双重肾素-血管紧张素系统抑制策略在心肾血管疾病中的应用价值

Application value of dual renin-angiotensin system inhibition strategies in cardiovascular and renal vascular diseases

肾素-血管紧张素系统(renin-angiotensin system,RAS)的抑制剂包括血管紧张素转换酶抑制剂(angiotensin-converting enzyme inhibitor,ACEIs)、血管紧张素Ⅱ受体拮抗剂(angiotensinⅡreceptor blocker,ARBs)和肾素抑制剂,都是心肾血管疾病的重要治疗药物。从药理机制上分析,联用上述药物(即双重RAS抑制的策略)对于心肾血管疾病的治疗可能有协同作用,并减少各自的不良反应。但前期一些临床研究报道显示双重RAS抑制方案对于很多心肾血管疾病的患者观察未发现显著受益,反而使高血钾、低血压和肾功能损伤的风险有所增加。因此欧洲和美国药品监督管理机构警告临床应慎重使用,但此警告对个体化用药保留了肯定,特别强调心力衰竭患者联合使用ACEI类和ARB类药物可能是有效的,联用的前提是密切监测患者的肾功能、电解质以及血压。基于上述原因,目前心血管疾病的临床指南往往对ACEIs和ARBs的联用持不推荐的态度。然而,临床上也确有证据显示低剂量的ACEsⅠ和ARBs联合使用可以获得更为有效的RAS阻断,且不良反应极少,尤其是在合并有蛋白尿的慢性肾脏病患者。

Renin-angiotensin system inhibitors(RASI)[including angiotensin-converting enzyme inhibitor(ACEIs),angiotensin Ⅱ receptor blocker(ARBs),renin inhibitors]are important therapeutic drugs for cardiovascular and renal vascular diseases.From the pharmacological mechanism analysis,the combination of the above drugs(the strategy of dual RAS blockade)may have synergistic effect on the treatment of cardiovascular and renal vascular diseases,and reduce their respective adverse reactions.However,some previous clinical studies showed that the dual RAS blockade did not significantly benefit patients with cardiovascular and renal vascular diseases,but increased the risk of hyperkalemia,hypotension and renal function damage.Therefore,the European and American drug regulatory agencies have warned that clinical use should be cautious,but this warning remains positive for individualized drug use,especially emphasizing that the combination of ACEI and ARB drugs in patients with heart failure may be effective,and the premise of the combination is to closely monitor the renal function,electrolyte and blood pressure of patients.Based on the above reasons,the current clinical guidelines for cardiovascular diseases often do not recommend the combination of ACEIs and ARBs.However,there were also evidence that low-dose ACEIs combined with ARBs can achieve more effective RAS blocking,and the adverse effects are rare,especially in patients with chronic kidney disease with proteinuria.