Preventing First-Ever Stroke

Farzaneh Sorond, MD, PhD
Associate Neurologist, Brigham and Women's Hospital, Boston, Massachusetts
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As the second leading cause of death, stroke is a significant healthcare problem in the world [1].  Worldwide, about 15 million people suffer from stroke every year with 5 million dying and another 5 million living with permanent disability [2, 3]. By 2015 there will be approximately18 million first-ever strokes and 6.5 million deaths from stroke for all ages [1]. In the United States, stroke is the third leading cause of death. There are more than 700,000 strokes in the United States each year, resulting in more than 160,000 deaths annually, with 4.8 million stroke survivors alive today [4]. On the average, someone in the United States suffers a stroke every 45 seconds and every 3 to 4 minutes someone dies of a stroke [5, 6]. Stroke is also a leading cause of disability, with 20% of survivors requiring institutional care after 3 months and 15% to 30% being permanently disabled [4].

While these numbers may seem astonishingly large, they are estimates of strokes based on the clinical event only and do not account for silent strokes. As such they significantly underestimate the true prevalence of this disease. Silent cerebral infarctions, which were first described by Fisher [7], have been associated with an increased risk of incident stroke and cognitive impairment [8]. With the recent advent of neuroimaging, we now know that up to one-third of patients with transient ischemic attacks (TIA) and no physical examination changes have infarcts on scans [9]. More recent imaging studies have reported the prevalence of 5.84% to 28% for these lesions by MRI [10-12]. Recent data from the Framingham Offspring Study shows a prevalence of 10.7% among more than 2000 mid-life (mean age, 61 years), community-dwelling people who were clinically stroke-free [10]. Risk factors associated with clinical stroke such as age, sex, diabetes mellitus, atrial fibrillation, hypertension, carotid artery disease and cigarette smoking have also been associated with these silent strokes [9, 12-17]. The association of these clinical stroke risk factors with silent stroke reinforces the importance of early detection and treatment of risk factors in mid-life.

Indeed, the greatest impact on stroke as a public health issue is via preventive measures. Stroke prevention is two tiered, primary and secondary. Primary prevention targets recognized risk factors with the aim of reducing the incidence of first-ever-stroke. Secondary prevention aims to reduce recurrent stroke in those who have suffered a TIA or stroke. While secondary prevention and acute management of stroke have been studied using the standardized clinical trials and the findings emphasized in clinical practice guidelines (for detailed review see [18, 19]), given that almost 70% of strokes are first-ever-strokes, until recently, primary stroke prevention has not received proportional public health attention. In 2004, the “Stroke Risk Assessment and Future Stroke Primary Prevention Trials” workshop was sponsored by the NINDS to discuss and identify the challenges that have delayed primary stroke prevention trials [20]. The report of this workshop was published in 2005 [21] and in 2006 the AHA/ASA issued its first guidelines on primary stroke prevention [4]. Some specific challenges identified in this workshop included the [20]:

• definition of an at-risk population
• choice of treatment and likelihood of adoption
• inclusion of the elderly who may be at the highest risk, but face the issues of attrition and compliance
• choice of surrogate markers
• issue of subclinical disease and silent strokes

Despite these challenges, the ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events; http://clinicaltrials.gov) trial was started in 2007. ARRIVE is a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of daily 100mg enteric-coated Aspirin in preventing a first stroke or heart attack in patients at moderate risk. Moderate risk is defined as approximately 30% 10-year cardiovascular disease event risk; or 10-20%, 10-year coronary heart disease event risk. Approximately 12,000 patients will be enrolled in five countries (Germany, Italy, Spain, the United Kingdom, and the United States) with 400 study sites participating. It is estimated that the trial will take approximately 5 years to reach the primary endpoint of an adequate number of events associated with cardiovascular disease for analysis.

Until the results of the ARRIVE trial are available and more future novel primary prevention trials have been launched, we have some important measures that we can implement. Extensive evidence is available identifying a variety of specific factors that increase the risk of a first-ever-stroke; hence providing us with strategies for reducing that risk. The risk factors for all stroke subtypes can be divided into, non-modifiable, modifiable or potentially modifiable. The non-modifiable risk factors are age, gender, race and family history. The modifiable risk factors are hypertension, heart disease, atrial fibrillation, diabetes, hypercholesterolemia, carotid stenosis and prior strokes or TIAs. Risk factors that are modified by behavioral changes include smoking, alcohol, diet and exercise for reducing obesity & waist-hip ratio and stress reduction. Here is a brief summary of what the AHA/ASA recommended in 2006 [4]:

