Rees Karen, Stowe Rebecca, Patel Smitaa, Ives Natalie, Breen Kieran, Ben-Shlomo Yoav, Clarke Carl E
Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
Cochrane Database Syst Rev. 2011 Nov 9(11):CD008535. doi: 10.1002/14651858.CD008535.pub2.
Current treatment for Parkinson's disease (PD) is focused on relieving symptoms, at present there is nothing that is widely accepted to halt or slow disease progression. Potential neuroprotective or disease modifying agents have been identified from preclinical studies. One such group of compounds are anti-hypertensive drugs.
Electronic databases including trial registers were searched, complemented with handsearching of conference proceedings and searching the citations of key articles (updated May 2011). Authors were contacted, to provide additional information, where necessary.
For the primary prevention review, primary prevention trials and observational studies (cohort and case control studies) were sought. Participants were free of PD when exposure to anti-hypertensive drugs was assessed. For the secondary prevention review, clinical trials in patients with well defined PD were sought. Two people independently selected studies for inclusion using predetermined criteria.
Data were abstracted from the source papers and methodological quality was assessed independently by two review authors. Results for both reviews were dealt with descriptively.
Two cohort studies and four case control studies met the inclusion criteria for the primary prevention review. The two cohort studies found no effect of exposure to calcium channel blockers on the risk of developing PD. Three case control studies looked at the effects of exposure to calcium channel blockers and beta blockers on the risk of developing PD but the assessment periods of exposure were markedly different prior to PD onset, and different subclasses of drugs were examined, so results were not comparable. A protective effect of centrally acting calcium channel blockers was found in one study.Two trials and one ongoing trial met the inclusion criteria for the secondary prevention review. Each completed trial examined a different class of anti-hypertensive drug. The ongoing trial is examining the effects of the calcium channel blocker isradipine on motor symptoms and disease progression. It follows an earlier tolerability study. The results are due in the year 2012.Adverse effects were noted in all included trials and included intolerability to the drugs and worsening PD symptoms.
AUTHORS' CONCLUSIONS: There is currently a lack of evidence for the use of antihypertensive drugs for either the primary or secondary prevention of PD. More observational studies are required to identify potential drugs to go forward for safety and tolerability studies in people with early PD. The results of the ongoing trial will help inform further research.
帕金森病（PD）目前的治疗主要集中在缓解症状，目前尚无被广泛认可的能够阻止或减缓疾病进展的方法。临床前研究已确定了一些潜在的神经保护或疾病修饰药物。其中一类化合物是抗高血压药物。
1）抗高血压药物能否预防PD的发生？（一级预防）2）抗高血压药物是否为PD的疾病修饰药物，在PD确诊后能否减缓疾病进展？（二级预防）3）PD患者服用抗高血压药物有哪些不良反应？
检索了包括试验注册库在内的电子数据库，并辅以会议论文集的手工检索以及关键文章的参考文献检索（2011年5月更新）。必要时与作者联系以获取更多信息。
对于一级预防综述，寻找一级预防试验和观察性研究（队列研究和病例对照研究）。在评估抗高血压药物暴露时，参与者无PD。对于二级预防综述，寻找明确诊断为PD的患者的临床试验。两人使用预定标准独立选择纳入研究。
从原始论文中提取数据，两名综述作者独立评估方法学质量。两项综述的结果均采用描述性处理。
两项队列研究和四项病例对照研究符合一级预防综述的纳入标准。两项队列研究发现，暴露于钙通道阻滞剂对患PD的风险无影响。三项病例对照研究观察了暴露于钙通道阻滞剂和β受体阻滞剂对患PD风险的影响，但在PD发病前的暴露评估期明显不同，且研究的药物亚类不同，因此结果不可比。一项研究发现中枢性钙通道阻滞剂有保护作用。两项试验和一项正在进行的试验符合二级预防综述的纳入标准。每项完成的试验研究了不同类别的抗高血压药物。正在进行的试验正在研究钙通道阻滞剂伊拉地平对运动症状和疾病进展的影响。该试验是在早期耐受性研究之后进行的。结果将于2012年公布。所有纳入试验均注意到不良反应，包括对药物不耐受和PD症状恶化。
目前缺乏抗高血压药物用于PD一级或二级预防的证据。需要更多的观察性研究来确定潜在药物，以便在早期PD患者中进行安全性和耐受性研究。正在进行的试验结果将有助于为进一步研究提供信息。
