Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension

Background: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals. Methods: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90mmHg) were randomized to perindopril 5mg/indapamide 1.25 mg/amlodipine 5mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4mg/ indapamide 1.25 mg plus amlodipine 5mg (Per/Ind R Aml) for 6months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM). Results: A total of 532 patients were randomized: Per/Ind/Aml (n=262) and Per/Ind R Aml (n=269). Overall, the mean (SD) age was 55.78.8years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2mmHg. Systolic BP decreased in both groups at 2months from baseline: -14.9914.46mmHg Per/Ind/Aml versus -14.49 12.87mmHg Per/Ind RAml. A predefined noninferiority margin of 4mmHg was observed (P<0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24h. Both treatments were well tolerated. Conclusions: Per/Ind/Aml is an effective substitute for Per/ Ind R Aml, providing at least equivalent BP control over 24h in a single pill, with comparable safety.