Battershill P E, Benfield P, Goa K L
Adis International Limited, Auckland, New Zealand.
Drugs Aging. 1994 Jan;4(1):63-86. doi: 10.2165/00002512-199404010-00007.
Streptokinase has been administered to many thousands of elderly patients with acute myocardial infarction. Results of large, randomised trials provide convincing evidence that intravenous streptokinase confers a distinct survival benefit in this population subgroup following myocardial infarction. The placebo-controlled ISIS-2 study demonstrated a 5-week absolute mortality reduction of 38 per 1000 patients aged 60 to 69 years administered streptokinase, compared with only 16 per 1000 for patients aged less than 60 years. Combining streptokinase with aspirin further reduces mortality, as shown by a 5-week absolute mortality reduction of 70 per 1000 patients aged 60 to 69 years administered this regimen in the ISIS-2 trial. While ideally patients should receive streptokinase as soon as possible after symptom onset, late benefit has been observed in patients presenting up to 12 hours after pain onset, as is often the case with the elderly. Indeed, in patients treated > 6 hours after infarct in the GUSTO trial, streptokinase produced lower mortality results than accelerated recombinant tissue plasminogen activator (rt-PA). However, in contrast to the similar effects of streptokinase and conventionally administered rt-PA on overall survival demonstrated in previous large trials, the GUSTO study showed a lower mortality rate for accelerated rt-PA than for streptokinase in the elderly and in the total patient population. The most frequent adverse effects associated with streptokinase therapy are haemorrhagic complications, with an incidence of 0.4% for major bleeding (requiring transfusion) and 3.6% for minor bleeding among the total population in the GISSI-1 and ISIS-2 trials. An excess of stroke, particularly haemorrhagic stroke, occurring with rt-PA in GUSTO and other major mortality trials affirms the use of streptokinase as a suitable option in the elderly who are at increased risk of this complication. Significantly reduced values of end-systolic volume and regional wall motion index have been observed in elderly patients following streptokinase therapy. Overall, streptokinase and rt-PA seem to cause similar improvements in left ventricular function in this age group. Patency of occluded coronary arteries appears to be achieved in a high percentage of elderly patients following streptokinase therapy, based on a small sample. Thus, in view of the extensive clinical experience that now exists, intravenous streptokinase represents an appropriate alternative in elderly patients with acute myocardial infarction, and may be considered a first-line therapy in selected individuals, such as those with multiple risk factors for stroke or who present later than 6 hours after infarct.(ABSTRACT TRUNCATED AT 400 WORDS)
已将链激酶应用于成千上万患有急性心肌梗死的老年患者。大型随机试验结果提供了令人信服的证据,表明静脉注射链激酶能使该人群亚组在心肌梗死后获得明显的生存益处。安慰剂对照的ISIS - 2研究表明,60至69岁接受链激酶治疗的患者每1000人5周绝对死亡率降低38例,而年龄小于60岁的患者每1000人仅降低16例。如ISIS - 2试验所示,链激酶与阿司匹林联合使用可进一步降低死亡率,60至69岁接受该治疗方案的患者每1000人5周绝对死亡率降低70例。理想情况下,患者应在症状出现后尽快接受链激酶治疗,但在疼痛发作后长达12小时就诊的患者中也观察到了后期益处,老年人常常如此。实际上,在GUSTO试验中梗死6小时后接受治疗的患者中,链激酶的死亡率低于加速重组组织型纤溶酶原激活剂(rt - PA)。然而,与先前大型试验中链激酶和常规使用的rt - PA对总体生存的类似影响不同,GUSTO研究表明,在老年人和总体患者人群中,加速rt - PA的死亡率低于链激酶。与链激酶治疗相关的最常见不良反应是出血并发症,在GISSI - 1和ISIS - 2试验的总体人群中,严重出血(需要输血)的发生率为0.4%,轻微出血的发生率为3.6%。在GUSTO和其他主要死亡率试验中,rt - PA出现的中风过多,尤其是出血性中风,这肯定了链激酶作为该并发症风险增加的老年人的合适选择。链激酶治疗后的老年患者观察到收缩末期容积和局部室壁运动指数值显著降低。总体而言,链激酶和rt - PA在该年龄组中似乎对左心室功能有类似的改善作用。基于少量样本,链激酶治疗后,相当高比例的老年患者闭塞冠状动脉实现了再通。因此,鉴于目前已有的广泛临床经验,静脉注射链激酶是老年急性心肌梗死患者的合适替代方案,对于某些个体,如具有多种中风危险因素或梗死6小时后就诊的患者,可考虑作为一线治疗。(摘要截选至400字)