Effects of the concomitant administration of xanthine oxidase inhibitors with zofenopril or other ACE-inhibitors in postmyocardial infarction patients: a metaanalysis of individual data of four randomized, double-blind, prospective studies
Effects of the concomitant administration of xanthine oxidase inhibitors with zofenopril or other ACE-inhibitors in postmyocardial infarction patients: a metaanalysis of individual data of four randomized, double-blind, prospective studies
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DOI：
10.1186/s12872-018-0800-x
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发表时间：
2018-06-05
影响因子：
2.1
通讯作者：
Ambrosioni, Ettore
中科院分区：
文献类型：
--
作者：
Borghi, Claudio;Omboni, Stefano;Ambrosioni, Ettore
背景：急性心肌梗死（AMI）高尿酸血症患者的氧化应激增加。使用巯基ACE抑制剂（ACEIs），如佐芬普利或卡托普利，加上黄嘌呤氧化酶抑制剂（XOIs），可能会导致增强抗氧化作用和改善survival.Objective：我们验证了这样的组合的好处，在一个随机分层样本的3630后AMI患者的四个随机前瞻性SMILE（心肌梗死长期生存评估）研究。研究方法：165例（31.4%）患者接受XOI治疗（79例接受佐芬普利治疗，86例接受安慰剂、赖诺普利或雷米普利治疗），而360例未接受XOI治疗（192例接受佐芬普利治疗，168例接受安慰剂或其他ACEI治疗）。在这四组中，我们分别估计了主要心血管事件的1年合并风险（MACE、死亡或因心血管原因住院）。在接受佐芬普利+XOI的患者中，MACE发生率为10.1%，在接受安慰剂或其他ACEI + XOI的患者中，MACE发生率为18.6%，在接受佐芬普利不含XOI的患者中，MACE发生率为13.5%，在接受安慰剂或其他ACEI的患者中，MACE发生率为22.0%，但无XOI（各组间p = 0.034）。佐芬普利+XOI治疗组的无MACE生存率显著高于无XOI的其他ACEIs治疗组[风险比：2.29（1.06 - 4.91），p = 0.034]。与佐芬普利单药相比，观察到佐芬普利+XOI联合用药的优效性无显著趋势[1.19（0.54 - 2.64），p = 0.669]或与安慰剂或其他ACEI + XOI [1.82（0.78 - 4.26），p = 0.169]。我们的回顾性分析表明，AMI后患者联合使用具有抗氧化活性的降尿酸药物和ACEI，用佐芬普利观察到最佳效果。
Background: 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.Objective: 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. Methods: 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).Results: 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].Conclusions: 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.