PURPOSE: To evaluate the safety of certain thrombolytic agents which can currently be a treatment option for acute ischemic stroke.METHODS: Studies were identified using MEDLINE (1966 to January 2002), the Cochrane Controlled Trial Register, and references of the papers selected. A number of biomedical and stroke related websites were also searched. Randomized-placebo-controlled trials of thrombolytic agents for the treatment of acute ischemic stroke patients were eligible. Streptokinase (SK) trials were excluded since all major SK trials were terminated early and a meta-analysis of individual patient data did not indicate a subgroup of patients for whom SK can be beneficial. Study quality was evaluated by using a previously validated scale. Data was extracted in duplicate by two independent investigators. Symptomatic intracranial hemorrhage (SIH) within the first ten days and mortality from all causes during follow-up were the outcomes. Odds ratio, absolute risk difference, and number needed to harm (NNH) which is the number of patients need to be treated to cause one additional adverse outcome were calculated to evaluate the safety of thrombolytic agents. According to homogeneity test results, a fixed effects model for SIH and a random-effects model for mortality were used to pool the individual effects of trials.RESULTS: 11 randomized controlled trials involving 3,643 patients were included in the analysis. Thrombolytic therapy was associated with a three-fold increase (odds ratio [OR], 3.4; 95% confidence interval [CI], 2.4-4.75; p < 0.0001) in symptomatic intracranial hemorrhage (SIH) and an insignificant increase (OR, 1.07; 95% CI, 0.83-1.39; p = 0.291) in mortality. The treatment was associated with an absolute risk increase of 58 per 1000 persons (95% CI, 43-72; p < 0.0001) for SIH and 11 per 1000 persons (95% CI, (-24)-48; p = 0.261) for mortality. NNH was 17 (95% CI, 13-22) for SIH, and 84 (95% CI, including 0) for mortality. When including only trials using rt-PA, treatment was associated with a significant increase (OR, 3.6; 95% CI, 2.5-5.2; p < 0.0001) in symptomatic SIH and an insignificant increase (OR, 1.25; 95% CI, 0.87-1.78; p = 0.119) in mortality.CONCLUSION: These findings suggest that thrombolytic therapy increases the risk of symptomatic hemorrhage in 10 days when compared with placebo, however there is no significant difference in mortality during follow-up between the groups.
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机译：目的：评估某些溶栓剂的安全性，这些溶栓剂目前可作为急性缺血性卒中的治疗选择。方法：使用MEDLINE（1966年至2002年1月），Cochrane对照试验注册簿和所选论文的参考文献进行了研究鉴定。还搜索了许多生物医学和中风相关的网站。溶栓剂治疗急性缺血性中风患者的随机安慰剂对照试验是合格的。链激酶（SK）试验被排除在外，因为所有主要的SK试验均已提前终止，并且对单个患者数据的荟萃分析未显示SK可能有益的亚组患者。研究质量通过使用先前验证的量表进行评估。数据是由两名独立调查员一式两份提取的。结果是头十天内出现症状性颅内出血（SIH），并且随访期间所有原因导致的死亡率。计算赔率，绝对风险差异和所需伤害数（NNH），即需要治疗以引起另一种不良后果的患者数，以评估溶栓剂的安全性。根据同质性测试结果，使用SIH固定效应模型和死亡率随机效应模型来汇总试验的个体效应。结果：11项随机对照试验涉及3,643例患者，被纳入分析。溶栓治疗与有症状的颅内出血（SIH）增加三倍（比值比[OR]为3.4; 95％置信区间[CI]为2.4-4.75; p <0.0001），且无明显增加（OR为1.07） ; 95％CI，0.83-1.39; p = 0.291）。该治疗与SIH的绝对风险增加（58/1000人（95％CI，43-72; p <0.0001））和每1000人11的绝对风险增加（95％CI，（-24）-48; p = 0.261）死亡率。 SIH的NNH为17（95％CI，13-22），死亡率为84（95％CI，包括0）。当仅包括使用rt-PA的试验时，治疗与有症状的SIH显着增加（OR，3.6; 95％CI，2.5-5.2; p <0.0001）和显着增加（OR，1.25; 95％CI，0.87）相关结论：这些发现表明，与安慰剂相比，溶栓治疗在10天之内增加了发生症状性出血的风险，但是两组之间在死亡率方面无显着差异。
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