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摘要: 血管紧张素受体-脑啡肽酶抑制剂(ARNI)是近些年推出的作用于射血分数减低型心力衰竭患者的一类新型药物，包含缬沙坦和沙库巴曲2种成分，可同时作用于肾素-血管紧张素-醛固酮系统(RAAS)和利钠肽系统(NPS)，发挥利尿、利钠、舒张血管、拮抗RAAS等作用。新近研究发现，ARNI也可用于高血压治疗，对高血压及其并发症均有显著作用。本文就ARNI对高血压及其有关的心力衰竭、冠状动脉疾病及肾脏疾病等并发症的作用及地位作一综述。
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关键词:
- 高血压 /
- 血管紧张素受体-脑啡肽酶抑制剂 /
- 并发症
Abstract: Angiotensin receptor-enkephalinase inhibitors (ARNIs) are the new type of drugs that act on heart failure with reduced ejection fraction. They contain two components, valsartan and sacubitril, which can act on both the renin-angiotensin-aldosterone system (RAAS) and the natriuretic peptide system (NPS). ARNI exerts diuretic, natriuretic, vasodilatory, and RAAS antagonistic effects. Recent studies have found that ARNI can also be used to treat hypertension and has a significant effect on hypertension and its complications. This article will review the role and status of ARNI in hypertension and its related complications such as heart failure, coronary artery disease, and renal disease.-
Key words:
- hypertension /
- angiotensin receptor-neprilysin inhibitor /
- complications
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表 1 LCZ696与高血压等心血管疾病研究汇总
Table 1. The studies of LCZ696 in hypertension and cardiovascular diseases
研究类别 研究对象 样本量/例 年龄/岁 对照组 随访时间/周 主要结果 LCZ696不良事件发生率/% LCZ696与高血压相关研究 Ruilope等[13] 轻中度高血压 1328 18~75 缬沙坦和安慰剂 8 LCZ696对比相应剂量缬沙坦：血压平均降低4.20/2.17 mmHg(P < 0.05) < 30.00 Kario等[14] 轻中度高血压 389 ≥18 安慰剂 8 LCZ696血压控制率(<140/90 mmHg)为50%左右，显著高于安慰剂(15.2%) 约38.00 Supasyndh等[15] 轻中度高血压 341 ≥18 单臂 52 基于沙库巴曲/缬沙坦的降压方案总体血压控制率达75.3% 63.90 Wang等[16] 轻中度高血压 266 ≥18 安慰剂 8 与氨氯地平单药治疗相比，LCZ696/氨氯地平显著降低了24 h动态压(P < 0.001) 20.00 Kario等[17] 重度高血压 35 ≥18 单臂 8 第8周时血压降低达35.3/22.1 mmHg 48.60 Supasyndh等[19] 老年高血压 588 ≥65 奥美沙坦 14 第10周时LCZ696较奥美沙坦降压更明显(22.71 mmHg∶16.11 mmHg，P < 0.001) 47.60 Williams等[20] 老年收缩期高血压 454 ≥60 奥美沙坦 52 在降低动态中心主动脉收缩压和肱动脉收缩压方面LCZ696优于奥美沙坦(P < 0.001) 57.60 Wang等[22] 盐敏感高血压 72 ≥18 缬沙坦 8 LCZ696通过利尿利钠达到更好的血压控制作用，血压波动较小，夜间动态血压降低的尤为明显 32.40 LCZ696与高血压并发症等相关研究 Balmforth等[25] HFrEF 8399 ≥18 依那普利 108 LCZ696在降低心衰再住院率及全因死亡率方面显著优于依那普利，且不受病因影响 46.09 Solomon等[26] HFpEF 4822 ≥50 缬沙坦 140 与缬沙坦相比，LCZ696的主要结局事件较少，但无统计学差异；LCZ696降低了冠状动脉复合结局风险；LCZ696具有肾脏保护作用 58.87 Rezq等[31] STEMI 200 18~90 雷米普利 24 6个月时，LCZ696与雷米普利组主要心脏不良事件20%∶38%(OR=0.42，95%CI：0.23~0.78，P=0.005) 未观察到不良事件 Ito等[34] 高血压合并中重度肾功能不全 56 ≥20 单臂 8 LCZ696在日本高血压和肾功能不全患者中血压平均降低分别为20.5/8.3 mmHg，尿白蛋白/肌酐比平均降低为15.1% 43.80 Zhang等[36] 载脂蛋白E缺陷小鼠 72 / 对照组和缬沙坦组 12 LCZ696较对照组及缬沙坦组更能抑制炎症反应及动脉粥样硬化 / Martens等[38] HFrEF 151 未提及 单臂 52 LCZ696可减少室性心律失常的发生 / Jordan等[39] 肥胖高血压 98 ≥18 氨氯地平 8 LC696较氨氯地平更能增加外周胰岛素敏感性及腹部脂肪分解 60.00 
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