Transcript Journal Club

Interaction between
acetaminophen and warfarin in
adults receiving long-term oral
anticoagulants: a randomized
controlled trial
นศภ.ณัฐวุฒ ิ
ดวงแดง
มหาวิทยาลัยเชียงใหม่
่
นสภ.จตุพร
ใจเคลือน
มหาวิทยาลัย
พะเยา
นสภ.อ ังสนา เพ็ญสมบู รณ์
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impact factor
= 2.743
Abstract
Introducti
on
 The mean INR increase in
patients receiving
acetaminophen at the
highest recommended
dosage (4 g/day)
 No prospective study has
Research
 Acetaminophen
questions given at 2
g/day and
3 g/day might potentiate the
anticoagulant
effect of warfarin
Object
ive
 To evaluate the effect of
acetaminophen, given at 2
g/day and 3 g/day, on INR
in stable patients treated
with warfarin
Study Design
 randomized, parallel
(three arms), doubleblind, placebo-controlled
study
Inclusion
criteria
 Patients treated with
warfarin (target INR 2 to
3) stable anticoagulation
at
2 to 9 mg for more than
30 days
 Aged 18 years or older
Exclusion
criteria
 Any treatment change
within 7 days before
enrollment
 Any paracetamol intake
within the last 14 days
 St John's wort treatment
Exclusion
criteria
 Drug allergy Concomitant
drug
( 5fluorouracile, acetylsalicylic
acid, non steroidal antiinflammatory drugs,
chloramphenicol, diflunisal,
miconazole)
Drop out
 INR value were higher
than 3.5
 Drug known to interact
with warfarin or
acetaminophen
Method
45 Patients
Control group
Experimental
(9)
group (36
Placebo (9)
Acetaminophen
2 g/day (18) 3 g/day
(18)
Method
Placebo
2 g/day
3 g/day
two placebo tablets
three times a day
two 500 mg tablets twice a d
+ two placebo tablets once d
two 500 mg tablets
three times a day
Outcome
 Primary outcome
- The mean maximum increase in
INR from
baseline to Day 10
 secondary outcome
- The mean maximum INR
- Day 10 - Day 1 differences in
factors II, V, VII, AT-III plasma
Outcome
 secondary outcome
- Day 10 - Day 1 differences in
acetaminophen plasma
concentration between groups
- Day 10 - Day 1 differences in R(), S(-)warfarin
plasma
concentrations between groups
- Day 10 - Day 1 differences in
Statistics
Sample size and percent drop out
There are 45 pt. in these study.
- intra-individual INR variability is 0.3
- expected INR increase of at least 0.5
- bilateral α level of 5% และ β level of 10%
-No drop out
Statistics
มเหมาะสมของสถิตท
ิ ใช้
ี่ กบ
ั ชนิ ดของตัวแปร
- ANOVA
-post-hoc test
-All statistical analyses were implemented by
using Statview v8.0 (SAS Institute, Cary, NC, USA)
- Results were expressed as mean and 95%
confidence interval (CI), or as a percentage, as
appropriate. A P value of 0.05 or less indicated
statistical significance
Result
Result
Fig. 1 Correlation between INR
changes and
Result
Fig. 2 Correlation between INR
changes and factors II plasma
Result
Fig. 3 Correlation between INR
changes and factors VII plasma
Limitation of
Research
 The lack of variables
follow up after withdrawal
of acetaminophen
 The unexpected imbalance
observed in the
randomization of the
population regarding age,
Conclusion
- Acetaminophen, 2 g/day and 3
g/day
significantly increased the INR
in patients
treated with warfarin
- Recommend close INR
monitoring in patients
Generalizab
ility
- European pt. -> Genetics variation
- Life style and environment
- Other drugs and agents
- Disease
Thank
you