• Each patient should have their stroke risk assessed. This can be achieved through risk-assessment tools such as the Framingham Stroke Profile.
• Each patient should have regular screening for hypertension (at least every 2 years in adults and more frequently in minority populations and the elderly). Diet and lifestyle changes should be implemented and medications started.
• In patients with diabetes, hypertension should be tightly controlled, possibly with an ACE inhibitor or an ARB. Also, a statin should be considered to lower the risk of a first stroke is recommended.
• Patients with atrial fibrillation who have valvular heart disease (particularly those with mechanical heart valves) should be anticoagulated. Specific strategies are also recommended to manage a number or other cardiac conditions such as MI, heart failure and others.
• Individuals with elevated total cholesterol, or with elevated non–HDL cholesterol in the presence of hypertriglyceridemia should be treated.
• Patients with asymptomatic carotid artery stenosis should be screened for other treatable causes of stroke. All identified stroke risk factors should be treated. Aspirin and carotid revascularization should be considered in appropriate patients.
• Children with sickle cell disease should be screened with transcranial Doppler ultrasound starting at 2 years of age and transfusion therapy should be considered for those at elevated stroke risk.
• Postmenopausal hormone therapy should not be used for primary prevention of stroke.
• Diet and nutrition are major components of risk reduction. Reduced sodium and increased potassium intake is recommended to lower blood pressure in persons with hypertension. A diet, which is rich in fruit and vegetables, and low-fat dairy products and is reduced in saturated and total fat (such as the DASH diet) should be considered.
• Physical activity should be increased. The CDC and the National Institutes of Health recommend at least 30 minutes of moderate intensity activity daily.
• Weight reduction is recommended because it lowers blood pressure.
• Heavy drinkers should reduce their alcohol consumption. For those who consume alcohol, no more than 2 drinks per day for men and 1 drink per day for nonpregnant women, is recommended.
• Drug abuse should be identified and managed through counseling.
• Oral contraceptives should be discouraged in women with additional risk factors such as cigarette smoking or prior thromboembolic events
• Sleep-Disordered Breathing should be identified and treated especially in the setting of drug-resistant hypertension.

There are also a number of risk factors that may be potentially modifiable, but we just don’t have conclusive data on them. These include hyperhomocysteinemia, elevated lipoprotein a (LP(a)) levels, prothrombotic states, inflammation, patent foramen ovale, and migraine.

Given that the highest stroke burden is in the low and middle income regions for the world, the largest impact will come from primary prevention [1]. Over 60% of stroke mortality is attributable to a few modifiable risks such tobacco use, raised blood pressure, and poor diet [1]. The impact of a combination of healthy life style factors on primary stroke prevention was recently studied in more than 114,000 primarily white participants of the Nurses Health Study and Health Professionals Follow-up Study.  The results showed that a low-risk life style (not smoking, diet, exercise, optimal body weight and low alcohol consumption) was associated with a substantial reduction (about 70-80%) of stroke, especially ischemic stroke [22]. Therefore, more aggressive primary stroke prevention will have a significant impact on lowering the personal, social and economic burden of this disabling disease. The challenge is to veer off the many temptations of the unhealthy life style choices and promote sustainable low-risk life style changes across all communities, especially the low and middle-income regions of the world who are most at risk. 

Better Oral Anticoagulation; New agent or better management method? [Part I]

Henry I. Bussey, PharmD
Professor, College of Pharmacy, The University of Texas at Austin; President and Senior Editor, ClotCare Inc., ClotCare.com; and President, Genesis Clinical Research, San Antonio, Texas

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Disclosures:  Dr. Bussey serves as a consultant to Genesis Advanced Technologies, Inc. of Lakehills, Texas in the development of The ClotFree System and, in partnership with Marie B. Walker, holds a provisional patent on 3 new vitamin K antagonist products.  His current research in this area is funded by Roche Diagnostics, Inc. of Indianapolis, Indiana and the Chest Foundation of the American College of Chest Physicians

Background and Introduction

Some time ago a senior member of the pharmaceutical industry told me: “Henry, we want to compare [the company’s new oral anticoagulant] to well-managed warfarin; we are not interested in comparing it to optimally managed warfarin.”  That view caused me to consider in more detail the relative merits of the new oral anticoagulants currently in development and what should be possible if vitamin K antagonist (VKA) therapy could be easily optimized.  Reviewing the characteristics and clinical data for each of the new agents in development is beyond the scope of this review.  Rather, the new agents will be considered as a group as “non-inferior” to conventional VKA therapy and compared to what the available data suggest might reasonably be accomplished with better VKA management.

If one considers what is know currently about VKA therapy and the new direct thrombin inhibitors (DTI) and anti-factor Xa inhibitors (anti-Xa), it appears that VKA therapy offers several advantages while therapy with the new agents presents several potential pitfalls (Table 1).   Clearly, with VKA therapy the major problem is the difficulty of monitoring and managing such therapy.  If we set aside the management problem for the moment and consider other aspects of VKA therapy (as will be presented in more detail later), it is clear that VKA therapy could be very effective and very safe if only it were managed optimally.  By contrast, the new agents are, for the most part, simply trying to show that they are “non-inferior” to VKA therapy as it currently is managed.

Selected potential problems with the new agents

Potential,  not-yet-recognized adverse effects:  Although the increase in liver toxicity and myocardial infarction seen with ximelagatran have not been seen with the new agents, we must be aware of the potential for these and other adverse effects.

