The Impact of Inpatient Versus Outpatient Initiation on Early Warfarin Dosing

Abstract

Background and Objectives Dosing algorithms for warfarin incorporate clinical and genetic factors but may not account for the numerous comorbidities affecting patients who start warfarin while hospitalized. We aimed to determine whether these algorithms perform differently when warfarin is initiated for inpatients compared with outpatients. Patients and Methods We analyzed a prospective cohort of 1015 participants from the Clarification of Optimal Anticoagulation through Genetics (COAG) trial who were randomized to either pharmacogenetically or clinically guided warfarin dosing algorithms. Clinicians and participants were blinded to dose during the first 28 days. We compared groups, based on location at the time of the first warfarin dose request, in relation to the following outcomes: percentage of time in the therapeutic international normalized ratio (INR) range (PTTR) during the first 4 weeks, time to first therapeutic INR, time to maintenance dose, and the difference between predicted and observed maintenance doses. Results A total of 527 participants started warfarin as inpatients and 488 as outpatients. There was no difference in PTTR based on location: 43.2 % for inpatient versus 47.4 % for outpatient initiation [mean adjusted difference −2.2 %; 95 % confidence interval (CI) −5.9 to 1.6]. Similarly, there were no differences in time to first therapeutic INR [hazard ratio (HR) 1.06; 95 % CI 0.91–1.24] or to maintenance dose (HR 0.96; 95 % CI 0.81–1.14). There was no evidence of interaction between study intervention (pharmacogenetically vs. clinically guided therapy) and location of initiation for these main outcomes. The difference between predicted and observed maintenance doses was similar for both locations. Conclusion The warfarin dosing algorithms performed similarly for subjects who initiated warfarin as inpatients and outpatients, regardless of whether dosing was pharmacogenetically or clinically guided.

Review of Warfarin; A Cytochrome P450 Metabolizing Drug, in Clinical Practice

“…A study of dosing algorithms comparing inpatients with outpatients showed similarities irrespective of whether dosing was pharmacogenetically or clinically guided (20). Studies confirm the need for more systematic patient instruction at the time of targetspecific administration of oral anticoagulants (TSOACs) and further maintenance therapy (19).…”

“…The warfarin dosing algorithms were similar for individuals who started warfarin as inpatients and outpatients, irrespective of whether dosing was pharmacogenetically or clinically conducted (20). The risk of hemorrhage is higher in overweight as compared to normal weight patients who are on warfarin.…”

“…The action of warfarin may constantly be inverted by vitamin K 1 , as the blood cannot be coagulated directly. After prescription, warfarin necessitates two to three days for onset of effective treatment in which the duration of the effect of a single dose is about two to five days (1)(2)(3)(4)(5)(6)(7)(14)(15)(16)(17)(18)(19)(20)(21)(22) Spontaneous spinal subdural hematoma is reported at a rare level in those receiving anticoagulant or antiplatelet agents (11). However, a great frequency of intracerebral hemorrhages with multiple cerebral microbleeds has been reported in warfarin-treated patients (12).…”