Warfarin dose reduction vs watchful waiting for mild elevations in the international normalized ratio.
BACKGROUND
Whether clinicians should decrease the warfarin dose in response to a mild, asymptomatic elevation in the international normalized ratio (INR) is unknown.


OBJECTIVE
The study objectives were as follows: (1) to evaluate the safety of an anticoagulation service (ACS) policy advocating that the warfarin dose not be changed for isolated, asymptomatic INRs of < or = 3.4; (2) to compare the dosing strategies of an ACS and primary care providers (PCPs); and (3) to quantify the relationship between reduction of the warfarin dose and the subsequent fall in the INR.


METHODS
Randomized controlled study of health maintenance organization outpatients who were receiving warfarin.


METHODS
We identified 231 patients with a target INR of 2.5 and an isolated, asymptomatic INR between 3.2 and 3.4. Our ACS monitored 103 of the patients; PCPs monitored the remaining 128 patients.


METHODS
From all 231 patients, we obtained INRs and warfarin dosing history. From the 103 ACS enrollees, we also recorded adverse events.


RESULTS
One ACS patient had epistaxis in the 30 days after the elevated INR. Twenty-three percent of ACS enrollees and 47% of PCP patients reduced their warfarin dose (p < 0.001). The median follow-up INRs were similar in both cohorts: 2.7 in the ACS enrollees and 2.6 in the PCP patients. However, in a subgroup analysis of 190 patients who presented with an INR of 3.2 or 3.3, ACS enrollees were more likely to have a follow-up INR in the range of 2 to 3 (p = 0.03). The median follow-up INR was 2.7 in 148 patients who maintained their warfarin dose, 2.5 in 77 patients who decreased their dose by 1 to 20%, and 1.7 in 6 patients who decreased their dose by 21 to 43% (p < 0.001).


CONCLUSIONS
These findings support maintaining the same warfarin dose in asymptomatic patients with an INR of < or = 3.3, and reducing the dose for patients who have a greater INR or an increased risk of hemorrhage. Warfarin dose reductions > 20% should be avoided for mildly elevated INRs.
Banet
Gerald A
GA
Division of General Medical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Waterman
Amy D
AD
Milligan
Paul E
PE
Gatchel
Susan K
SK
Gage
Brian F
BF
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006279:Health Maintenance Organizations; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008923:Missouri; D019370:Observation; D012306:Risk; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D014859:Warfarin