Does Ginkgo biloba special extract EGb 761 provide additional effects on coagulation and bleeding when added to acetylsalicylic acid 500 mg daily?
OBJECTIVE
The aim of this study was to determine whether Ginkgo biloba special extract EGb 761 amplifies the known effects of acetylsalicylic acid (ASA) on platelet aggregation, bleeding time or other coagulation parameters in healthy subjects.


METHODS
In a double-blind, double-dummy procedure, 50 healthy male subjects (20-44 years) were randomly allocated in equal numbers to one of two possible treatment sequences, i.e. ASA followed by ASA + EGb 761 or ASA + EGb 761 followed by ASA. Each treatment lasted 7 days; the washout period between treatments was 3 weeks. Study medication was taken twice daily (ASA group: ASA 500 mg tablet + placebo-coated tablet in the morning and placebo tablet + placebo-coated tablet in the evening; ASA + EGb 761 group: ASA 500 mg tablet + EGb 761 120 mg-coated tablet in the morning and placebo tablet + EGb 761 120 mg-coated tablet in the evening), resulting in a daily dose of ASA 500 mg in the ASA group and 500 mg ASA + 240 mg EGb 761 in the ASA + EGb 761 group. Bleeding time, coagulation parameters and platelet activity in response to various agonists were determined. In addition, adverse events, laboratory variables and vital signs were measured. The primary variable bleeding time was assessed in confirmatory analysis, all other variables were evaluated descriptively. The coagulation variables were analysed by ANOVA under the crossover model.


RESULTS
ASA given alone clearly prolonged bleeding time. ASA and the combination of ASA + EGb 761 exerted quite similar effects on all coagulation parameters measured, including bleeding time (ASA alone: 4.1 min before therapy, 6.2 min after therapy; ASA + EGb 761: 4.2 min before therapy, 6.3 min after therapy; ratio of means: 1.01, 90% CI 0.86, 1.19) and agonist-induced platelet aggregation (collagen-induced platelet aggregation - ASA: 84.5% before therapy, 81.0% after therapy; ASA + EGb 761: 86.6% before therapy, 81.0% after therapy; ratio of means: 1.00, 90% CI 0.95, 1.05; adenosine diphosphate-induced platelet aggregation - ASA: 72.6% before therapy, 47.2% after therapy; ASA + EGb 761: 71.7% before therapy, 44.8% after therapy; ratio of means: 0.95, 90% CI 0.85, 1.06). Both treatments were well tolerated, and both the number and nature of adverse events in the two groups were similar.


CONCLUSIONS
Our findings suggest that co-administration of ASA and EGb 761 does not constitute a safety risk, including in an elderly patient population undergoing treatment with EGb 761.
Wolf
Hellmut R D
HR
Innere Medizin, Diakonie Krankenhaus, Bad Kreuznach, Germany. hellmut-wolf@t-online.de
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D020441:Ginkgo biloba; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D000096983:Ginkgo Extract
D001241:Aspirin; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract