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Meta-Analysis
. 2019 Feb 13;2(2):CD001928.
doi: 10.1002/14651858.CD001928.pub3.

Calcium antagonists for acute ischemic stroke

Jing Zhang  1 , Jia Liu, Dan Li, Canfei Zhang, Ming Liu
Affiliations
Meta-Analysis

Calcium antagonists for acute ischemic stroke

Jing Zhang et al. Cochrane Database Syst Rev. .

Abstract

Background: The sudden loss of blood supply in ischemic stroke is associated with an increase of calcium ions within neurons. Inhibiting this increase could protect neurons and might reduce neurological impairment, disability, and handicap after stroke.

Objectives: To assess the effects of calcium antagonists for reducing the risk of death or dependency after acute ischemic stroke. We investigated the influence of different drugs, dosages, routes of administration, time intervals after stroke, and trial design on the outcomes.

Search methods: The evidence is current to 6 February 2018. We searched the Cochrane Stroke Group Trials Register (6 February 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), MEDLINE Ovid (1950 to 6 February 2018), Embase Ovid (1980 to 6 February 2018), and four Chinese databases (6 February 2018): Chinese Biological Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI), Chinese Scientific Periodical Database of VIP information, and Wanfang Data. We also searched the following trials registers: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN registry, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Registry, and we contacted trialists and researchers.

Selection criteria: Randomized controlled trials comparing a calcium antagonist versus control in people with acute ischemic stroke.

Data collection and analysis: Two review authors independently selected trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the quality of the evidence. We used death or dependency at the end of long-term follow-up (at least three months) in activities of daily living as the primary outcome. We used standard Cochrane methodological procedures.

Main results: We included 34 trials involving 7731 participants. All the participants were in the acute stage of ischemic stroke, and their age ranged from 18 to 85 years, with the average age ranging from 52.3 to 74.6 years across different trials. There were more men than women in most trials. Twenty-six trials tested nimodipine, and three trials assessed flunarizine. One trial each used isradipine, nicardipine, PY108-608, fasudil, and lifarizine. More than half of these trials followed participants for at least three months. Calcium antagonists showed no effects on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.98 to 1.13; 22 trials; 22 studies; 6684 participants; moderate-quality evidence) or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to 1.17; 31 trials; 7483 participants; moderate-quality evidence). Thirteen trials reported adverse events, finding no significant differences between groups. Most trials did not report the allocation process or how they managed missing data, so we considered these at high risk of selection and attrition bias. Most trials reported double-blind methods but did not state who was blinded, and none of the trial protocols were available.

Authors' conclusions: We found no evidence to support the use of calcium antagonists in people with acute ischemic stroke.

PubMed Disclaimer

Conflict of interest statement

Jing Zhang: none known. Jia Liu: none known. Dan Li: none known. Canfei Zhang: none known. Ming Liu: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: primary outcome at end of follow‐up.
5
5
Funnel plot of comparison: death at end of treatment period.
6
6
Funnel plot of comparison: death at end of follow‐up.
7
7
Funnel plot of comparison: adverse events (all) during treatment period.
1.1
1.1. Analysis
Comparison 1 Calcium antagonists versus control in acute ischemic stroke, Outcome 1 Death or dependency at end of follow‐up.
1.2
1.2. Analysis
Comparison 1 Calcium antagonists versus control in acute ischemic stroke, Outcome 2 Death at end of treatment period.
1.3
1.3. Analysis
Comparison 1 Calcium antagonists versus control in acute ischemic stroke, Outcome 3 Death at end of follow‐up.
1.4
1.4. Analysis
Comparison 1 Calcium antagonists versus control in acute ischemic stroke, Outcome 4 Recurrence of stroke at end of follow‐up.
1.5
1.5. Analysis
Comparison 1 Calcium antagonists versus control in acute ischemic stroke, Outcome 5 Any adverse event during treatment period.
1.6
1.6. Analysis
Comparison 1 Calcium antagonists versus control in acute ischemic stroke, Outcome 6 Hypotension during treatment period (reason to stop treatment).
1.7
1.7. Analysis
Comparison 1 Calcium antagonists versus control in acute ischemic stroke, Outcome 7 Mean systolic blood pressure during or at end of treatment.
2.1
2.1. Analysis
Comparison 2 Calcium antagonists versus control: subgroup analysis, Outcome 1 Death or dependency at end of follow‐up by route of administration.
2.2
2.2. Analysis
Comparison 2 Calcium antagonists versus control: subgroup analysis, Outcome 2 Death or dependency at end of follow‐up by dose: indirect comparisons.
2.3
2.3. Analysis
Comparison 2 Calcium antagonists versus control: subgroup analysis, Outcome 3 Death or dependency at end of follow‐up by dose: direct comparisons.
2.4
2.4. Analysis
Comparison 2 Calcium antagonists versus control: subgroup analysis, Outcome 4 Death or dependency at end of follow‐up by time of start of treatment.
3.1
3.1. Analysis
Comparison 3 Calcium antagonists versus control: sensitivity analysis, Outcome 1 Death or dependency at end of follow‐up in multicenter placebo controlled trials.
3.2
3.2. Analysis
Comparison 3 Calcium antagonists versus control: sensitivity analysis, Outcome 2 Publication status.
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Update of

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