Chan ALF, Leung HWC, Wu J-W, Chien T-W. Risk of hemorrhage associated with co-prescriptions for Ginkgo biloba and antiplatelet or anticoagulant drugs. J Altern Complement Med. June 2011;17(6):513-517.
Ginkgo (Ginkgo biloba) extract (GBE), widely used in traditional medicine, has been shown to improve memory and mental faculties affected by aging and senility, dementia, and peripheral vascular and neurosensory diseases. Preclinical research has found that GBE and ginkgolides B and C inhibit platelet aggregation. In addition, several reviews suggest that ginkgo may increase the risk of bleeding, but randomized clinical trials show that GBE is not correlated with the inhibition of coagulation or platelet aggregation. To investigate whether GBE use, either alone or in combination with antiplatelet or anticoagulant medication, is associated with an increased risk of hemorrhage, this analysis examined data from a population-based health care dataset.
Analyzed data were used from approximately 200,000 patients from January 1, 2000 to December 31, 2008 in the Longitudinal Health Insurance Database of Taiwan (LHID), maintained by the National Health Research Institute. The LHID contains a random sample of ambulatory patients with comparable age, sex, and prescription distributions from the 2,500,000 enrollees in National Health Insurance. Any brand of GBE prescribed at the same time as any of the antiplatelet drugs clopidogrel, cilostazol, or ticlopidine or the anticoagulant warfarin was considered a combination. Included as newly diagnosed hemorrhage were those occurring within 14 days of GBE prescription, and the frequency and prevalence of GBE and combination prescriptions were analyzed. Patients were excluded if hemorrhage was diagnosed before the first GBE prescription or if hemorrhage was determined to be caused by subdural hematoma, postoperative bleeding, trauma, or accident.
In general, total prescriptions increased from 1,916,652 in 2000 to 2,023,164 in 2008 with an increase in ginkgo prescriptions across all sampled age groups; a notable increase in ginkgo prescriptions in patients over 60 years old was observed (0.51% in 2000 to 0.7% in 2008). The analyses revealed that the co-prescription of GBE with either clopidogrel, cilostazol, ticlopidine, or warfarin was not significantly associated with a risk of hemorrhage (odds ratio [OR]: 2.0, 95% confidence interval [CI]: 0.6-6.5, P=0.479); however, in patients taking GBE by itself (n=7640) or as a co-prescription (n=60), a significant risk was observed in those older than 65 years (OR: 3.86, 95% CI: 2.8-5.3, P<0.0001) and in men (OR: 1.5, 95% CI: 1.1-2.0, P=0.0157). These results were approximately the same between both univariate and multivariate analyses controlled for age, gender, and co-prescriptions.
An increase in the prescription of ginkgo was observed, perhaps due to the use of this herb to boost circulation or parallel with an increase of herbal supplement use worldwide. Although the risk of hemorrhage from use of ginkgo with antiplatelet and anticoagulant medication was not significant overall, it was significant in elderly and male patients taking ginkgo. Thus, according to the authors, these data especially support caution with the use of GBE in older patients and those with known bleeding risks.
This study is notable for analyzing the risk of GBE in combination with clopidogrel, cilostazol, ticlopidine, and warfarin in a large population sample. Limitations include a lack of description of GBE. The data accessed do not include information on laboratory data, GBE product or dosage variation, or over-the-counter use of GBE or aspirin. Despite these problems, this analysis provides critical information about potential herb-drug interactions involving ginkgo use in combination with other drugs and of risks associated with ginkgo use itself.—Amy C. Keller, PhD