Frontiers in Pharmacology: New evidence from a meta-analysis of phthalophenyl in the treatment of stroke

In September 2022, the research results of Professor Wang Deren's team at West China Hospital, "DL-3-n-butylphthalide for acute ischemic stroke: An updated systematic review and meta-analysis of randomized controlled trials" in Frontiers in Pharmacology (IF= 5.

Butylphthalein is a class I chemical new drug developed and produced in China, and basic research suggests that it can improve local circulation, reduce infarction area, reduce brain tissue damage and restore nerve function

The objective of this study was to update the published systematic review by adding newly published clinical trials (between October 2009 and October 2019) and to further refine the research methodology to evaluate the efficacy and safety

Research Methods

1.

Randomized controlled trial reports published in Chinese and English should be included and the following two criteria must be met: (1) Clearly describe the randomization method used in the trial; (2) The sample size of a single test > 100

2.

Patients with acute ischemic stroke (within 14 days of onset) are of no particular

3.

(1) Buprophthalein was compared with placebo (the other treatments in the two groups were consistent); (2) Butylphthalide combined with other treatments and other treatments alone

4.

Trials using one or more of the following efficacy indicators may be included

Results of the study

1.
Include the baseline features of the trial

A total of 7,431 articles related to butylphthalein were detected, and after excluding studies that did not meet the inclusion criteria, a total of 57 studies involving 8,747 patients
were included.

Of the 57 studies, 20 trials were treated with buc-phthalein softgels, 29 were butylphthalide injections, and the remaining 8 were treated with buc-phthalein sequential therapy
.

Figure 1 Study inclusion flowchart

2.
Compound outcomes of death and disability

Fixed-effect meta-analyses showed that butylphthalide reduced the composite outcome
of death and disability.

The combined outcome incidence of death and disability was 25.
38% (33/130) in the butylphthalein group and 43.
08% (56/130)
in the control group.

(RR 0.
59, 95% CI 0.
42 to 0.
83; patient=260; study=2; I²=10%)
.
)

Figure 2 Meta-analysis of the composite outcomes of death and disability at 3 months of follow-up

3.
Death

Fixed-effect meta-analysis showed that butylphthalide was significantly associated
with a reduction in deaths during treatment or follow-up.

Deaths during treatment or follow-up were reported in 10 trials, with mortality from 0.
51% in the butylphthalein group (6/1,184) and 1.
81% (20/1,103) in the control group (RR 0.
32, 95% CI 0.
13 to 0.
75; patient = 2,287; study = 10; I²=0%)
.

Figure 3 Meta-analysis of death during treatment or follow-up

4.
Disability

In terms of mRS scores, fixed-effect meta-analyses of four trials showed a significant reduction in mRS scores in the butylphthalein group (MD-0.
80, 95% CI -0.
88 to -0.
72; patients=568; studies=4; I²=0%)
.

Figure 4 Meta-analysis of mRS score after treatment as an indicator of functional independence

In terms of Barthel index (BI), 22 trials involving 2,975 patients and random-effects meta-analysis showed a significant increase in the Barthel index in the butylphthalein group (MD 11.
08, 95% CI 9.
10 to 13.
05; patient=2,968; study=22; I2=91%)
.

Figure 5 Meta-analysis of the Barthel index at the end of treatment or follow-up as an indicator of basic activity ability of daily living

5.
Improvement of neurological deficits

Random-effects meta-analysis of 48 trials using NIHSS to assess neurofunctional deficits, but two of the trials did not report specific NIHSS scores, showed a significant decrease in NIHSS scores in patients in the butylphthalein group (MD -3.
39, 95% CI -3.
76 to -3.
03; patient = 7,283; study = 46; I²=85%)
.

Four trials (543 patients) assessed neurological deficits using CSS scores, and random-effects meta-analysis showed that buccinylphthalein therapy significantly reduced CSS scores (MD -4.
16, 95% CI -7.
60 to -0.
73; patient=543; study=4; I²=91%)
.

Two trials used a rehabilitation regimen and evaluation standard scale for cerebrovascular disease or the modified Edinburgh-Scandinavian Neurological Deficit Score Scale (MESSS) to assess neurological deficits, respectively, and one trial used an unknown scale, and a meta-analysis of three trials showed that the buccinthalide group was associated with significant improvement in neurofunction compared with controls (MD -3.
73, 95% CI -4.
64 to -2.
82; patient=345; study=3;I).
²=0%）
。

Figure 6 Meta-analysis of NIHSS scores at the end of treatment or follow-up as an indicator of neurological deficits

Conclusion of the study

Reference: Wang H, Ye K, Li D, Liu Y, Wang D.
DL-3-n-butylphthalide for acute ischemic stroke: An updated systematic review and meta-analysis of randomized controlled trials.
Front Pharmacol.
2022 Sep 2; 13:963118.
doi: 10.
3389/fphar.
2022.
963118.
PMID: 36120291; PMCID: PMC9479342.