Oral AnticoagulantsOral anticoagulants: Pharmacologic issues for use in the elderly
Section snippets
Mechanism of Action
Warfarin and other coumarin derivatives act by inhibiting the action of vitamin K in the gamma carboxylation of glutamic acid residues on coagulation factors II, VII, IX, and X. Without gamma carboxylation, these proteins cannot participate in coagulation. Warfarin binds to the liver microsomal enzyme, vitamin K 2,3-epoxide reductase, and thereby inhibits the cyclic production of the reduced form of vitamin K. Reduced vitamin K is a necessary cofactor in the carboxylation of the vitamin
Quality of Anticoagulation Control in the Elderly
Although physicians often cite erratic control as a reason not to prescribe anticoagulants in their elderly patients, there are little published data to support this fear. In a recent study of oral anticoagulant treatment, 461 patients 75 years of age and older were compared with 461 control patients aged less than 70. Time spent within the therapeutic range was 71% versus 71.9%, and time spent above the range was 5.3% versus 5.5%. The mean interval between tests was 17.1 days versus 17.3 days.
Laboratory Assessment of Anticoagulant Intensity
The intensity of anticoagulation is measured with the prothrombin time test and expressed as the ratio of the patient's prothrombin time to the laboratory's control (prothrombin time ratio). Standardization of the prothrombin time ratio across laboratories is necessary to account for the different sensitivities of the various thromboplastin reagents used in the assay. The INR has replaced the prothrombin time ratio as the universally accepted measurement of anticoagulation intensity.68 To
Assessing Warfarin Candidacy
There are no existing data to suggest that age itself constitutes a specific contraindication to oral anticoagulants. Before initiating any discussion on the risks and benefits of warfarin therapy, a thorough assessment of patient-specific factors that might increase the hazards related to warfarin needs to be conducted. Evaluation and documentation of the patient's cognitive function, fall risk, nutritional status, alcohol use, patterns of medical compliance, and overall health are
Summary
There has been a marked expansion of the indications for oral anticoagulant therapy, particularly among the elderly. Despite the documented benefits, the use of warfarin remains strikingly low among patients 80 years of age and older. Elderly patients often exhibit an enhanced dose response to warfarin. On average, steady-state warfarin doses decrease by 11% per decade of age. Pharmacokinetic changes in the elderly are negligible. Pharmacodynamic differences have not been well characterized.
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2016, European Geriatric MedicineCitation Excerpt :Nonetheless, anticoagulants remain underused in many settings due to the inherent difficulty in warfarin monitoring and dosing, or administration of subcutaneous drugs [16,17]. Warfarin use in the elderly population raises, in addition, a series of specific issues: drug and food interactions (which are particularly relevant in the elderly due to polymedication), restrictions associated with comorbidities, inadequate anticoagulation control (due to mobility problems and lack of family/social support), and increased fall risk [16,18,19]. An array of novel drugs was introduced in recent years, mainly in the anticoagulation area, where the available therapeutic options did not met the underlying needs in AF and particularly in the elderly [4,20–22].
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2011, American Journal of MedicineCitation Excerpt :Our findings in elderly inpatients are in agreement with these results obtained in nonelderly outpatients showing that low-dose vitK1 was more effective in returning INRs to the treatment range than simply withholding warfarin.26,27 This effect of vitK1 is valuable, as prolonged exposure to risky INRs may increase the risk of bleeding, especially in the elderly.28 Of note, in the new ACCP guidelines issued in 2008, administration of oral vitK1 in patients with mild to moderately elevated INRs without significant bleeding is now a grade 1A recommendation (ie, strong recommendation, high-quality evidence).9
Address reprint requests to, Elaine M. Hylek, MD, MPH, General Internal Medicine Division, Clinical Epidemiology Unit, Massachusetts General Hospital, 50 Staniford Street, 9th Floor, 923, Boston, MA 02114
This article was supported by the Robert Wood Johnson Generalist Physician Faculty Scholar Award.