阿利沙坦酯联合利尿剂或钙通道阻滞剂对单药治疗未达标高血压患者的疗效及安全性

Effects and safety of allisartan isoproxil combined with diuretics or calcium channel blocker in patients with hypertension who failed allisartan monotherapy

目的评价我国自主研发的一种新型的选择性非肽类血管紧张素受体阻滞药(ARB)1.1类口服降压药阿利沙坦酯联合氨氯地平或联合吲达帕胺,在单药治疗未达标的轻中度原发性高血压(EH)患者中的临床疗效及安全性。方法2016年9月9日至2018年12月7日,在全国44家研究中心选择年龄18~75岁、体质量指数(BMI)18.5~30.0 kg/m^(2)、血压140/90~<180/110 mm Hg的EH患者。给予阿利沙坦酯片240 mg/d,用药4周后评估血压是否达标,达标者继续用药8周,未达标者1∶1随机分配到阿利沙坦酯片240 mg+吲达帕胺缓释片1.5 mg组(A+D)或阿利沙坦酯片+苯磺酸氨氯地平片5 mg组(A+C)治疗8周。主要观察治疗12周坐位血压降低幅度和达标率(坐位血压<140/90 mm Hg)以及安全性指标。结果共入选2212例患者,其中纳入疗效分析共2126例,平均年龄(55.1±10.2)岁。疗效结果显示,1463例阿利沙坦酯单药治疗4周有效(68.8%),坐位收缩压/舒张压较基线降低(14.7±12.2)/(8.0±8.4)mm Hg(P<0.001)。不达标者在阿利沙坦酯基础上联合氨氯地平或联合吲达帕胺治疗8周后,联合氨氯地平组相较于单药治疗4周时的收缩压和舒张压分别降低(14.0±12.2)/(8.3±9.2)mm Hg,达标率为57.7%(169/293);联合吲达帕胺组与单药治疗4周时相比,收缩压/舒张压下降(14.4±12.1)/(8.2±8.2)mm Hg,达标率为62.8%(181/288)。联合吲达帕胺组与联合氨氯地平组相比,血压降幅和达标率均相当,差异无统计学意义。不良反应发生率联合氨氯地平组为8.7%,联合吲达帕胺组为11.7%。结论阿利沙坦酯单药治疗未达标联合吲达帕胺或联合氨氯地平,可进一步提高达标率,2组间达标及疗效相同,安全性相当。

Objective To primarily evaluate the effects and safety of a novel selective non peptide angiotensinⅡtype 1(AT1)receptor blocker(ARB)1.1 oral antihypertensive drug allisartan isoproxil combined with amlodipine or indapamide in the treatment of patients with essential hypertension(EH)who failed allisartan monotherapy.Methods Patients aged 18-75 years with body mass index(BMI)18.5-30.0 kg/m^(2),diagnosed with mild-to-moderate EH[office systolic blood pressure(SBP)140-<180 and/or office diastolic blood pressure(DBP)90-<110 mm Hg]in 44 study centres between September 9,2016 and December 7,2018 were included.Allisartan isoproxil tablet 240 mg was administered per day for 4 weeks,then the same treatment continued for 8 weeks if office blood pressure(BP)achieved the target of SBP/DBP<140/90 mm Hg;while the non-achievers were 1∶1 randomly divided into two groups(A+D:allisartan isoproxil 240 mg+indapamide sustained-release tablet 1.5 mg,or A+C:allisartan isoproxil 240 mg+amlodipine besylate 5 mg)for further 8-week combined therapy.The BP target achieving rate,reduction of sitting blood pressure from baseline,safety and compliance were evaluated as the primary efficacy endpoint.Results A total of 2212 patients were enrolled,among them 2126 patients were included in the efficacy analysis,with an average age of(55.1±10.2)years.A total of 1463 cases(68.8%)were effective after 4 weeks allisartan isoproxil treatment,and the mean SBP and DBP levels were significantly decreased by(14.7±12.2)and(8.0±8.4)mm Hg compared with the baseline levels(all P<0.001).The sitting BP levels(SBP/DBP)has significantly decreased by(14.0±12.2)/(8.3±9.2)mm Hg respectively after 8 weeks of allisartan isoproxil combined with indapamide(A+C)compared with 4 weeks monotherapy with allisartan isoproxil,BP targeting rate was 57.7%(169/293);In the group of A+D,the SBP/DBP has significantly decreased by(14.4±12.1)/(8.2±8.2)mm Hg respectively,BP targeting rate was 62.8%(181/288).The differences between two groups in the reduction of BP and BP targeting rate were no statistical significance.The incidence of adverse reactions was 8.7%in the group of A+C and 11.7%in the group of A+D.Conclusion Allisartan isoproxil combined with indapamide and amlodipine can further improve the BP targeting rate when allisartan monotherapy failed in EH,both have the similar efficacy and safety.