Borghi Claudio, Omboni Stefano, Reggiardo Giorgio, Bacchelli Stefano, Esposti Daniela Degli, Ambrosioni Ettore
Unit of Internal Medicine, Policlinico S. Orsola, University of Bologna, Bologna, Italy.
Divisione di Medicina Interna, Policlinico S.Orsola, Via Massarenti 9, 40138, Bologna, Italy.
BMC Cardiovasc Disord. 2018 Jun 5;18(1):112. doi: 10.1186/s12872-018-0800-x.
Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival.
We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies.
One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes).
MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p = 0.034 across groups). Rate of survival free from MACE was significantly larger under treatment with zofenopril + XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06-4.91), p = 0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54-2.64), p = 0.669] or vs. placebo or other ACEIs + XOIs [1.82 (0.78-4.26), p = 0.169].
Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.
急性心肌梗死（AMI）的高尿酸血症患者氧化应激增加。使用含巯基的血管紧张素转换酶抑制剂（ACEI），如佐芬普利或卡托普利，加黄嘌呤氧化酶抑制剂（XOI），可能会增强抗氧化作用并提高生存率。
我们在四项随机前瞻性SMILE（心肌梗死长期生存评估）研究的3630例AMI后患者的随机分层样本中，验证了这种联合用药的益处。
165例（31.4%）患者接受XOI治疗（79例使用佐芬普利，86例使用安慰剂、赖诺普利或雷米普利），而360例未接受XOI治疗（192例使用佐芬普利，168例使用安慰剂或其他ACEI）。在这四组中，我们分别估计了主要心血管事件（MACE，心血管原因导致的死亡或住院）的1年联合风险。
接受佐芬普利+XOI治疗的患者中MACE发生率为10.1%，接受安慰剂或其他ACEI+XOI治疗的患者中为18.6%，接受佐芬普利但未接受XOI治疗的患者中为13.5%，接受安慰剂或其他ACEI但未接受XOI治疗的患者中为22.0%（各组间p=0.034）。接受佐芬普利+XOI治疗时无MACE的生存率显著高于接受其他未使用XOI的ACEI治疗时[风险比：2.29（1.06-4.91），p=0.034]。观察到佐芬普利+XOI联合用药相对于单独使用佐芬普利[1.19（0.54-2.64），p=0.669]或相对于安慰剂或其他ACEI+XOI[1.82（0.78-4.26），p=0.169]有不显著的优势趋势。
我们的回顾性分析表明，在AMI后患者中，使用具有抗氧化活性的降尿酸药物与ACEI联合治疗可提高无MACE的生存率，佐芬普利的效果最佳。
