Patient factors against stable control of warfarin therapy for Japanese non-valvular atrial fibrillation patients.
BACKGROUND
Effectiveness and safety of warfarin therapy for non-valvular atrial fibrillation (NVAF) patients are strongly associated with its stability presented such as time in therapeutic range (TTR) of PT-INR. However, the factors that affect TTR have not been fully elucidated in Japan where majority of patients are controlled within the range of 1.6-2.6 of PT-INR irrespective of the age.


METHODS
We retrospectively analyzed 163 NVAF patients taking warfarin to determine the factors that affect TTR including metabolic enzymes polymorphisms after TTR calculation with both the standard PT-INR range and the actual control range of 1.6-2.6.


RESULTS
Overall TTR calculated using Japanese Guideline was 69.7 ± 25.1% (<70 and ≥ 70 years; 49.6 ± 24.8% and 77.8 ± 20.3%, respectively). After confirming that PT-INR values in patients < 70 years distributed in the same range as in those ≥ 70 years, as in a Japanese large cohort, we recalculated TTR of those < 70 years with 1.6-2.6 of PT-INR and found that it was 79.5 ± 20.1%. Poor control of this new TTR were significantly associated with the lower height, the higher serum creatinine, the lower creatinine clearance, female gender, and presence of congestive heart failure, (p<0.05 respectively). Multivariate analysis revealed female gender and presence of congestive heart failure as independent predictor of the lower TTR (p<0.05, p<0.01, respectively). Polymorphism of CYP2C9 and VKORC1 were related to the dosage of warfarin but not determinant of TTR.


CONCLUSIONS
When evaluated using a range of PT-INR actually used in Japan, TTR is generally well controlled and female gender and presence of congestive heart failure significantly affected the poorer TTR control.
Division of Cardiology, Shimada Hospital. Electronic address: hidetomi@zc5.so-net.ne.jp.
Hideharu
H
Tomita
Toshiaki
T
Kadokami
Hidetoshi
H
Momii
Natsumi
N
Kawamura
Masayoshi
M
Yoshida
Tetsuji
T
Inou
Yutaka
Y
Fukuizumi
Makoto
M
Usui
Kouta
K
Funakoshi
Satoshi
S
Yamada
Tohru
T
Aomori
Koujiro
K
Yamamoto
Tsukasa
T
Uno
Shin-Ichi
S
Ando
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
Non-valvular Atrial Fibrillation; Time in therapeutic range; Warfarin