US Pharm. 2010;35(2):20-22.
Data indicate that substantial patient morbidity and mortality occur as a result of hospital medication-related errors; deaths per year are estimated at between 40,000 and 100,000.1 Adverse drug events (ADEs) total approximately 20% of all adverse events (AEs) in hospitals and are the greatest cause of nonoperative AEs.2 In nursing homes, medication-related injuries are common and are often preventable.1 In an attempt to decrease errors that cause AEs and provide optimal pharmaceutical care for patients, these data serve as an impetus for systemwide internal review and reform.1,3 As of January 2009, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) expects full compliance with the National Patient Safety Goal (NPSG) 03.05.01 to maintain accreditation status. This goal focuses on reducing the likelihood of patient harm associated with the use of anticoagulant therapy.4 This column will address elements of warfarin anticoagulation, particularly in seniors; it aims to encourage pharmacists to embrace the recommended safety goal and consider adapting the example policy, protocol, and monitoring form to their various practice settings to reduce the likelihood of harm associated with warfarin therapy.
Warfarin: Risk for Frequent ADEs
The use of warfarin anticoagulation is indicated for prophylaxis and treatment of thromboembolic disorders (e.g., venous, pulmonary) and embolic complications secondary to atrial fibrillation or cardiac valve replacement.5 After patients experience a myocardial infarction (MI), warfarin is used as an adjunct to reduce the risk of systemic embolism (e.g., recurrent MI, stroke).5 While warfarin has the ability to decrease mortality, it is often inappropriately prescribed in seniors and is associated with serious and frequent ADEs in both inpatients and outpatients.1,6 Interestingly, despite residing in a setting with supervision, residents of long-term care facilities have been subject to the underuse of beneficial warfarin therapy.7 Many seniors, including those in the acute-care hospital setting, are found to have international normalized ratio (INR) values well below or above normal.
Are the INRs being monitored based on the appropriate range for a specific indication for use? For example, is the patient with a mechanical prosthetic heart valve being monitored for a goal INR of 2.5 to 3.5 to prevent systemic embolism as compared with a goal INR of 2 to 3 for the post–MI patient or patient with atrial fibrillation? 8 Is the indication for use of warfarin clearly documented with the appropriate corresponding goal INR and is this information accessible to all health care professionals involved in the monitoring process? Is the medication regimen regularly reviewed to identify, resolve, and prevent drug–drug interactions that may potentiate an increase or decrease in the INR (TABLE 1)? These are just some of the relevant questions pharmacists should be familiar with regarding warfarin therapy in light of the fact that anticoagulants have been found to be one of the most common medications associated with preventable ADEs in seniors.1
Seniors: At Risk for AEs
Seniors, as a population of individuals over the age of 65 years, are considered one of the groups of patients at greatest risk of warfarin-related bleeding (e.g., gastrointestinal bleed, intracerebral hemorrhage).9,10 Other groups appearing at greatest risk include patients with a history of gastrointestinal bleeding or stroke and patients with comorbidities such as anemia (hematocrit <30%), diabetes, recent MI, and renal insufficiency (serum creatinine >1.5 mg/dL).9 Other identified risk factors for bleeding include liver disease, dementia or cognitive impairment, and medications such as antiplatelet agents and nonsteroidal anti-inflammatory drugs.10 Additionally, increased age has been associated with a risk of complications secondary to bleeding.5
Warfarin has a long half-life elimination (range: 20-60 hours; mean 40 hours) that is highly variable among individuals.5 The reversal to normal clotting status may be slower in senior patients as compared with younger individuals and must be considered if warfarin must be stopped (e.g., prior to surgery).11 The presence of comorbidities and their corresponding medication regimens, common among elderly patients, may also increase and/or decrease INRs due to multiple drug interactions; OTC products including herbal and nutritional products should not be overlooked. It is recommended that patients with impaired nutritional status receive reduced initial dosing of warfarin.8 Vitamin K is involved in the formation of coagulation factors.9 Educating patients and family/caregivers on the selection of foods low in vitamin K is essential for outpatients and even for inpatients when low vitamin K diets are not readily available and the patient needs to comply with appropriate menu item selection.8
AEs: Impact on Prescribing
Not surprisingly, it has been reported that a patient’s bleeding events secondary to warfarin therapy can influence the prescribing of warfarin.10 Choudhry et al explored the impact of AEs on prescribing warfarin in patients with atrial fibrillation.10 This database study in Ontario, Canada, was a population-based, matched-pair, before-and-after analysis. The researchers sought to quantify the influence of physicians’ experiences with AEs in patients with atrial fibrillation who were treated with warfarin.10 The participants of the study were physicians who were treating patients with atrial fibrillation admitted to the hospital for the following AEs: 1) thromboembolic strokes while not taking warfarin; and 2) major hemorrhage while taking warfarin.10 Also selected were pairs of other patients with atrial fibrillation treated by the same physicians.10 The researchers concluded that a physician’s experience with bleeding events secondary to warfarin (e.g., major hemorrhage) can influence the prescribing of warfarin; they also noted that AEs possibly associated with the underuse of warfarin (e.g., thromboembolic stroke) may not affect subsequent prescribing.10