No antidote:  At present, none of the new oral anticoagulants can be readily reversed.  This may be of limited significance if toxicity and/or bleeding is limited and/or if the agent has a short duration of action.  But it is my understanding that one lawsuit has already been filed claiming that the consent form signed by a study patient did not adequately inform the patient that there was no specific way to reverse the effect of the new anticoagulant if bleeding should occur.  Also, at least one attorney’s website already has questioned the safety of one new agent and posted an invitation for harmed patients to contact his office (see http://seelielaw.com/blog/?p=74).

No test for dosage adjustment, assessing adherence, or evaluating interactions:  Although the lack of need to monitor the INR often is heralded as an advantage of the new agents, the lack of such monitoring also presents several problems.  There is no way to assess whether a dosage adjustment may be warranted, there is no way to confirm that the patient is actually taking an adequate dose (or is adhering to the regimen), and there is no way to monitor the patient (other than the development of bleeding or clotting events) for potentially interacting drugs or other factors.  Although the number of factors that may interact with the new agents may be limited, the absence of a monitoring test will make it difficult (if not impossible) to identify such interactions in routine clinical practice.  Prospective pharmacokinetic drug interaction studies can confirm that a given interaction does not occur predictably in all patients but, unfortunately, such studies can not exclude the possibility that certain patients or sub-groups of patients will exhibit a dangerous interaction.  For example, our group conducted a randomized, double-blind, placebo-controlled trial to evaluate the effect of ciprofloxacin on the INR in warfarin-treated patients.  That small trial failed to show any interaction at all between the two medications.1  Even so, clinical experience and other data suggest that such an interaction does occur in some patients.  Whether the interaction is related to the patient having an infection, being febrile, having a particular genetic polymorphism, or some other factor is not certain; but even the investigators of our negative study are convinced that such an interaction does occur from time to time.

Pharmacokinetic considerations: Several of the new agents have a relatively short half-life, exhibit limited oral bioavailability, and rely on hepatic and/or renal elimination.  The short half-life may jeopardize the safety and efficacy of the agent in clinical practice because of limited or sporadic patient adherence to the regimen.  In general, agents that are not well absorbed following oral administration carry the potential for other factors to substantially increase or decrease the extent of absorption which could result in excessive or inadequate anticoagulation, respectively.  Those agents that depend on renal and/or hepatic elimination, of course, are subject to requiring dosage adjustments in the face of renal or hepatic disease, or when other medications are administered that may alter the renal or hepatic clearance of the anticoagulant.  Unfortunately, there is no “INR –equivalent” method to assess either the need for - or the appropriateness of  - dosage changes in such situations.

Learning to Take Responsibility for my Health Care

Mark Lindsay
NATF Patient Advocacy Committee

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Abstract:  The writer, as a surgical patient, discovers that he has developed a massive DVT.  His concerns lead him to self education about his condition and to seeking out multiple sources of information and care.  He adopts three guidelines: 1. learn the risks, 2. get a second opinion, and 3. take responsibility for your own health care.

The pain in my left knee had been increasing over the 25 years since I damaged it in my early 30’s.  The orthopedic surgeon referred to me by my primary care physician, ordered an MRI and informed me that arthroscopic surgery was the correct treatment.  He offered me an outpatient surgery appointment for two days later.  It seemed like a routine procedure, and I accepted it without further consideration.

When my leg became red, hot and swollen a few days after the operation, the surgeon responded to my phone call by confirming that I didn’t have a fever and that I had a follow up appointment in a few days and I should come and see him then.  I followed his advice.  When he saw me one week after the surgery, the pain in my leg was extreme.  He requested an ultrasound and I learned that all the deep veins in my left leg were completely clotted well up into my abdomen.  He told me to get myself to my local hospital.  I asked who would be overseeing my care and he said that since this didn’t relate to my surgery, that my primary care physician would be in charge.  Since my PCP was away, the doctor covering for him prescribed low molecular weight heparin injections and warfarin.

24 hours after I was admitted, I had my first visit from a physician, who was covering for the person who was covering for my doctor.  I asked him what my treatment plan was, and he said that I could go home, that I would be taking warfarin for 6 months, and that I would have my INR checked regularly.  When I asked what INR stood for he said he didn’t know but that it measured the coagulability of my blood. 

When I returned home, the swelling in my leg continued to increase.  Standing up caused dizzying pains in my leg, chest and head, and I spent most of my time in bed.  My primary care physician said that I would be uncomfortable for several weeks but that in 6 months I would be back to normal.

Two weeks after the surgery, I began to question whether I was getting the best information and treatment and began to research deep vein thrombosis on the internet.  I discovered that there was a wealth of information available. 

I learned that many doctors prescribe compression stockings for DVT although no one had suggested these to me.  After calling a medical supply store to see if I could purchase them, I was told that I needed a prescription.  I called my PCP who said he didn’t know if stockings would help.  He referred me to a vascular surgeon who said that I wouldn’t like compression stockings since they would be uncomfortable, but that I should elevate my heel higher than my heart to decrease the swelling.  His recommendation was to lie on the floor with my foot on the edge of a sofa.  Within two days of elevating my foot, the swelling and pain decreased dramatically.

I also learned from the internet that a proclivity for developing blood clots can be inherited.  I remembered that 45 years earlier, my father had developed blood clots following an appendectomy.  I then recalled that my father’s brother had developed clots in his legs and lungs following a hip replacement.

