The influence of patient adherence on anticoagulation control with warfarin: results from the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study.
BACKGROUND
Warfarin sodium is a highly efficacious drug, but proper levels of anticoagulation are difficult to maintain. Conflicting data exist on the influence of patient adherence on anticoagulation control.


METHODS
We performed a prospective cohort study at 3 anticoagulation clinics to determine the effect of adherence on anticoagulation control. Patients treated with warfarin with a target international normalized ratio of 2.0 to 3.0 were monitored with electronic Medication Event Monitoring System (MEMS) medication bottle caps. Detailed information was collected on other factors that might alter warfarin response.


RESULTS
Among 136 participants observed for a mean of 32 weeks, 92% had at least 1 missed or extra bottle opening; 36% missed more than 20% of their bottle openings; and 4% had more than 10% extra bottle openings. In multivariable analyses, there was a significant association between underadherence and underanticoagulation. For each 10% increase in missed pill bottle openings, there was a 14% increase in the odds of underanticoagulation (P<.001); participants with more than 20% missed bottle openings (1-2 missed days each week) had more than a 2-fold increase in the odds of underanticoagulation (adjusted odds ratio, 2.10; 95% confidence interval, 1.48-2.96). Participants who had extra pill bottle openings on more than 10% of days had a statistically significant increase in overanticoagulation (adjusted odds ratio, 1.73; 95% confidence interval, 1.09-2.74).


CONCLUSIONS
Patients have substantial difficulties maintaining adequate adherence with warfarin regimens, and this poor adherence has a significant effect on anticoagulation control.
Kimmel
Stephen E
SE
Department of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 423 Guardian Drive, Philadelphia, PA 19104, USA. skimmel@cceb.med.upenn.edu
Chen
Zhen
Z
Price
Maureen
M
Parker
Catherine S
CS
Metlay
Joshua P
JP
Christie
Jason D
JD
Brensinger
Colleen M
CM
Newcomb
Craig W
CW
Samaha
Frederick F
FF
Gross
Robert
R
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010349:Patient Compliance; D011446:Prospective Studies; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin