Lancet. 1994 May 7;343(8906):1115-22.
GISSI-3 is a multicentre randomised clinical trial to assess the efficacy of lisinopril, transdermal glyceryl trinitrate (GTN), and their combination in improving survival and ventricular function after acute myocardial infarction (AMI). Between June, 1991, and July, 1993, 19,394 patients were randomised from 200 coronary care units in Italy. Eligible patients presented within 24 h of symptom onset and had no clear indications for or against the study treatments. In a factorial design patients were randomly assigned 6 weeks of oral lisinopril (5 mg initial dose and then 10 mg daily) or open control as well as nitrates (intravenous for the first 24 h followed by transdermal GTN 10 mg daily) or open control. Complete clinical data and 6-week follow-up were available for 18,895 (97.4%) patients randomised. Two-dimensional echocardiographic data were available for 14,209 patients. Overall 6-week mortality was 6.7%. Lisinopril, started within 24 h from AMI symptoms, produced significant reductions in overall mortality (odds ratio 0.88 [95% CI 0.79-0.99]) and in the combined outcome measure of mortality and severe ventricular dysfunction (0.90 [0.84-0.98]). In the same trial the systematic administration of transdermal GTN did not show any independent effect on the same outcome measures (0.94 [0.84-1.05] and 0.94 [0.87-1.02]). Systematic combined administration of lisinopril and GTN also produced significant reductions in overall mortality (0.83 [0.70-0.97]) and in the combined endpoint (0.85 [0.76-0.94]). The favourable effect of lisinopril alone or with GTN was clear also in the predefined high-risk populations (elderly patients and women) for the combined endpoint. These findings were obtained in a population intensively exposed to recommended treatments (thrombolysis 72%, beta-blockade 31%, and aspirin 84%); non-protocol treatment with angiotensin-converting-enzyme inhibitors and nitrates was allowed for specific clinical indications. No excess of unfavourable clinically relevant events in the treated groups was reported.
GISSI-3是一项多中心随机临床试验，旨在评估赖诺普利、经皮硝酸甘油（GTN）及其联合用药对改善急性心肌梗死（AMI）后生存率和心室功能的疗效。1991年6月至1993年7月期间，意大利200个冠心病监护病房的19394例患者被随机分组。符合条件的患者在症状出现后24小时内就诊，且没有明确的研究治疗适应证或禁忌证。采用析因设计，患者被随机分配接受6周的口服赖诺普利（初始剂量5mg，然后每日10mg）或开放对照，以及硝酸盐类药物（最初24小时静脉给药，随后每日经皮给予GTN 10mg）或开放对照。18895例（97.4%）随机分组患者获得了完整的临床数据和6周随访结果。14209例患者获得了二维超声心动图数据。6周总死亡率为6.7%。在AMI症状出现后24小时内开始使用赖诺普利，可显著降低总死亡率（比值比0.88[95%CI 0.79 - 0.99]）以及死亡率和严重心室功能障碍的联合结局指标（0.90[0.84 - 0.98]）。在同一试验中，经皮GTN的系统性给药对相同结局指标未显示任何独立作用（0.94[0.84 - 1.05]和0.94[0.87 - 1.02]）。赖诺普利和GTN的系统性联合给药也可显著降低总死亡率（0.83[0.70 - 0.97]）和联合终点指标（0.85[0.76 - 0.94]）。对于联合终点指标，单独使用赖诺普利或与GTN联合使用的有益作用在预先定义的高危人群（老年患者和女性）中也很明显。这些发现是在大量接受推荐治疗的人群中获得的（溶栓治疗72%、β受体阻滞剂治疗31%、阿司匹林治疗84%）；对于特定临床适应证，允许使用血管紧张素转换酶抑制剂和硝酸盐类药物进行非方案治疗。未报告治疗组出现任何过量的不良临床相关事件。