At this point, I had a revelation.  If I wanted the best outcomes from my health care, I needed to get involved.  I created three basic guidelines for myself.

1. Always ask what the risks are.  If I had done this before the surgery I might have learned about the relatively high incidence of clots following knee and hip surgery.
2. Always get a second opinion.  Every doctor has different experiences from which to draw and there are many possible treatments and an even larger quantity of unknowns.
3. Always remember that you are primarily responsible for your own health care.  You make the ultimate choices as to whether or not to undergo a procedure or follow a certain treatment.  You need to be well informed about the alternatives and the possibilities.

I asked a friend who works as a nurse at one of the major teaching hospitals in Boston to recommend a vascular surgeon who could make the time to listen to my questions and answer them, and who would be knowledgeable about the best treatment options. 

This surgeon made sure I got the best answers he had to offer and that I understood them.  He immediately prescribed compression stockings which substantially decreased the pain in my leg.  When he suggested clot dissolving thrombolytic drugs, I knew enough to ask, “What are the risks?”  When he said there could be 1% chance of death from intra-cranial bleeding, I knew I wanted a second opinion.  My uncle recommended Dr. Goldhaber at the Brigham who had treated his DVT and PE.

Dr. Goldhaber said I could make my own choice, but that he felt that eight weeks after the initial clotting episode, thrombolysis had a low probability of success, and that there was a small but real risk of fatal bleeding.  He recommended that I use the Brigham’s anti-coagulation service to monitor my INR and to answer any questions I had about drug and food interactions with warfarin.  He also advised me to join the Brigham Support Group to draw on other patients learning to answer my questions about self-care and dealing with the uncertainties of my new situation.

I finally felt that I could say with confidence that I had the best medical advice available, and that I could make informed choices and follow the recommended treatment plans knowledgeably and effectively.  While DVT and PE patients face many unknowns, well-informed patients give themselves the best chance of avoiding mistakes and living long and healthy lives.  Today I am working to pass that information on to other patients and their caregivers in hopes that it may be of some use in improving their futures as well.

 

An Interdisciplinary Approach to VTE Prevention in a Large Academic Hospital

Maichi T. Tran, PharmD, BCPS, Naomi F. Botkin, MD, Jennifer L. Donovan, PharmD, Paul B. Shaw, PharmD, Joel M. Gore, MD

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A interdisciplinary approach to venous thromboembolism (VTE) prevention is instrumental in achieving optimal patient outcomes. It is prudent to develop a hospital-wide policy and clinical practice guidelines to help providers in the identification of risk factors and choice of prophylactic measures, if appropriate. (1) Hospital administration and leadership must make VTE prevention an institution-wide initiative and dedicate resources to develop and implement a strategic plan to minimize the risk of VTE while patients are hospitalized. National quality organizations have identified VTE prevention measures as current and future quality indicators for US hospitals. (Table 1) A descriptive report of how a VTE prevention program is being developed and implemented in a large academic hospital will be presented.

Epidemiologic data describing the burden of VTE on patient outcomes and evidence-based guidelines that address prevention of VTE are well-known. (1-6) Despite strong data supporting VTE prophylaxis, multiple medical record audits have demonstrated under use of prophylaxis in hospitalized patients. (3, 7, 8) Quality performance measures can help improve accountability and change clinical practice. However, the approach to improving risk assessment and utilization may vary depending on your practice setting and hospital infrastructure.

UMass Memorial Medical Center (UMMMC) is a large, 840 patient bed, tertiary care, academic medical center located in Central New England, capable of caring for 120 critically ill patients in our intensive care units on a daily basis. Although VTE potentially affects all hospitalized patients, we initially decided to direct our focus toward this high risk population. The Critical Care Operations Committee, (CCOC) led by Drs. Richard Irwin and Craig Lilly coordinates strategies to standardize and optimize the care of critically ill patients at UMMMC through the interdisciplinary efforts of expert physicians, nurses, nurse practitioners, physician assistants, and pharmacists. This team of experts is responsible for implementing best practices and tracking outcomes in critically-ill patients. The CCOC established VTE prevention as a priority initiative.

In 2006, the CCOC appointed a physician champion, Dr. Naomi Botkin, to lead the development of a clinical practice guideline (CPG) for the prevention of VTE in adult intensive care (ICU) patients. The physician champion teamed up with a pharmacist champion and recruited members of the ICU staff to participate in the development of this CPG. The aim of the CPG was to improve adherence to accepted VTE prophylaxis guidelines in the critical care setting, and thereby decrease the incidence of in-hospital VTE. This CPG outlines recommendations for the preferred prophylactic measures (pharmacologic and non-pharmacologic) for all ICU patients including those who have extremes of body weight, renal insufficiency, allergic to heparin products, or have risk factors for bleeding. The CPG was made available online for all hospital staff to access and all were educated through inservices. Venous thromboembolism prophylaxis was made a line item on the Care Plan page of our electronic medical record charting program, VISICU(TM). The Care Plan page is viewed by members of the eICU(TM) staff (a remote team of UMMMC intensivists, nurse practitioners, nurses, and pharmacists) in addition to the core ICU team on a daily basis to ensure that all standards of ICU care are met. The eICU(TM) team updates the Care Plan daily with documentation on VTE prohylaxis using a drop down menu of the following choices: (1) Drug therapy, (2) Compression devices, (3) Combined compression device and drug therapy, (4) Full anticoagulation already in affect, (5) Not indicated-patient coagulopathic, or (6) Not indicated-patient ambulating. If no actions are implemented, a member of the eICU(TM) team will notify a member of the core ICU team to address the issue.

