Zhang Jing, Liu Jia, Li Dan, Zhang Canfei, Liu Ming
Department of Neurology, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Beijing, Beijing, China, 100053.
Cochrane Database Syst Rev. 2019 Feb 13;2(2):CD001928. doi: 10.1002/14651858.CD001928.pub3.
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.
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.
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.
Randomized controlled trials comparing a calcium antagonist versus control in people with acute ischemic stroke.
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.
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.
缺血性卒中时突然的血液供应中断与神经元内钙离子增加有关。抑制这种增加可保护神经元，并可能减轻卒中后的神经功能缺损、残疾和残障。
评估钙拮抗剂对降低急性缺血性卒中后死亡或依赖风险的作用。我们研究了不同药物、剂量、给药途径、卒中后时间间隔及试验设计对结果的影响。
证据截至2018年2月6日。我们检索了Cochrane卒中小组试验注册库（2018年2月6日）、Cochrane对照试验中央注册库（CENTRAL；2018年第2期）、MEDLINE Ovid（1950年至2018年2月6日）、Embase Ovid（1980年至2018年2月6日）以及四个中文数据库（2018年2月6日）：中国生物医学文献数据库（CBM-disc）、中国知网（CNKI）、维普中文科技期刊数据库和万方数据。我们还检索了以下试验注册库：ClinicalTrials.gov、欧盟临床试验注册库、卒中试验注册库、ISRCTN注册库、世界卫生组织国际临床试验注册平台和中国临床试验注册中心，并联系了试验者和研究者。
比较钙拮抗剂与对照组治疗急性缺血性卒中患者的随机对照试验。
两名综述作者独立选择试验、提取数据、评估偏倚风险，并采用GRADE方法评估证据质量。我们将长期随访（至少三个月）结束时日常生活活动中的死亡或依赖作为主要结局。我们采用标准的Cochrane方法学程序。
我们纳入了34项试验，涉及7731名参与者。所有参与者均处于缺血性卒中急性期，年龄在18至85岁之间，不同试验的平均年龄在52.3至74.6岁之间。大多数试验中男性多于女性。26项试验使用尼莫地平，3项试验评估氟桂利嗪。各有1项试验使用伊拉地平、尼卡地平、PY108 - 608、法舒地尔和利法利嗪。这些试验中超过一半对参与者随访至少三个月。钙拮抗剂对主要结局（风险比（RR）1.05；95%置信区间（CI）0.98至1.13；22项试验；22项研究；6684名参与者；中等质量证据）或随访结束时的死亡（RR 1.07，95%CI 0.98至1.17；31项试验；7483名参与者；中等质量证据）均无影响。13项试验报告了不良事件，未发现组间有显著差异。大多数试验未报告分配过程或处理缺失数据的方法，因此我们认为这些试验存在较高的选择和失访偏倚风险。大多数试验报告了双盲方法，但未说明谁被设盲，且均未提供试验方案。
我们没有发现证据支持在急性缺血性卒中患者中使用钙拮抗剂。
