Assessing evidence of interaction between smoking and warfarin: A systematic review and meta-analysis

Nathisuwan, Surakit, Dilokthornsakul, Piyameth, Chaiyakunapruk, Nathorn, Morarai, Tatiya, Yodting, Thararat and Piriyachananusorn, Nichakorn (2011) Assessing evidence of interaction between smoking and warfarin: A systematic review and meta-analysis. Chest, 139 5: 1130-1139. doi:10.1378/chest.10-0777

Author Nathisuwan, Surakit
Dilokthornsakul, Piyameth
Chaiyakunapruk, Nathorn
Morarai, Tatiya
Yodting, Thararat
Piriyachananusorn, Nichakorn
Title Assessing evidence of interaction between smoking and warfarin: A systematic review and meta-analysis
Journal name Chest   Check publisher's open access policy
ISSN 0012-3692
Publication date 2011-05-01
Sub-type Article (original research)
DOI 10.1378/chest.10-0777
Volume 139
Issue 5
Start page 1130
End page 1139
Total pages 10
Place of publication United States
Publisher American College of Chest Physicians
Collection year 2012
Language eng
Formatted abstract
Chronic smoking, theoretically, can interfere with warfarin metabolism through enzyme-inducing effects of polycyclic aromatic hydrocarbons. However, clinical evidence of interactions between warfarin and smoking are inconclusive. This study aimed to systematically review all relevant clinical evidence of this interaction.


We performed a systematic search using computerized databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Allied and Complementary Medicine, PsycINFO, International Pharmaceutical Abstracts, and from 1966 to December 2008. Keywords included "warfarin" with "smoking," "tobacco," "cigarette," and "polycyclic aromatic hydrocarbons." Original articles reporting interaction between warfarin and smoking were included. All articles were reviewed independently by two investigators for study design, population, outcomes, and quality of evidence.

Of the 1,240 studies retrieved, one experimental pharmacokinetic study and 12 crosssectional studies were included. The pooled analyses of multivariate studies suggested that smoking was associated with a 12.13% (95% CI, 6.999-17.265; P<.001) increase in warfarin dosage requirement and an additional 2.26 mg (95% CI, 2.529-7.042; P=5.355) per week compared with nonsmoking. Additional sensitivity analysis of four multivariate studies with adjustment for pharmacogenomic factors suggested that smoking was associated with a 13.21% (95% CI, 8.59%-17.83%; P<.001) increase in warfarin dosage requirement compared with nonsmokers. Results of an experimental pharmacokinetic study lend theoretical support to the findings.

Evidence suggests that smoking may potentially cause significant interaction with warfarin by increasing warfarin clearance, which leads to reduced warfarin effects. Close monitoring of warfarin therapy should be instituted when there is a change in smoking status of patients requiring warfarin therapy.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Public Health Publications
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Created: Tue, 06 Sep 2011, 15:28:52 EST by Geraldine Fitzgerald on behalf of School of Public Health