A retrospective baseline assessment based on a chart review of eligible adult ICU patients prior to the CPG rollout showed that VTE prophylaxis rates needed improvement. A snapshot evaluation of all eligible adult ICU patients across the entire Medical Center was completed by pharmacists demonstrating a significant increase in utilization of any prophylactic measure at 1 and 7 months, respectively post implementation of the CPG. Our VTE prophylaxis performance is now tracked by the eICU(TM) Program Performance and Benchmarking Report. According to this report, we currenty have had the highest compliance to VTE prophylaxis for over 3 consecutive quarters. The VISICU(TM) network includes over 300 hospitals across the nation.

Recognizing that VTE is not just a concern exclusive to the critically ill population, we quickly proceeded to direct our efforts toward non-critically ill surgical and medical patients. Rolling out a strategic plan in the non-ICU areas presented different challenges as we do not have an electronic medical record system available outside of the ICU. To reduce the chance of error of omission, as there is no electronic or human alert system in non-ICU areas; check box options for VTE prophylaxis were added to the comprehensive pre-printed post-operative orders forms. All key surgeon leaders, including our physician quality officer, Dr. Margaret Hudlin, for the surgical areas, approved these order forms and required use of these order forms in all patients undergoing major surgery. Education was also provided to all involved hospital staff. As a result of this collaborative approach, our organization has achieved above target results for VTE prophylaxis for the Surgical Care Improvement Project (SCIP).

Once we addressed the ICU and surgical needs, we progressed to the acute care areas. In 2007, the Anticoagulation Task Force was assembled primarily to help prepare the organization?s compliance with the National Patient Safety Goal for Anticoagulation. This interdisciplinary Task Force which is led by Drs. Maichi Tran and Joel Gore is responsible for identifying areas of improvement in anticoagulation management across the entire organization. A work plan was developed outlining all Joint Commission implementation standards, timeline(s), stakeholders, and status of progress. A hospital-wide VTE prevention program was established as a priority item on this work plan. The VTE prevention CPG originally intended for adult ICU patients was expanded to include acute care patients. A dedicated pre-printed order form was developed and includes general principles to optimize VTE prevention, common risk factors for VTE, pharmacologic and non-pharmacologic recommendations from the 2008 ACCP Chest guidelines for VTE prevention (1), and options for why prophylaxis may not be indicated. A hospital-wide policy on VTE prevention and data tracking program is also underway. The purpose of the VTE prevention policy is to hold all providers accountable for VTE risk factor assessment and enforce the need for implementation and documentation of an action plan to address the patient?s needs. Ongoing performance tracking and real time reporting will help to identify any areas of improvement so that appropriate interventions may be instituted (e.g. targeted education, revision of order forms). An education plan is also being developed to target health care providers and patients and their family members/caregivers.

Some institutions have implemented an electronic alert where the physician is notified if the patient is not on a prophylactic measure but is considered to be at risk. (9, 10) Our institution has taken a interdisciplinary approach to VTE prevention integrated with a hybrid of provider education, preprinted order forms, clinical practice guidelines, and human alerts. It is important for health care providers to evaluate the infrastructure and resources of their institution to establish which strategy works best to optimize VTE prevention and reduce the incidence of in-hospital DVT and PE. Some key steps that may help health care providers organize a systematic approach to developing and implementing a program in your institution are outlined in Table 2.

Table 1: Quality Measures for VTE Prevention
National Quality Forum (NQF) and Joint Commission

Surgical Care Improvement Project (First 2 VTE measures endorsed by NQF)*

1. VTE prophylaxis ordered in surgical patients
2. VTE prophylaxis administered in surgical patients (based on ACCP Consensus recommendations) within 24 hours before or after surgery

New VTE Prophylaxis Measures recommended by NQF**

1. VTE prophylaxis of all hospitalized patients within 24 hours of admission or surgery, or a documented risk assessment showing that the patient does not need prophylaxis
2. VTE prophylaxis/documentation of all hospitalized patients within 24 hours after ICU admission or surgery
3. Incidence of potentially preventable VTE-proportion of patients with hospital-acquired VTE who had not received VTE prophylaxis prior to the event

National Patient Safety Goals (NPSG) for Anticoagulation (go to www.jointcommission.org/npsg for full list of goals)**

1. The organization implements a defined anticoagulation management program to individualize the care provided to each patient receiving anticoagulant therapy.
2. The organization uses approved protocols for the initiation and maintenance of anticoagulation therapy appropriate to the medication used, to the condition being treated, and the potential for drug interactions.
3. The organization has a written policy that addresses baseline and ongoing laboratory tests that are required for heparin and low molecular weight heparin therapies.
4. The organization evaluates its anticoagulation safety practices, takes appropriate action to improve its practices, and measures the effectiveness of those actions on a regular basis.

