Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis.
OBJECTIVE
To determine the risk of bleeding and supratherapeutic international normalized ratios (INRs) associated with use of complementary and alternative medicine (CAM) in patients receiving warfarin.


METHODS
Prospective, longitudinal study.


METHODS
An acute care, academic and research hospital in Canada.


METHODS
A total of 171 adults who were prescribed warfarin anticoagulation therapy for an expected duration of at least 4 months after enrollment.


METHODS
Patients were asked to complete a 16-week diary by recording bleeding events and exposure to factors previously reported to increase the risk of bleeding and supratherapeutic INRs, including CAM consumption.


RESULTS
Prescription, medical, and laboratory records were reviewed. Risk factors for bleeding events and supratherapeutic INR (at least 0.5 units above the target range) were evaluated longitudinally by using generalized estimating equation (GEE) modeling. Of the 171 patients completing a diary, 87 (51%) reported at least one bleeding event and 36 (21%) had a supratherapeutic INR. Seventy-three patients (43%) indicated they had used at least one CAM product previously reported to interact with warfarin. Warfarin use of less than 3 months' duration was the only statistically significant risk factor identified for supratherapeutic INR. The CAM therapies associated with an increased risk of self-reported bleeding included cayenne, ginger, willow bark, St. John's wort, and coenzyme Q(10). Use of more than one CAM while receiving warfarin was also a significant risk factor. Two CAMs were independently associated with an increased risk of self-reported bleeding: coenzyme Q(10) (odds ratio [OR] 3.69, 95% confidence interval [CI] 1.88-7.24) and ginger (OR 3.20, 95% CI 2.42-4.24). Other risk factors significantly associated with increased bleeding included high target INR (2.5-3.5), diarrhea, acetaminophen use, increased alcohol consumption, and increased age.


CONCLUSIONS
The use of CAM by patients receiving warfarin is common, and consumption of coenzyme Q(10) or ginger appears to increase the risk of bleeding in this population.
Shalansky
Stephen
S
Pharmacy Department, Vancouver Coastal Health-Providence Health Care Pharmacy Services, Vancouver, British Columbia, Canada.
Lynd
Larry
L
Richardson
Kathryn
K
Ingaszewski
Andrew
A
Kerr
Charles
C
D000082:Acetaminophen / Q000009:adverse effects; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D002170:Canada; D003067:Coenzymes / Q000009:adverse effects; D000529:Complementary Therapies / Q000009:adverse effects*; D003967:Diarrhea / Q000150:complications; D019587:Dietary Supplements / Q000009:adverse effects; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D020939:Zingiber officinale / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced*; D041743:Herb-Drug Interactions; D006801:Humans; D019934:International Normalized Ratio; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy / Q000009:adverse effects; D010946:Plants, Medicinal / Q000009:adverse effects; D011446:Prospective Studies; D012307:Risk Factors; D014451:Ubiquinone / Q000009:adverse effects / Q000031:analogs & derivatives; D014815:Vitamins / Q000009:adverse effects; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
D000925:Anticoagulants; D003067:Coenzymes; D014815:Vitamins; D014451:Ubiquinone; D000082:Acetaminophen; D000431:Ethanol; D014859:Warfarin; C024989:coenzyme Q10