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

Objective To primarily evaluate the effects and safety of a novel selective non peptide angiotensin Ⅱ type 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 2 212 patients were enrolled, among them 2 126 patients were included in the efficacy analysis, with an average age of（55.1±10.2） years. A total of 1 463 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.