Ye R, Hu Y, Yao A, Yang Y, Shi Y, Jiang Y, Zhang J
Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China.
Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.
Int J Clin Pract. 2015 Jun;69(6):674-81. doi: 10.1111/ijcp.12626. Epub 2015 Feb 27.
The impacts of renin-angiotensin system (RAS)-targeting antihypertensive drugs on Alzheimer's disease (AD) remain controversial. We performed this meta-analysis to evaluate the precise value of RAS-targeting antihypertensive drugs in terms of attenuating incidence of AD and slowing down cognitive decline in patients with AD.
A systematic literature search was conducted using PubMed, Embase, ScienceDirect and CBM (China Biology Medicine Disc) before September 2014. Studies analysing incidence of AD and cognitive changes in AD patients with RAS-targeting antihypertensive drugs were identified. The principal outcome measures were hazard ratios (HRs) for incidence of AD and standardised mean difference (SMD) for cognitive changes in AD patients. Pooled data were calculated using fixed or random effects models according to the heterogeneity.
In total, 12 studies involving 896,410 participants met our inclusion criteria. RAS-targeting antihypertensive drugs were significantly associated with a reduced incidence rate of AD (HR 0.81, 95% CI 0.72-0.92, p = 0.001). In subgroup analysis, both angiotensin renin blockers and angiotensin converting enzyme inhibitors were shown to effectively decrease the incidence rate of AD. In the analysis of cognitive changes, a slower rate of cognitive decline was observed in AD patients with RAS-targeting antihypertensive drug (SMD 0.30, 95% CI 0.09-0.50, p = 0.004), when randomised trials and observational trials were combined. However, analysis of randomised trials alone did not show the same result (SMD 0.20, 95% CI -0.10 to 0.50, p = 0.182).
Renin-angiotensin system-targeting antihypertensive drugs may be a potential treatment for reducing the incidence and progression of AD. Further studies on RAS-targeting antihypertensive drugs, especially large randomised clinical trials, should be conducted in the future.
肾素-血管紧张素系统(RAS)靶向性抗高血压药物对阿尔茨海默病(AD)的影响仍存在争议。我们进行了这项荟萃分析,以评估RAS靶向性抗高血压药物在降低AD发病率和减缓AD患者认知衰退方面的精确价值。
2014年9月之前,使用PubMed、Embase、ScienceDirect和CBM(中国生物医学文献数据库)进行了系统的文献检索。纳入分析RAS靶向性抗高血压药物对AD患者AD发病率及认知变化的研究。主要结局指标为AD发病率的风险比(HRs)和AD患者认知变化的标准化均数差(SMD)。根据异质性,使用固定效应模型或随机效应模型计算合并数据。
共有12项研究、896,410名参与者符合我们的纳入标准。RAS靶向性抗高血压药物与AD发病率降低显著相关(HR 0.81,95%CI 0.72 - 0.92,p = 0.001)。亚组分析显示,血管紧张素肾素阻滞剂和血管紧张素转换酶抑制剂均能有效降低AD发病率。在认知变化分析中,当将随机试验和观察性试验合并时,使用RAS靶向性抗高血压药物的AD患者认知衰退速度较慢(SMD 0.30,95%CI 0.09 - 0.50,p = 0.004)。然而,仅对随机试验进行分析时未显示出相同结果(SMD 0.20,95%CI -0.10至0.50,p = 0.182)。
RAS靶向性抗高血压药物可能是降低AD发病率和进展率的一种潜在治疗方法。未来应进一步开展针对RAS靶向性抗高血压药物的研究,尤其是大型随机临床试验。