Reducing the Risk of Warfarin-Related Hospitalizations
By Mark D. Coggins, PharmD, CGP, FASCP
Older adults are seven times more likely than younger adults to require hospitalization resulting from adverse drug events (ADEs), with nearly 100,000 such hospitalizations reported each year.1,2 With a growing older adult population in the United States and 40% of people over the age of 65 taking five to nine medications and 18% taking 10 or more,3 there is a tremendous need for increased coordination of efforts among patients, caregivers, and healthcare providers to effectively manage, monitor, and communicate pharmaceutical care issues to help minimize ADE risks, including hospitalizations.
The anticoagulant warfarin (Coumadin) accounts for 33% of reported ADE-related hospitalizations, with another one-third of these hospitalizations attributed to insulins (13.9%), oral antiplatelets (13.3%), and oral hypoglycemics (10.7%). Warfarin and antiplatelet hospitalizations are almost always a result of acute hemorrhages, with 71% of warfarin-related hospitalizations resulting from excessive doses. Nearly 94% of insulins and oral hypoglycemic medication ADE hospitalizations are a result of hypoglycemia.2 This suggests the need for improved education on diabetes treatment guidelines, including the need to minimize the use of sliding-scale insulin, which has long been shown to be a reactive approach to managing high blood sugars and is a practice that inadequately controls hyperglycemia, results in higher rates of hypoglycemia, and contributes to longer hospital stays.4
Therapy and Monitoring Goals
Warfarin is a narrow therapeutic medication requiring routine monitoring and dose adjustments. Prothrombin time (PT) is used to measure warfarin’s effectiveness and reflects the time it takes for clot formation to progress. PT values can vary between labs, depending on the thrombin sample used. The International Normalized Ratio (INR) is calculated from the PT to standardize values across labs. Higher INR values reflect a longer time required for blood clot formation with excessive dosing of warfarin resulting in higher INR values and increased risk of serious bleeding. Inadequate dosing results in lower INR values and a greater potential for fatal blood clots.
Most patients generally receive INR monitoring every two to four weeks; however, the recommended frequency of INR monitoring should be individualized and depends on numerous factors, including whether warfarin has recently been started or there have been recent dosage changes; whether the patient’s INR has been stable; the addition or removal of other medications known to interact with warfarin; dietary changes; and acute illness. Numerous drug interactions between warfarin and other medications are of great concern due to increased bleeding risks and may prompt the need for avoidance of the interacting medication, increased INR monitoring, or warfarin dosage reductions (see table 6 on page 10 for common warfarin drug interactions).
Managing Warfarin Bleeding Risk
Clinical Practice Guidelines
• Prescribers should use validated decision-support tools (paper nomograms or computerized dosing programs).
• Patients healthy enough to be treated as outpatients should receive a loading dose of 10 mg daily for two days, with warfarin dose adjusted based on INR. Some at-risk patients, such as the elderly, may need a loading dose of 5 mg or less.
• Patients with previously stable INRs with a single out-of-range INR of ≤ 0.5 below or above therapeutic range should continue the current dose and INR testing within one to two weeks.
• A therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) is preferred rather than a lower (INR < 2) or higher (INR 3.0 to 5.0) range.
• Patient self-management rather than usual outpatient INR monitoring is suggested for patients who are motivated and demonstrate competency in self-management strategies, including use of the self-testing equipment.
• Patients with stable INRs may require less frequent INR monitoring (ie, every three months).
A meta-analysis published in The Lancet supports self-monitoring and reported an associated reduced risk of blood clots (49%) in self-monitored patients without additional risks of bleeding complications. This report also noted that self-monitoring in very elderly patients has been shown to lower mortality without increased complications, as they are at high risk of major bleeding, suggesting that age should not be a factor in determining eligibility for self-management.6
— Mark D. Coggins, PharmD, CGP, FASCP, is the national director of clinical pharmacy services for more than 300 skilled nursing homes operated by Golden Living. He was recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award. He is a director-elect on the Board of the American Society of Consultant Pharmacists.
2. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365(21):2002-2012.
3. Slone Epidemiology Center at Boston University. Patterns of Medication Use in the United States, 2006: a Report From the Slone Survey. http://www.bu.edu/slone/SloneSurvey/AnnualRpt/SloneSurveyWebReport2006.pdf
4. Nau KC, Lorenzetti RC, Cucuzzella M, Devine T, Kline J. Glycemic control in hospitalized patients not in intensive care: beyond sliding-scale insulin. Am Fam Physician. 2010;81(9):1130-1135.
5. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S-184S.
6. Heneghan C, Ward A, Perera R, et al. Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet. 2012;379(9813):322-334.
Table 1: Common Dangerous Warfarin Drug Interactions
Table 2: Managing Elevated INRs5