Incidence of neutropenia in patients with ticlopidine/Ginkgo biloba extract combination drug for vascular events: A post-marketing cohort study

Han Gil Jeong, Jae Sun Yoon, Juneyoung Lee, Hee Joon Bae

Research output: Contribution to journalArticle

Abstract

Background and purpose The ticlopidine/Ginkgo biloba ext. combination drug (Yuclid) is used as an antiplatelet agent for prevention of vascular events since its approval in 2008. The purpose of this study is to explore the safety of ticlopidine/Ginkgo biloba combination, mainly regarding the incidence of neutropenia, through a post-marketing surveillance study. Methods From March 2009 to October 2015, a total of 4839 subjects had been enrolled in this study. The enrollments were conducted by 152 doctors of 89 hospitals according to the regulations for post-marketing surveillance programs in Korea. If a subject was administered the drug once, he/she was included in the safety analysis set for any adverse events and bleedings, and the primary safety evaluation regarding neutropenia was conducted in subjects who completed 3-month blood test follow-up. We predefined that 1% reduction in neutropenia incidence by ticlopidine/Ginkgo biloba ext. combination from the previously reported incidence of ticlopidine of 2.3% was clinically meaningful. Results Among the safety analysis set of 4831 patients (99.8% of the enrolled subjects), 3150 (65.1%) completed evaluation for neutropenia at 3 months which is the primary safety endpoint. The major causes of dropout were no follow-up visit at 3 months (n = 1016) and violation of the follow-up period (n = 503). Nine patients experienced neutropenia (Absolute neutrophil count [ANC] 1200mm3) and the estimated cumulative incidence at 3 months is 0.29% (95% confidence interval, 0.13%– 0.54%). Severe neutropenia (ANC 450mm3) did not occur in any patients. Conclusions The incidence of neutropenia with addition of Ginkgo biloba ext. to ticlopidine may be lower than the previously reported incidence of neutropenia with ticlopidine, which needs to be confirmed in randomized controlled trials.

Original languageEnglish
Article numbere0217723
JournalPloS one
Volume14
Issue number6
DOIs
Publication statusPublished - 2019 Jun 1

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Ticlopidine
Ginkgo biloba
combination drug therapy
neutropenia
Drug Combinations
Marketing
Neutropenia
cohort studies
blood vessels
Blood Vessels
marketing
Cohort Studies
incidence
Incidence
extracts
Safety
safety assessment
neutrophils
Neutrophils
Platelet Aggregation Inhibitors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Incidence of neutropenia in patients with ticlopidine/Ginkgo biloba extract combination drug for vascular events : A post-marketing cohort study. / Jeong, Han Gil; Yoon, Jae Sun; Lee, Juneyoung; Bae, Hee Joon.

In: PloS one, Vol. 14, No. 6, e0217723, 01.06.2019.

Research output: Contribution to journalArticle

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abstract = "Background and purpose The ticlopidine/Ginkgo biloba ext. combination drug (Yuclid) is used as an antiplatelet agent for prevention of vascular events since its approval in 2008. The purpose of this study is to explore the safety of ticlopidine/Ginkgo biloba combination, mainly regarding the incidence of neutropenia, through a post-marketing surveillance study. Methods From March 2009 to October 2015, a total of 4839 subjects had been enrolled in this study. The enrollments were conducted by 152 doctors of 89 hospitals according to the regulations for post-marketing surveillance programs in Korea. If a subject was administered the drug once, he/she was included in the safety analysis set for any adverse events and bleedings, and the primary safety evaluation regarding neutropenia was conducted in subjects who completed 3-month blood test follow-up. We predefined that 1{\%} reduction in neutropenia incidence by ticlopidine/Ginkgo biloba ext. combination from the previously reported incidence of ticlopidine of 2.3{\%} was clinically meaningful. Results Among the safety analysis set of 4831 patients (99.8{\%} of the enrolled subjects), 3150 (65.1{\%}) completed evaluation for neutropenia at 3 months which is the primary safety endpoint. The major causes of dropout were no follow-up visit at 3 months (n = 1016) and violation of the follow-up period (n = 503). Nine patients experienced neutropenia (Absolute neutrophil count [ANC] 1200mm3) and the estimated cumulative incidence at 3 months is 0.29{\%} (95{\%} confidence interval, 0.13{\%}– 0.54{\%}). Severe neutropenia (ANC 450mm3) did not occur in any patients. Conclusions The incidence of neutropenia with addition of Ginkgo biloba ext. to ticlopidine may be lower than the previously reported incidence of neutropenia with ticlopidine, which needs to be confirmed in randomized controlled trials.",
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