UNDERUSE OF ORAL ANTICOAGULANTS LEAVES ELDERLY AT RISK FOR PULMONARY EMBOLISM
American Geriatrics Society Revises Clinical Practice Guidelines

NEW YORK--Older people have a heightened risk for systemic thromboembolism, pulmonary embolism (PE), and deep venous thrombosis (DVT), yet oral anticoagulant therapy--to prevent or treat these events--remains widely underused in this population. Why? Concern about the risks associated with anticoagulant therapy, primarily bleeding, and a lack of clear-cut guidelines regarding their use are two explanations.

To help address these issues, the American Geriatrics Society (AGS) Clinical Practice Committee recently published updated clinical practice guidelines for the use of oral anticoagulation in older people.[1] "The new guidelines are intended to clarify indications for the use of warfarin in the elderly and to assist physicians in the risk/benefit analysis of individual patients," said Laurie G. Jacobs, MD, in a recent interview with PULMONARY REVIEWS.

The revised guidelines include general recommendations for indications, dosing, monitoring, and reversal of anticoagulant therapy in patients age 65 years and older, based on findings from clinical trials. Factors associated with an increased risk for bleeding during treatment are also outlined in the report (Table 1).

"Compared with the original guidelines, which were published in 1995, the revised report provides more detailed information about the treatment of DVT; it also presents recommendations for the reversal of anticoagulation therapy," added Dr. Jacobs, who is the author of the guidelines and a member of the AGS Clinical Practice Committee. Since the publication of the original guidelines, more clinical data have become available to support recommendations in specific areas, such as atrial fibrillation, according to Dr. Jacobs, who is director of the division of geriatrics at Montefiore Medical Center and associate professor of clinical medicine at Albert Einstein College of Medicine, Bronx, NY.

INDICATIONS AND DOSING

"Warfarin tends to be underutilized … when there are indications for its use," said Charles A. Cefalu, MD, in a separate interview with Pulmonary Reviews. In general, pulmonologists tend to follow the guidelines more closely than primary care physicians, suggested Dr. Cefalu, who is also a member of the AGS Clinical Practice Committee. "Primary care physicians tend to underutilize warfarin, possibly because of concern about bleeding complications associated with the use of oral anticoagulation therapy," noted Dr. Cefalu, a professor of family medicine and associate chairman for geriatric program development at the Louisiana State University School of Medicine in New Orleans.

Anticoagulation is indicated for the prevention and treatment of DVT and PE in elderly patients undergoing hip surgery, total knee replacement, and major gynecologic surgery. Preventive treatment may begin several days preoperatively and should continue for at least three months or until the patient is ambulatory. Warfarin should be used to treat patients with proximal venous thrombosis, symptomatic calf vein thrombosis, and PE.

Initial proximal idiopathic venous thrombosis should be treated for six months, symptomatic calf vein thrombosis for at least three months, and recurrent thromboses indefinitely. The currently recommended duration of treatment for patients with PE is six months, although the optimum regimen has yet to be determined by randomized studies. An international normalized ratio (INR) between 2.0 and 3.0 is recommended; this range is considered to be as effective as more intensive regimens but is associated with less risk of bleeding.

Other potential candidates for treatment with oral anticoagulation include elderly patients who have mechanical prosthetic heart valves, as well as those with nonvalvular atrial fibrillation who are at increased risk for a blood clot to the brain, heart, or extremities, and patients with cardiomyopathy, valvular heart disease, and acute myocardial infarction. In most of these settings, an INR of 2.0 to 3.0 is preferred; however, in patients with mechanical valves, an INR of 2.5 to 3.5 should be sought.

The AGS guidelines recommend that warfarin be given for the first three months after insertion of a prosthetic heart valve and for one to three months post-myocardial infarction. Lifelong therapy is required for patients with atrial fibrillation, cardiomyopathy, or valvular heart disease.

In addition to the INR, several other factors should guide warfarin dosing, including the urgency of the need for anticoagulation; concurrent use of other anticoagulants, such as heparin or aspirin; potential drug interactions; and individual pharmacokinetic and pharmacodynamic factors. Close monitoring of patients taking warfarin is essential because a variety of factors can influence the dose-response relationship of this drug, including comorbid disease, age, and dietary fluctuations in vitamin K intake, according to Dr. Jacobs. For example, a fever may increase the intensity of anticoagulation in patients, she noted. Decreased dosing regimens should be considered in older people because they tend to have an increased sensitivity to warfarin. Finally, the guidelines recommend that patients with acute thrombotic diseases or thrombophilic disorders receive heparin and warfarin at therapeutic levels for two to four days.

WEIGHING THE RISKS

Although the AGS report offers recommendations to help guide physicians, the decision to use anticoagulant therapy should always be made on an individual basis and should take into account the clinical status of the patient, according to Dr. Jacobs.

Several factors may determine the risk for bleeding during treatment with oral anticoagulant therapy, including the intensity of anticoagulant effect, patient characteristics, use of other drugs that interact with oral anticoagulants, and duration of therapy. Bleeding complications occur more frequently in patients with venous thromboembolism and/or ischemic cerebrovascular disease, as well as during the first 90 days of therapy.

Whether advanced age is an independent risk factor for serious hemorrhage remains unclear. Nonvalvular atrial fibrillation is the only medical condition listed in the guidelines for which age is considered an independent risk factor for embolic events. Furthermore, noted Dr. Cefalu, "age should only be considered in the context of other factors in the patient's history, including previous stroke, gastrointestinal bleeding, and such comorbid conditions as severe anemia, myocardial infarction, and renal failure." He added that "you cannot separate the geriatric patient from the typical pulmonary patient with regard to this issue. I would weigh the risks and benefits of using warfarin for a high-risk patient who has had a pulmonary embolism or DVT. This also involves factoring in the patient's quality of life."

In some cases, such as in a patient who is age 80 years or older and who is at risk for falling, has dementia, and has a limited life expectancy, the use of oral anticoagulation may be inappropriate, suggested Dr. Cefalu. However, in other cases, warfarin may be quite beneficial for an older patient. "It's a clinical decision that can only be made after discussing the risks and benefits of warfarin therapy with the patient and family. You individualize your decision in all cases of clinical medicine, noting such factors as the patient's age, morbidity, [and] whether there is trauma [or] an increased risk of bleeding or liver disease."

TREATMENT REVERSAL

Special considerations are important in the perioperative setting because of the need to reverse anticoagulant therapy. For patients at low risk of thromboembolic events and for those who are scheduled for minor surgical procedures, oral anticoagulants can be discontinued several days preoperatively and surgery performed when the INR is less than 1.5. Vitamin K should not be given--or should only be given in small doses (eg, 1 mg to 2 mg)--to these patients, because it will prolong the time until warfarin can achieve a therapeutic level.

For patients at high risk of thromboembolism, treatment with heparin anticoagulation should be initiated as warfarin is discontinued before surgery. Daily monitoring of the INR is important, however, and patients should be admitted for intravenous heparin infusion when the INR is below 2.0. Surgery may be considered once the INR drops below 1.5; heparin should be discontinued four hours before surgery. Postoperatively, both heparin and warfarin should be reinstated as soon as possible; heparin can be discontinued once the INR is 2.0 or higher.

--Stu Chapman
--Deborah L. O'Connor

Reference
1. Clinical Practice Guidelines: The use of oral anticoagulants (warfarin) in older people. J Am Geriatr Soc. 2000;48:224-227.

Return to table of contents