8种血管紧张素转换酶抑制剂治疗高血压的临床疗效、安全性及成本效果评估

目的从循证医学角度评价国内8种血管紧张素转换酶抑制剂(普利类降压药)对高血压患者的临床疗效、安全性、成本-效果、依从性及伦理学等.方法采用药物卫生技术评估方法,检索Medline、Cochrane图书馆、Embase和中国生物医学文献数据库(CBMdisc)等数据库,疗效分析纳入系统评价、随机临床对照试验和交叉试验等;安全性和药物经济学分析同时纳入观察性研究.按国际评价标准严格评价文献,纳入高质量研究.结果8种普利类降压药的降压幅度与剂量呈正相关;任何一种普利类降压药与钙拮抗剂或利尿剂或受体阻滞剂联合应用,降压效果更佳;新型普利类降压药的作用强于依那普利和卡托普利.Meta-分析显示,谷-峰比值小于50%的有培哚普利、贝那普利和卡托普利.上述8种普利类降压药均有关于心脏保护的研究证据.慢性心力衰竭,依那普利和卡托普利的高质量研究证据最多;赖诺普利、培哚普利、西拉普利和贝那普利仅观察了中间指标对心力衰竭的影响.心脏保护,福辛普利较卡托普利更安全,比依那普利效果好;赖诺普利优于卡托普利等均以替代指标进行比较.治疗心肌梗死,证据显示卡托普利和赖诺普利可降低急性期(心肌梗死36 h内)患者病死率;依那普利、卡托普利、雷米普利和培哚普利可明显降低梗死后期(梗死后3 d服用)的总死亡率.仅雷米普利、赖诺普利和培哚普利有证据显示对脑血管具有保护作用.尚未发现有关贝那普利对肾脏的保护性研究,其他普利类药物在这方面的研究数量亦较少,但显示能在一定程度减少蛋白尿和延缓肾衰.新型普利类降压药的不良反应与卡托普利相似,但发生率略低.不良反应研究表明:雷米普利、培哚普利和贝那普利的不良反应发生率少于卡托普利,患者对福辛普利的耐受性高于依那普利.有关普利类降压药的成本-效果研究文献不多,但有证据表明,依那普利治疗心力衰竭具有良好的成本-效果,且赖诺普利更好.雷米普利和卡托普利分别与钙拮抗剂或利尿剂联用,可降低治疗成本.缺乏普利类降压药在伦理学方面的研究证据.结论仅依据现有研究证据尚不能对8种普利降压药进行简单的总排序;并非每种普利类降压药都具有足够的心、脑、肾保护证据,临床医生在选择这8种普利类药物时,首先应选择该方面有足够研究证据的品种.

Health Technology Assessment of Eight ACEIs for Hypertension

Objective To evaluate the clinical effectiveness, safety, cost-effectiveness of eight angiotensin converting enzyme inhibitors(ACEIs) in order to provide evidence for adjustment of Essential Drug List in China. Method Collecting all clinical trials by searching Medline, Cochrane Library, Embase and Chinese Biomedical Database and conducting critical appraisal. High quality randomized controlled trials and systematic reviews were included to assess the effectiveness of ACEIs. Non-randomized controlled trials were also included to evaluate the safety and cost-effectiveness. Results New generation of ACEIs are better than enalapril and captopril in antihypertension and endurance. Meta-analysis showed that T/P ratio was less than 50% in prindopril, benazepril and captopril. Enalapril and captopril had the most adequate evidence in the treatment of chronic heart failure. The effects of lisinopril, prindopril, benazepril and cilazapril positive influence on heart failure were assessed by surrogates. Captopril, lisinopril could reduce the total death rate of acute period (during 36 hours of AMI). Enalapril, captopril, ramipril and prindopril had the effect of heart protection in late period of AMI (3 days after AMI). Only ramipril, lisinopril and prindopril had evidence to support the protective effect on cerebral vessels. The available evidence, though not adequate, showed all the ACEIs except benazepril could diminish proteinuria and delay the renal failure. The new generations of ACEIs were similar in adverse reactions to enalapril and captopril, while incidences were lower than enalapril and captopril. Few evidence on cost-effectiveness of ACEIs were identified. The available evidence showed enalapril was cost-effective in treating heart failure. However, it compromised to lisinopril. The studies on ethics were not available. Conclusions It was difficult to generally rank the eight ACEIs according to available evidence. Not all eight ACEIs had adequate evidence in organs protection. It was suggested that clinicians should select ACEIs with adequate evidence to treat patients on states.