*Current VTE prevention measures
**Future anticoagulation and VTE prevention measures (NQF recommended measures expected September 2009, NPSG for Anticoagulation due January 1, 2009)

Table 2: Key steps to successfully developing and implementing a VTE prevention program in your institution:

1. Gain senior hospital administration buy in and support

2. Develop Task Force and Work Plan
a. Assemble interdisciplinary group led by champion(s)
b. Recruit in-hospital/local content experts (Cardiologists, Hematologists, Surgeons, Pharmacists, Nurse Practitioners, Nurses, Quality Officers)
c. Build consensus with clinical leaders in organization
d. Meet regularly, document minutes
e. Develop a work plan with tasks, accountable parties, status, timeline

3. Know the current quality measures and those in the pipeline a. Surgical Care Improvement Project-VTE b. National Patient Safety Goals for Anticoagulation c. New VTE measures

4. Clinical Practice Guideline Development
a. Refer to published national guidelines on VTE prevention
b. Review CPGs from other hospitals
c. Include risk assessment/stratification
d. Include methods of prophylaxis
e. Include possible reasons for not giving any prophylaxis
f. Expect that select high risk patients may need special attention (e.g. pediatric, orthopedic, obstetrics)*

5. Policy Development
a. Urge the need for identifying patients at risk
b. Urge the need to implement prophylactic measures in patients at risk
c. Establish accountability

6. Education
a. Patient/Family Education
b. Health Care Provider Education

7. Develop System for ongoing Quality Improvement
a. Contact your Information Support (IS) department
b. Gather baseline data
c. Real time reporting, if possible
d. Make mid-course adjustments if necessary

*At the present time, the UMMMC VTE Prevention Program only applies to adult patients.

Changes to the 8th American College of Chest Physicians Evidence - Based Clinical Practice Guidelines

Mark Crowther, MD, Msc, FRCPC
Professor and Chair, Division of Hematology and Thromboembolism, St. Joseph's Healthcare and McMaster University, Hamilton, Ontario, CANADA

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The 8th American College of Chest Physicians (ACCP) Guideline contains a number of changes from the 7th edition. This brief review focuses on several of these revisions that are of particular methodological or clinical importance. Changes discussed include modifications to the GRADE system (1), and recommendations for the use of parenteral anticoagulants (2)and oral anticoagulants (3). General changes in the 8th Guidelines including increased numbers of non-North American experts (to increase generalizability of the recommendations), increased use of tables and evidence summaries (allowing readers to reassure themselves of the evidence upon which recommendations are based) and more rigorous adherence to the GRADE recommendation process.

Grading recommendations (1): A strength of the ACCP Guideline development process is explicit summary of the evidence supporting particular recommendations, coupled with the use of a rigorously defined grading system. This system allows readers to understand both the strength of recommendation (1 – a strong recommendation or 2 - a weak recommendation), as well as that of the evidence supporting the recommendation (A –consistent evidence from randomized controlled trials [RCTs] without important limitations or exceptionally strong evidence from observational studies, B - evidence from RCTs with important limitations [inconsistent results, methodologic flaws, indirect or imprecise results], or very strong evidence from observational studies, or C - evidence for at least one critical outcome from observational studies, case series, or from RCTs with serious flaws or indirect evidence). This system results in simple but robust recommendations that can be used to guide the care of patients. A 1A grade is a strong recommendation, based on high quality evidence, in which the desirable effects of the intervention in question clearly outweigh undesirable effects. An 1A recommendation applies to most patients in most clinical circumstances and clinicians faced with a patient who has a condition with an 1A recommendation should strongly consider implementing this recommendation or, if choosing to not implement the recommendation, should clearly document their rationale for not doing so. A 2C recommendation, in contrast, is a weak recommendation, being based on low or very low-quality evidence, with a close balance between desirable effects and undesirable effects. When faced with a clinical condition with a 2C recommendation, clinicians should carefully inform patients of the various options available and, taking into account patient and system values and preferences, should assist the patient in making a choice of therapies based on their needs. A common misconception is that a 2C recommendation is a recommendation “against” a therapy; it is not, rather it indicates that a carefully performed summary of available evidence does not strongly support any one treatment option. A “C” recommendation could be upgraded with the provision of additional evidence and, thus, this level of recommendation should suggest topics within which additional research projects might be considered.
Changes between the 7th and 8th edition include the elimination of the 1C+ and 2C+ grades. These grades were reserved for recommendations in which the evidence was felt to be strong, but not derived from RCTs. In the 2008 Grade recommendation exceptionally strong evidence derived from sources other than RCTs might result in an “A” recommendation; in other cases it would result in a “B”, or “C” recommendation. An evolving concept in the development of the GRADE system has been the incorporation of patient values and preferences into the interpretation of the grade, as well as the recognition that societal values may also influence the strength of a recommendation. For example, a therapy which is expensive and of unknown clinical benefit might receive a strong recommendation against its use even if there are no RCTs proving its lack of worth. In the chapter on heparin-induced thrombocytopenia (HIT) the authors make a strong recommendation against the use of routine HIT antibody testing in patients without clinical evidence of the condition since the costs and unwanted outcomes of measurement are overwhelmingly likely to outweigh the benefits.
The success of the GRADE classification is proved by its adoption outside the Antithrombotic guidelines; numerous professional societies, government agencies and commercial organizations have adopted this scheme to evaluate evidence in their areas of content expertise.

