be spread out evenly. A minimum number of tablet strengths are utilized with this method. 5 mg/day = 35 mg/week To decrease weekly dose by ~10%, the dose array brings the next weekly dose down to 32.5 mg/week, which is easy to spread out across the week as 5 mg/day for 6 days and 2.5 mg/day for 1 day. This slide-chart system was studied by Shepro and was shown to be readily adopted by health care personnel and contributed to high quality anticoagulation dose management. This system was placed in a slide-chart system and is also available on hand held devices. (www.anticoagulation-advisor.com) Frequency of INR testing Experts recommend that initial INR monitoring be performed every few days until a stable dose response has been achieved. Given the multiple shifting clinical factors

experienced by patients who are hospitalized, many hospitals and acute care settings now require frequent or daily INR for patients who are being initiated or maintained on warfarin. When the INR is stable, the frequency of testing can be reduced to intervals as long as every 4 weeks. A gradual decrease in the frequency of INR assessment is recommended. More frequent INR should be performed when new medications or clinical characteristics of patients change. Even in clinically stable patients, more frequent testing may lead to improved outcomes of safety, effectiveness, and time spent at a therapeutic INR. Patient self-testing and patient self-management For many patients who require long term warfarin therapy, patient self-testing is an effective tool for monitoring therapy and managing dose adjustments. Indeed, in 2008, Medicare and other insurers appropriately expanded coverage of home INR monitoring to include: • Patients with mechanical heart valves • Chronic atrial fibrillation • Venous thromboembolism More recently, patient self-management, in conjunction with essential education and supervision is evolving as a standard of care for many patients who require long term warfarin therapy. A group from Spain demonstrated that self-management of oral anticoagulation can achieve extremely high quality anticoagulation outcomes. A slide-

chart has been designed and published by Shepro and Ansell for these self-management patients and is undergoing study.

Selected References: Ansell J.. Hirsh J., Hylek E, Jacobson A, Crowther M., Palareti G;. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).; American College of Chest Physicians. Chest. 2008 Jun;133(6 Suppl):160S-198S Crowther MA, Ginsberg JB, Kearon C, Harrison L, Johnson J., Massicotte MP, Hirsh J.. A randomized trial comparing 5-mg and 10-mg warfarin loading doses. Arch Intern Med. 1999 Jan 11;159(1):46-8. Ford SK, Moll S. Vitamin K supplementation to decrease variability of International Normalized Ratio in patients on vitamin K antagonists: a literature review. Curr Opin Hematol. 2008 Sep;15(5):504-8. Garcia DA, Hylek E. Warfarin pharmacogenetics. Comment on: N Engl J. Med. 2009 Jun 4;360(23):2474; author reply 2475. N Engl J. Med. 2009 Feb 19;360(8):753-64. Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. Estimation of the warfarin dose with clinical and pharmacogenetic data. International Warfarin Pharmacogenetics Consortium,N Engl J. Med. 2009 Feb 19;360(8):753-64. Menéndez-Jándula B, Souto JC, Oliver A, Montserrat I, Quintana M., Gich I, Bonfill X, Fontcuberta J.. Comparing self-management of oral anticoagulant therapy with clinic management: a randomized trial. Ann Intern Med. 2005 Jan 4;142(1):1-10. Shepro DS, Morden N, Shoemaker T. Implementation of a Warfarin Dosing Method at a Community Health Center. Blood 2002;100(11)

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Essential reading for anyone taking Coumadin® or warfarin, with the information your patients need to successfully manage their medications and minimize adverse events.

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PT/INR Self-testing

Here’s why doctors now recommend self-testing for appropriate patients Published studies show that for some chronic warfarin patients, self-testing may be a better option than traditional lab or office testing. Self-testing Can Increase Time in Range 60% 50%

20% 10%

Usual Care 32%

30%

Patient Self-Testing 56%

40%

Weekly Self-testing Can Improve Patient Outcomes

-30 -40 -50

Death -39%

-20

Thromboembolic Events -55%

-10

Major Hemorrhagic -35%

Increase Time in Therapeutic Range A randomized study (Byeth RJ et al. Annals of Internal Medicine 2000;133:687-695) of 365 patients on warfarin therapy demonstrated that those who self-tested were in range 56% of the time while patients who received usual care were in range only 32% of the time. Lower Risk An analysis of 14 studies on PT/INR self-testing (Henagen C. et al. Lancet 2006;367:404-11) revealed that “patients capable of self-monitoring their warfarin therapy could benefit from a one-third reduction in death from all causes.”

Medicare has approved INR self-testing for selected patients on long-term warfarin therapy In a 2001 decision, medicare concluded “that home PT/INR monitoring significantly improved time in therapeutic range for selected groups of patients, compared to testing done in physician offices or anticoagulation clinics. “ Increased Time in Therapeutic Range results in fewer Warfarin – related complications. (CMS Decision Memorandum #CAG-00087N September 18, 2001.)

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To learn more about our INR self-testing service, call 1-877-799-3126, or visit www.inrselftest.com Service available only by prescription.

Philips Remote Cardiac Services 7 Waterside Crossing Windsor, CT 06095 Telephone: 877.729.8350