Calcium antagonists for acute ischemic stroke

Question

Are calcium antagonist drugs beneficial for people who have had an acute ischemic stroke?

Background
Most strokes are due to reduced blood flow with obstruction of large and small arteries. As a result, calcium ions flood into the brain cells and contribute to brain cell death. Calcium antagonists may reduce the damage by preventing the influx of calcium ions. In the past 20 years, there have been many clinical trials focusing on various calcium antagonists for acute ischemic stroke. We reviewed the evidence about the effects of these medicines compared with placebo or control in people with acute ischemic stroke.

Study characteristics
We identified 34 studies to February 6, 2018 that met our inclusion criteria; they involved 7731 participants and investigated different kinds of drugs. Twenty-six trials tested nimodipine, and three trials assessed flunarizine. One trial each used isradipine, nicardipine, PY108-608, fasudil, and lifarizine.

Key results
There was no difference in deaths or dependency between participants who received calcium antagonists or not.

Quality of the evidence
There is no evidence that calcium antagonists after acute ischemic stroke could save lives or reduce disability. The evidence was moderately reliable, which means that further research is unlikely to change our conclusions.

Authors' conclusions: 

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

Read the full 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 strategy: 

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.

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