Warfarin Anticoagulation in Older Adults: A Review of Outpatient Initiation and Monitoring
Warfarin reduces the risk of thrombotic complications in a wide range of patients and appears to be particularly effective in older adults. Warfarin initiation should be undertaken with care in the older adults because they are likely to require smaller maintenance doses to achieve the same target international normalized ratio (INR). Inappropriate prescribing of medications among older adults increases the risk of drug interactions that may alter warfarin anticoagulation. Such interactions should be anticipated and monitored to ensure that over- or under-anticoagulation do not persist. A range of strategies are available to follow warfarin therapy in the outpatient setting to ensure safe and effective anticoagulation.
Key words: warfarin, anticoagulation, vitamin K, atrial fibrillation.
Introduction
Warfarin anticoagulation is challenging. Its clinical efficacy is dependent on maintaining anticoagulation within a narrow therapeutic window; its dose response is variable and influenced by other drugs and diet; and supratherapeutic anticoagulation carries a significant risk of bleeding, which can be fatal. Despite these challenges, the number of aging individuals who are candidates for warfarin therapy is increasing, due in large part to the increased prevalence of atrial fibrillation with increasing age.1 Atrial fibrillation affects approximately 10% of individuals ≥ 80 years of age.2 Warfarin therapy reduces the risk of stroke in a broad subset of patients with atrial fibrillation by 68%,3 and the benefit of anticoagulation is greatest among patients greater than 75.4,5 Despite this evidence, warfarin use in patients > 80 years remains low at 12-24%, even after adjusting for contraindications to anticoagulation (Table 1).6,7 Risk of hemorrhage and erratic control are frequently cited reasons for physicians not prescribing anticoagulants to geriatric patients.8 Optimal anticoagulation control in the older population, as with any patient group, is facilitated by physician appreciation of the challenges and evidence in support of oral anticoagulant therapy. This review will focus specifically on initiating and monitoring warfarin therapy in the outpatient setting.
Pharmacology and Monitoring
Warfarin, along with other Coumarin derivatives, produces its anticoagulant effect through a reduction in the vitamin K-dependent coagulation factors II, VII, IX, and X (Figure 1). The prothrombin time (PT) test, which reflects warfarin’s reduction of factors II, VII, and X at a rate proportional to their respective half-lives, is used to monitor warfarin anticoagulation. During the first several days of warfarin therapy, the PT reflects mainly a reduction of factor VII with its half-life of only six hours. Since 1982, the international normalized ratio (INR) has been used to standardize the reporting of PT results and to account for variability in local thromboplastin reagents used in the test. Therapeutic anticoagulation is achieved by titrating the dose of warfarin to reach a target INR range, which for most indications is between 2.0 and 3.0 (Table 2).
Initiation and Maintenance Dosing
The effect of warfarin on the PT is seen within the first two to three days of therapy; however, onset of therapeutic anticoagulation is delayed for several days while factors II and X decline at a rate proportionate to their half-lives.9 This disassociation between the INR and true anticoagulation early in therapy may account for early recurrences of thrombosis in patients treated for acute deep vein thrombosis who do not receive heparin.10 The urgency with which anticoagulation is required determines the strategy for warfarin initiation.