Parenteral anticoagulants (2): A number of recommendations included in the text, but not explicitly presented as recommendations in the 7th ACCP guidelines panel are found in this chapter. Specific new recommendations include 2.2.3 which recommends against routine coagulation monitoring in patients receiving LMWH (1C), except in those who are pregnant (1C) – although the recommendation for monitoring is dispute in the pregnancy chapter. A recommendation against routine monitoring is important as many clinical centers do not have routine access to anti-Xa heparin levels and, in some circumstances, this has served as a barrier to use of LMWH. A recommendation against routine monitoring should reassure centers that it is reasonable to use LMWH even if they cannot access such testing. The panel also suggests in 2.2.4 that obese patients receiving LMWH should be dosed by body weight (2C) – this is an important new recommendation since some regulatory authorities have imposed arbitrary dose caps despite a lack of evidence to support this practice. Although a weak recommendation, this statement should both reassure readers that dosing based on weight without regard for a cap is both reasonable and well within the “standard of practice”. However, the grade of recommendation (2C) does suggest that additional research in this area is required.

Oral anticoagulants (3): Oral anticoagulant therapy has evolved greatly in the last 20 years. A major advance in the care of anticoagulated patients has been the realization that optimal anticoagulant care requires a system of administration. Systems shown to produce improved anticoagulant care include organized expert anticoagulant clinics, and patient self testing and patient self monitoring. In each case, dosing is done by trained experts or computer systems. Recommendation 4.1.1 reflects this realization; a relatively strong recommendation (1B) is provided for systematic and coordinated processes to manage oral anticoagulant therapy, including patient education, systematic INR monitoring, tracking, follow up, and good communication with patient. The fact that patients can both monitor their own INR values, and use those values to predict warfarin doses is reflected in recommendation 4.3.1 which states that patient self monitoring should be considered where suitable (2B). In a recommendation that will, no doubt, engender controversy the panel has recommended that a trial of low dose oral vitamin K be considered in patients with variable INRs (2B, 2.5.1). Evidence supporting this recommendation is weak and the 2B recommendation may overstate the evidence supporting this therapeutic maneuver. That having been said, the level 2 recommendation does reflect the need for additional study and the fact that this recommendation may change based on the results of future research.

Interested readers are referred to the ACCP recommendations for additional information on new and modified recommendations. The 8th edition provides an Executive Summary of all major recommendations in Chapter 1 (4). Subsequently readers interested in additional information supporting the recommendations are advised read the relevant individual chapters.

Living with Post Thrombotic Syndrome (PTS)

Kelly Clark
NATF Patient Advocacy Committee

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It has been almost two years since I suffered my DVT and PE.  Since then I have experienced continual leg swelling and pain and have been diagnosed with the Post Thrombotic Syndrome, which is a long-term complication of DVT.  My legs will swell with just no reason or no specific event.  Sometimes it may even hurt to walk with the pain. 

Most patients are diagnosed with PTS within 2 years of suffering DVT.  However, it could take up to 5 years for some to develop the symptoms and signs of PTS.

The post thrombotic syndrome is caused by damage to the veins, causing a higher than normal venous blood pressure resulting in blood pooling and poor blood flow through the veins.  With poor blood flow, it can cause swelling, pain and even leg ulcers.  PTS can also cause serious long term problems, giving a poor quality of life. 

For myself, I have found that compression stockings as well as properly elevating my legs helps a great deal.  If I have a busy day and am unable to elevate my legs, I notice the swelling increasing more than if elevated.  PTS has changed my lifestyle since being on my feet for too long of a time is no longer an option.  I plan my days and times around how many hours I will be on my feet in order to try to prevent any symptoms from occurring. 

Symptoms and signs of post thrombotic syndrome:

1. Swelling
2. Pain
3. Cramping
4. Redness
5. Tingling or numbness sensation
6. Leg Ulcers

There is no specific treatment for PTS with the exception of wearing compression stockings, exercising, and elevating your legs and feet whenever possible.  You and your doctor can work out the best way for your own treatment.  The best treatment, in general, is to be proactive and listen to your body, and remaining therapeutic with any warfarin treatments you may still be taking. 

Electronic Alerts to Prevent DVT

Karen Fiumara, PharmD
Medication Safety Officer; Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of death, disability, and economic burden. VTE afflicts millions of individuals worldwide and accounts for several hundred thousand deaths annually in the United States. Few health care providers realize that the case fatality rate for PE, approximately 15 percent, exceeds the mortality rate for acute myocardial infarction.

