Plosker G L, McTavish D
Adis International Limited, Auckland, New Zealand.
Drugs Aging. 1995 Sep;7(3):226-53. doi: 10.2165/00002512-199507030-00007.
Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58,000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50 mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50 mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients.(ABSTRACT TRUNCATED AT 400 WORDS)
卡托普利是一种血管紧张素转换酶（ACE）抑制剂，已广泛用于治疗高血压和充血性心力衰竭患者。近年来，动物和人体研究表明，卡托普利可减轻心肌梗死后发生的左心室重塑（结构改变和扩大），而这可能导致左心室功能障碍和死亡风险增加。随后，大型临床试验表明，急性心肌梗死后接受卡托普利或其他ACE抑制剂（除标准治疗外）的患者死亡率和发病率降低。第四次国际心肌梗死生存研究（ISIS-4）是一项析因试验，随机纳入了超过58000名患者，结果表明，在心肌梗死后24小时内开始使用卡托普利，并滴定至每日两次、每次50毫克，持续1个月，与安慰剂相比，随机分组后5周时总体死亡率显著降低（7.19%对7.69%；p = 0.02）。这相当于在此期间每1000名接受卡托普利治疗的患者中有5人获救。此外，梗死1年后生存优势似乎仍得以维持。尽管ISIS-4试验纳入了高风险和低风险患者，但卡托普利对死亡率较高风险患者（如伴有心力衰竭体征或既往梗死的患者）的生存益处最大。在生存与心室扩大（SAVE）研究中，急性心肌梗死后接受卡托普利治疗的左心室功能障碍患者（但无明显心力衰竭或持续性缺血）总体死亡率相对显著降低19%。卡托普利在心肌梗死后3至16天开始使用，并滴定至每日三次、每次50毫克，平均持续42个月。在此高风险患者组中，在此期间每1000名接受卡托普利治疗的患者中约有40至50人获救。这与其他大型随机试验中高风险患者急性心肌梗死后使用其他ACE抑制剂所显示的生存益处相似。使用SAVE试验数据进行的成本效益分析表明，卡托普利与用于心肌梗死幸存者的其他干预措施相比具有优势。总体而言，在SAVE、ISIS-4及该临床背景下的其他研究中，患者对卡托普利耐受性良好。因此，急性心肌梗死后在标准治疗基础上加用卡托普利，早期或晚期给药均可提高生存率并降低心血管疾病发病率，尤其是在特定的高风险患者中。（摘要截选至400词）