There are many challenges faced by clinicians who manage anticoagulation therapy for their patients (TABLE 1). According to Rochon and Gurwitz, optimizing medication therapy means achieving the balance between overprescribing of inappropriate therapy and underprescribing of beneficial therapy.7
Use of Triggers to Detect ADEs
Hartis et al describe automating the identification of potential and actual ADEs in the case of warfarin anticoagulation through a trigger-based approach.3 The researchers recommend using automated triggers provided by laboratory and pharmacy data. Specifically, they note that INRs >3.0 and vitamin K administration appeared to be reliable indicators of warfarin-associated ADEs.3 A reliable surveillance system allows a physician the opportunity to modify the warfarin therapy and potentially cease the progression of a mild or moderate ADE to a more severe condition.12 Hartis et al concluded that detection with these indicators appeared to reduce ADEs when combined with appropriate interventions such as staff education and real-time adjustments in therapy.3
National Patient Safety Goal.03.05.01
When a high-risk medication such as warfarin is warranted, standardized guidelines for use can help ensure that clinicians are managing the medication in a safe and consistent manner.13 Using standardized practices in conjunction with patient involvement can decrease the risk of ADEs associated with the use of anticoagulants (e.g., unfractionated heparin, low-molecular-weight heparin, warfarin).4
Finks et al, also known as The Mid-South College of Clinical Pharmacy (MSCCP) Task Force on anticoagulation, were charged with 1) identifying practice variations regarding NPSG.03.05.01; 2) establishing professional collaboration to share policy and protocol development; and 3) facilitating the institutions to meet the JCAHO compliance deadline. The task force was comprised of pharmacy administrators, clinical pharmacy practitioners, and pharmacy faculty from local hospitals within the greater Memphis, Tennessee, area.8 Input was based on different clinical settings and varying levels of experience from multiple institutions. Pharmacists can be certain that institutions large and small can benefit from the collaborative approach of the MSCCP Task Force on anticoagulation. A practice report has recently been published (see Reference 8) and pharmacists will find the examples (e.g., warfarin policy, protocol, monitoring form; see Resources for the Pharmacist) and components (TABLE 2) of an anticoagulation management program helpful to utilize and tailor to their facility’s needs, based on their own staffing and resources. Pediatric issues are also included in the report.8 Finks et al report that “pharmacists are well suited to monitor patients on anticoagulation therapy and are vital to reducing medication errors and improving the care of patients receiving these regimens.”8
Warfarin has been found to be one of the most common medications associated with preventable ADEs in seniors. Pharmacists are important and necessary team players in the reduction of medication errors and improvement of patient care. Even if a pharmacist’s current practice setting does not lend itself to a formalized anticoagulation program, becoming apprised of the safety benefit of standardized practices in the management of warfarin therapy will surely inspire and encourage pharmacists to raise the standard of their current practice to reduce the risk of harm in vulnerable seniors and others.
1. U.S. National Institutes of Health. National Institute on Aging. Adverse drug events in nursing homes: common and preventable. www.nia.nih.gov/NewsAndEvents/PressReleases/PR20000809Adverse.htm. Accessed January 5, 2010.
2. Thomas EJ, Studdert DM, Burstin HR, et al. Incidence and types of adverse events and negligent care in Utah and Colorado. Med Care. 2000;38:261-271.
3. Hartis CE, Gum MO, Lederer JW Jr. Use of specific indicators to detect warfarin-related adverse events. Am J Health-Syst Pharm. 2005;62:1683-1688. www.medscape.com/viewarticle/510611_6. Accessed January 5, 2010.
4. The Joint Commission. Accreditation Program: Hospitals. National Patient Safety Goals. www.jointcommission.org/NR/rdonlyres/31666E86-e7f4-423e-9be8-f05bd1cb0AA8/0/hap_npsg.pdf. Accessed January 15, 2010.
5. Semla TP, Beizer JL, Higbee MD. Geriatric Dosage Handbook. 14th ed. Hudson, OH: Lexi-Comp, Inc; 2009:1725-1730.
6. Kanjanarat P, Winterstein AG, John TE, et al. Nature of preventable adverse drug events in hospitals: a literature review. Am J Health-Syst Pharm. 2003;60:1750-1759.
7. Rochon PA, Gurwitz JH. Medication use. In: Hazzard WR, Blass JP, Halter JB, et al, eds. Principles of Geriatric Medicine and Gerontology. 5th ed. New York, NY: McGraw-Hill, Inc; 2003:224-225.
8. Activities of Memphis-area hospitals to meet National Patient Safety Goals for warfarin therapy. Am J Health-Syst Pharm. 2009;66:2179-2188.
9. Beers MH, Porter RS, Jones TV, et al. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2006:420,759-760,2514-2520,2533-2545.
10. Choudhry NK, Anderson GM, Laupacis A, et al. Impact of adverse events on prescribing warfarin in patients with atrial fibrillation: matched pair analysis. BMJ. 2006 January 21;332:141-145.
11. Beers MH, Berkow R, eds. The Merck Manual of Geriatrics. 3rd ed. Whitehouse Station, NJ: Merck & Co.;2000:60-61,70-71.
12. Evans RS, Pestotnik SL, Classen DC, et al. Preventing adverse drug events in hospitalized patients. Ann Pharmacother. 1994;28:523-527.
13. Fairview Southdale Hospital, Edina, MN. Anticoagulation guidelines. www.ihi.org/IHI/Topics/PatientSafety/MedicationSystems/Tools/AnticoagulationGuidelines.htm. Accessed January 5, 2010.
14. Li J, Wang S, Barone J, et al. Warfarin pharmacogenomics. Pharmacy and Therapeutics.
15. Zagaria ME. Future technology for warfarin therapy. US Pharm. 2007;32(3):34-38. 2009;34:422-427.
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