Treatment of newly diagnosed VTE is difficult. Prevention is the best strategy. Fortunately, effective and safe prophylactic measures against VTE exist, and formal guidelines have been formulated and published (1-2). However, despite the endorsement of multiple medical societies and the adoption of guidelines as official hospital policy in many institutions, surveys demonstrate that implementation of VTE prophylaxis among high-risk patients continues to be suboptimal during hospitalization (3-4).

At Brigham and Women’s Hospital we have initiated a series of trials aimed at increasing prophylaxis by changing MD behavior and improving implementation of prophylaxis. We have utilized electronic computer generated alerts and a human alerts.

We have developed an electronic alert system, which is integrated with our Computerized Physician Order Entry (CPOE) system but functions independently. We created a risk score criteria by which the system determines the risk of DVT or PE for a particular patient. High risk patients were defined as having 4 or more score points, which could be accumulated with any of the following 8 VTE risk factors: cancer (3 points), prior VTE (3 points), hypercoagulability (3 points), major surgery (2 points), bed rest (1 point), advanced age (1 point), obesity (1 point), or hormone replacement therapy/oral contraceptives (1 point). All the information needed to calculate this risk assessment is stored in the computer system, allowing the process to run in an automated fashion. The system is programmed to generate an alert to the responsible physician and offer an opportunity to order appropriate prophylaxis for high risk patients.

As a quality improvement initiative, we undertook a trial in which high risk VTE patients without prophylaxis orders were randomized to an intervention or control group utilizing this system. The intervention was a single alert to the responsible physician that his or her patient is at high risk of DVT but does not have prophylaxis orders.

The control group patients had a high rate of symptomatic DVT or pulmonary embolism (PE): more than 8% during the 3 months of follow up. Each DVT or PE was confirmed by an imaging test, usually venous ultrasound or chest CT, respectively.

The intervention group had an overall 41% reduction in VTE. The rate of PE reduction was 60%. There was no increase in major or minor bleeding in intervention group. However, VTE prophylaxis was only prescribed for 33.5% of high-risk patients. After the study was published a multi-disciplinary team was convened consisting of physicians, pharmacists, nurses, research coordinators, and program developers to enhance the VTE alerts at BWH.

One of the major aims of enhancing was to engage house staff physicians in order to increase acceptance of the alert. We developed interactive techniques that were integrated into the design of the new alerts. Some of these included: providing the house staff with objective data that computerized alerts in this population decreased the incidence of VTE by 41% and creating an opportunity to capture the rationale for declining the alert. We also hypothesized that many house staff physicians may fear a risk of bleeding with pharmacological prevention. We therefore designed a final opportunity to order mechanical prophylaxis before allowing the user to exit the alert. The team also hypothesized that setting the alerts to generate at a consistent time during morning rounds and notification of the attending physician if action was not taken would increase acceptance. The enhanced VTE alerts generate at 8:30 AM each morning and the attending physician receives a text page 24 hours later if action is not taken.

The house staff physicians are first notified of a high-risk patient at the moment of login to the CPOE system. Once the user clicks on the alert, they are presented with multiple options. A physician may choose to review the alert details, which displays the patient specific criteria that qualified the patient as high-risk. The user is also presented with the results from the original study, access to the DVT prophylaxis order entry template, access to an on-line resource guide, or the option to exit.

The DVT prophylaxis template allows the user to select mechanical, pharmacological or a combination of prophylaxis measures. The on-line resource guide provides educational material that is up-to-date with clinical practice. If the user clicks the third option to exit to order entry, escape, or done options they are presented with a screen that prompts selection of a reason for declining the alerts. The reasons provided are patient is already receiving anticoagulants, the risk of bleed outweighs the benefit of anticoagulant therapy, patient is on comfort measures only, scheduled procedure, or other. The user must select a reason in order to proceed. Once a reason is selected, the user has the final opportunity to order mechanical prophylaxis via a second order entry template. The user is reminded that there is not an increased risk of bleeding with mechanical prophylaxis.

There is still considerable potential for electronic alerts to increase prophylaxis rates and reduce the rates of VTE. Our three-screen enhanced electronic alert study is aimed at improving physician response to the alert and determining the utility of opt out strategies to reduce the incidence of VTE.

North American Thrombosis Forum (NATF)

The North American Thrombosis Forum is a 501(c)(3) nonprofit organization that focuses on unmet needs and issues related to thrombosis and cardiovascular diseases such as deep vein thrombosis, pulmonary embolism, myocardial infarction, peripheral arterial occlusive disease, and stroke. The five areas of major focus are: 1) basic translational research, 2) clinical research, especially diagnosis and therapy, 3) prevention and education, 4) public policy, and 5) advocacy. NATF's legacy will be to improve patient care, outcomes, and public health by supporting thrombosis-related programs, such as novel research projects, innovative educational programs, public policy initiatives, regulatory issues and advocacy, and to broaden training opportunities for scientists and health professionals (physicians, nurses, pharmacists).

Our offices are located at 1620 Tremont Street, Suite 3022; Roxbury Crossing, MA 02120.  For general information, please call (617) 525-8326 or email: info@NATFonline.org .