Roberts R, Rogers W J, Mueller H S, Lambrew C T, Diver D J, Smith H C, Willerson J T, Knatterud G L, Forman S, Passamani E
Maryland Medical Research Institute, Baltimore 21210.
Circulation. 1991 Feb;83(2):422-37. doi: 10.1161/01.cir.83.2.422.
In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality.
在心肌梗死溶栓治疗（TIMI）II期试验中，患者接受静脉注射重组组织型纤溶酶原激活剂（rt-PA），并被随机分为保守治疗组或侵入性治疗组。在这项研究中，还对符合β受体阻滞剂治疗条件的患者评估了即刻与延迟β受体阻滞剂治疗的效果，这组患者共1434例，其中720例被随机分配到即刻静脉注射组，714例被分配到延迟组。在即刻静脉注射组中，在开始rt-PA治疗的2小时内给予美托洛尔（每2分钟静脉注射5mg，共6分钟，静脉注射总剂量为15mg，随后在最初24小时内每12小时口服50mg，此后每12小时口服100mg）。被分配到延迟组的患者在第6天口服美托洛尔50mg，每日2次，此后每日2次口服100mg。两组对该治疗的耐受性均良好，主要终点指标，即出院时静息整体射血分数平均为50.5%，两组几乎相同。两组的局部心室功能也相似。总体而言，即刻静脉注射组和延迟组之间的死亡率没有差异，但在定义为低风险的亚组中，接受即刻β受体阻滞剂治疗的患者在6周时无死亡，而延迟β受体阻滞剂治疗的患者中有7例死亡。亚组中这一次要终点的这些发现被认为不足以支持关于临床应用的推荐。即刻静脉注射组在6天时再梗死发生率较低（2.7%对5.1%，p = 0.02），复发性胸痛发生率也较低（18.8%对24.1%，p＜0.02）。因此，在合适的心肌梗死后患者中，β受体阻滞剂在溶栓治疗后早期给予是安全的，并且与第一周内心肌缺血和再梗死的减少相关，但在改善心室功能或降低死亡率方面，与晚期给药相比并无益处。
