Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial

Abstract

Purpose: To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) in acute ischaemic stroke and its impact on the recurrence of vascular events.

Methods: We conducted a multicentre, prospective, randomised, open label, blinded, controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province. Participants were assigned to the GBE group (450 mg GBE with 100 mg aspirin daily) or the control group (100 mg aspirin daily) for 6 months. The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months. Secondary outcomes were other neuropsychological tests of cognitive and neurological function, the the incidence of adverse events and vascular events.

Results: 348 patients were enrolled: 179 in the GBE group and 169 in the control group. With 18 patients lost to follow-up, the dropout rate was 5.17%. Admission data between two groups were similar, but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores (-2.77±0.21 vs -1.99±0.23, P=0.0116 (30 days); -3.34±0.24 vs -2.48±0.26, P=0.0165 (90 days); -4.00±0.26 vs -2.71±0.26, P=0.0004 (180 days)) compared with controls. The National Institutes of Health Stroke Scale scores at 12 and 30 days, the modified Rankin Scale scores for independent rate at 30, 90 and 180 days, and the Barthel Index scores at 30, 90 and 180 days in the GBE group were significantly improved compared with controls. Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30, 90 and 180 days, Webster's digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days. No significant differences were seen in the incidence of adverse events or vascular events.

Conclusions: We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events.

Trial registration number: ChiCTR-TRC-12002688.

Keywords: cognitive function; ginkgo biloba extract; incidence of vascular events; ischemic stroke; neurological function.

Figure 1

Flowchart illustrating the trial design. BI, Barthel index; EDI, Executive Dysfunction Index; FAS, full analysis set; GBE, Ginkgo biloba extract; MMSE, Mini-Metal State Examination; MOCA, Montreal Cognitive Assessment; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; WDT, Webster’s digit symbol test.

Figure 2

Montreal Cognitive Assessment (MoCA) scores were evaluated as a measure of post stroke cognitive function in each participant during the study period. (A) MoCA scores after acute stroke in the Ginkgo biloba extract (GBE) group and in the control group at admission, and at 12, 30, 90 and 180 days. (B) Decline in MoCA scores (deMoCA) after acute stroke in the GBE and control groups at 12, 30, 90 and 180 days. deMoCA, MoCA score at admission−MoCA score at the indicated time points. *P<0.05 versus control group.

Figure 3

National Institutes of Health Stroke Scale (NIHSS) scores were evaluated as a measure of neurological deficit in patients within 30 days, and the Barthel index (BI) scores were defined as activities of daily living within 180 days of acute stoke onset. (A) NIHSS scores at admission, and at 12 and 30 days after acute stroke in the Ginkgo biloba extract (GBE) group and the control group. (B) Decline in NIHSS scores (deNIHSS) after acute stroke in the GBE and control groups at 12 and 30 days. (C) BI scores after acute stroke in the GBE and control groups at admission, and at 12, 30, 90 and 180 days.(D) Decline in BI scores (deBI) at 12, 30, 90 and 180 days. deNIHSS, NIHSS score at admission–NIHSS score at the indicated time points. deBI, BI score at admission–BI score at the indicated time points. *P<0.05, **P<0.01 versus control group.

Figure 4

Modified Rankin Scale (mRS) scores were evaluated as a measure of neurological outcome function of participants from 30 to 180 days after stoke. (A) Independent mRS rate after acute stroke in the Ginkgo biloba extract (GBE) group and the control group at 30, 90 and 180 days. (B) Distribution of mRS scores after acute stroke in the GBE and control groups at 30, 90 and 180 days. Independent mRS rate was defined as an mRS score of ≤2. **P<0.01 versus control group.

Figure 5

Mini-Metal State Examination (MMSE) scores, Executive Dysfunction Index (EDI) scores and Webster’s digit symbol test (WDT) scores were evaluated as a measure of post stroke cognitive executive function in patients at each time point. (A, C, E) MMSE, EDI and WDT scores after acute stroke in the Ginkgo biloba extract (GBE) group and in the control group at admission, and at 12, 30, 90 and 180 days. (B, D, F) Decline in MMSE scores (deMMSE), EDI scores (deEDI) and WDT scores (deWDT) at 12, 30, 90 and 180 days. deMMSE, MMSE score at admission–MMSE score at the indicated time points; deEDI, EDI score at admission–EDI score at the indicated time points; deWDT, WDT score at admission–WDT score at the indicated time points. *P<0.05 versus control group.