Muir K W, Roberts M
Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland.
Drugs Aging. 2000 Jan;16(1):41-54. doi: 10.2165/00002512-200016010-00004.
Clinical trials in the 1990s of intravenous thrombolysis for ischaemic stroke have involved over 3000 patients. Alteplase given within 3 hours of onset significantly reduces the combined end-point of death and disability. Although alteplase appears safe when given up to 6 hours after onset, individual trials have failed to confirm efficacy beyond 3 hours. Meta-analysis indicates that intravenous alteplase given up to 6 hours after stroke onset significantly reduces death or dependence 3 months after stroke. Two trials of intra-arterial pro-urokinase confirm benefits of treatment up to 6 hours in highly selected patients with angiographically confirmed proximal middle cerebral occlusion. Streptokinase increased the risk of early death significantly in 3 trials, with no overall reduction in eventual death and disability. Patients over 80 years have been excluded from most trials of alteplase, and experience in this age group is minimal. Increased incidence and poorer functional outcome in the elderly mean that thrombolysis may have greater absolute benefit in this group than in the young, but there is also a higher prevalence of absolute or relative potential contraindications to treatment (ranging from increased use of anticoagulant drugs to higher prevalence of atrial fibrillation). Further trials are necessary to address age restrictions and other important issues in the use of alteplase. Thrombolysis is likely to remain feasible for a minority of stroke patients of all ages, and there is a need for other acute treatment options.
20世纪90年代针对缺血性中风进行的静脉溶栓临床试验涉及3000多名患者。在发病3小时内给予阿替普酶可显著降低死亡和残疾的综合终点。尽管在发病后6小时内给予阿替普酶似乎是安全的,但个别试验未能证实3小时后仍有疗效。荟萃分析表明,在中风发作后6小时内给予静脉阿替普酶可显著降低中风后3个月的死亡或依赖风险。两项动脉内使用尿激酶原的试验证实,对于经血管造影证实为大脑中动脉近端闭塞的高度选择患者,在6小时内进行治疗有益。在3项试验中,链激酶显著增加了早期死亡风险,最终死亡和残疾并未总体减少。大多数阿替普酶试验都排除了80岁以上的患者,该年龄组的经验极少。老年人发病率增加且功能预后较差,这意味着溶栓在该组中可能比年轻人有更大的绝对益处,但治疗的绝对或相对潜在禁忌证的患病率也更高(从抗凝药物使用增加到房颤患病率更高)。有必要进行进一步试验以解决年龄限制和使用阿替普酶的其他重要问题。溶栓可能对所有年龄段的少数中风患者仍然可行,并且需要其他急性治疗选择。