阿利吉仑在联合降压治疗中安全性的系统评价

Safety of aliskiren in combination therapy of hypertension:a systematic review

目的系统评价阿利吉仑联合降压药物治疗原发性高血压的安全性。方法计算机检索Cochrane Library、PubMed、中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）、万方数据库等数据库，检索时限均为从建库至2013年4月，纳入阿利吉仑联合降压药物治疗原发性高血压安全性的随机对照试验。由两位研究者按照纳入与排除标准独立筛选文献、提取资料和评价质量后，采用Revman5．1软件进行荟萃分析。结果共纳入12个研究，高血压患者8346例。纳入研究均采用随机双盲。阿利吉仑联合降压药物方案与所联合降压药物方案在总不良反应发生率、严重不良反应发生率和因不良反应停药等方面差异无统计学意义（分别OR=0．97，95％C10．89～1．07；OR=0．85，95％C10．51～1．41；OR=1．14，95％C10．86～1．52；均P〉0．05）。临床不良反应显示，阿利吉仑联合降压方案的头痛发生率低于对照组（OR=0．66，95％CI0．54～0．82，P〈O．05）；而两组间头晕、鼻咽炎、疲倦、腹泻、咳嗽和恶心的发生率差异无统计学意义。实验室指标显示，阿利吉仑联合降压方案血钾〉5．5mmol／L及血肌酐〉176．8μmol／L发生率高于对照组（分别OR=1．79，95％CI1．16～2．78；OR=2．83，95％CI1．03～7．82；均P〈0．05）；血钾〈3．5mmol／L发生率低于对照组（OR=0．45，95％C10．35～0．59，P〈0．05）；血钾≥6．0mmol／L及血尿素氮〉14．3mmol／L发生率与对照组差异无统计学意义。结论阿利吉仑联合降压方案与所联合药物单独治疗的总不良反应及严重不良反应相当，在肾功能及血钾异常时慎用阿利吉仑联合降压方案。

Objective To investigate the safety of aliskiren in the combination therapy of essential hypertension （EH）. Methods The relevant data from the database founding time to April 2013 in Cochrane Library, PubMed, Chinese Biomedical Literature Database, Chinese Scientific Journals Full text Database and Wanfang Database were retrieved by computer and applied to this study, ＂randomized controlled trials on the combination of aliskiren and an- tihypertensive drug vs antihypertensive drug alone in the treatment of hypertension＂. Two reviewers independently screened the databases, extracted data and evaluated the quality of data retrieved. The Cochrane Collaboration＇s software RevMan 5. 1 was used for meta analysis. Results A total of 12 studies involving 8346 patients were in- cluded. All were random, double-blind studies. The results of meta-analysis suggested that, compared with anti- hypertensive drug therapy alone, the aliskiren plus antihypertensive drug regimen had similar rates of total adverse e- vent （OR=0.97, 95% CI O. 89-1.07, P〉0.05）, serious adverse event （OR=0.85, 95% CI O. 51-1.41, P〉 0.05） and discontinuations due to adverse events （OR=1. 14, 95% CI O. 86-1.52, P〉0.05）. The meta-analysis results of clinical adverse events indicated that the incidence of headache （OR = 0.66, 95% CI O. 54-0.82, P〈 0.05） was less in the aliskiren plus antihypertensive drug group, while no statistical differences were noted in the in- cidence of dizziness, nasopharyngitis, fatigue, diarrhea, cough and nausea. In the aliskiren plus antihypertensive drug group the incidences of potassium〉5.5 mmol/L （OR=I. 79, 95% CI 1.16-2.78, P〈0.05） and serum creatinine 〉176.8 μLmol/L （OR=2.83, 95% CI 1.03-7.82, P〈0.05） were higher, but the incidence of potassi- um%3.5 mmol/L （OR=0.45, 95%CI 0.35-0.59, P〈0.05） was lower. No statistic significant differences were found in the occurrence of potassium 96.0 mmol/L and blood urea nitrogen 〉14.3 mmol/L. Conclusions Thecombination of aliskiren and antihypertensive drug therapy has similar incidences of adverse events and serious adverse event as antihypertensive drug therapy alone. The combined therapy of aliskiren and antihypertensive drug regimen should be used with caution for patients with abnormal potassium level and kidney dysfunction.