Evaluation of Anticoagulation Initiation and Comparison of Low Versus High Warfarin Doses

dose in an attempt to reduce the time required to reach a therapeutic international normalized ratio (INR). However, initiating warfarin with large loading doses can potentially result in a number of complications. Loading doses of warfarin might increase the risk of elevated protimes and hemorrhage, especially in elderly patients who are often overly sensitive to warfarin.1 In addition, there is evidence that loading doses of warfarin might increase the risk of a transient hypercoagulable state at the initiation of warfarin therapy.2 Based on these potential problems associated with warfarin loading doses, recent clinical guidelines recommend initiating warfarin therapy at the average daily dose of 5 mg rather than administering loading doses of 7.5 to 10 mg.3 It has also been recommended that physicians consider initiating warfarin at doses of less than 5 mg in certain groups of individuals; for example: the elderly, patients with liver disease or impaired nutrition, patients with cardiac failure, individuals with low body weight, or those with bleeding diathesis.1,3 When a rapid anticoagulant effect is desired, heparin is often co-administered with warfarin. In these situations, guidelines recommend starting warfarin on the same day as heparin initiation and overlapping heparin therapy with warfarin for at least four to five days until an INR of 2 or more has been obtained on two consecutive days.4 Whether or not these guidelines are being instituted in actual clinical practice, however, is uncertain. Therefore, this study was conducted to evaluate the appropriateness of anticoagulation initiation in our facility and to further compare the therapeutic efficacy, clinical outcomes, and safety of low initial warfarin doses versus regimens with loading doses among hospitalized medical patients. Methods A retrospective chart review was conducted on inpatients started on warfarin at the VA Medical Center in Fargo, North Dakota. Study subjects were selected from a computer-generated report of patients discharged from the hospital between September 1998 and April 2001 with the primary diagnosis of atrial fibrillation (A-fib), deep vein thrombosis (DVT), pulmonary embolism (PE), or Q-wave myocardial infarction (MI). Patients were excluded if they had been on warfarin prior to admission or if an interacting drug had been started after initiation of warfarin therapy. Initial and subsequent warfarin dosing was at the discretion of the physician. Patients were assigned to low and high initial warfarin dose groups. The low-dose group consisted of patients who had received an initial warfarin dose of 5 mg or less, and the high-dose group was composed of patients who had received an initial warfarin dose greater than 5 mg. Baseline and subsequent INRs and hemoglobin levels were recorded for each patient. Heparin duration and length of stay were also determined. The day that warfarin was started in relationship to heparin initiation was also recorded. Other demographic information collected included age, weight, type of heparin therapy (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or none), and concurrent medications. Assessment of therapeutic efficacy was based upon the mean time to reach a first therapeutic INR, and the mean time to reach two consecutive therapeutic INRs. The time to reach a therapeutic INR was defined as the number of days required to obtain an INR between 2 and 3 with day one recorded as the day after the first dose of warfarin. In addition, mean length of heparin duration and hospital stay (from time of anticoagulation start until discharge) were recorded. Clinical outcome was measured by recurrence rate of any thromboembolic event within three months following warfarin initiation. Evaluation of Anticoagulation Initiation and Comparison of Low Versus High Initial Warfarin Doses