Successful perindopril/amlodipine+indapamide treatment as second line in uncontrolled hypertensive patients in line with european guidelines

Type of funding sources: Private company. Main funding source(s): The study was sponsored by Servier.

ESC/ESH guidelines recommend use of a RAAS inhibitor + CCB + Thiazide as second step treatment for hypertensive patients with uncontrolled blood pressure (BP), preferably as single-pill combination.

We investigated the results of adding indapamide SR 1.5 mg to the single-pill combination of perindopril/amlodipine (Per/Aml) in a context of a randomized double-blind controlled trial.

The study compared 2 treatment strategies over 6 months: initiation with Per/Aml with further conditional uptitration up to Per/Amlo 14/10 mg, followed after 3 months of bi-therapy by addition of indapamide SR 1.5 mg for 3 additional months, versus initiation with Valsartan (Val) and further addition of amlodipine, then uptitration up to Val/Amlo 160/10 mg. The study was completed by an additional 8-month extension period (M14) at the same dose for the patients controlled at M6, for safety purposes.

Compared with initiation of Val alone, initiation of treatment with Per/Amlo led to lower number of patients needing further uptitration at M3 (23% vs 31%). In 202 patients uncontrolled with Per/Amlo 14/10, the addition of indapamide SR 1.5 mg led to a large additional decrease in systolic BP (-14.8±13.3 mmHg) and diastolic BP (-7.2±9.7 mmHg) with BP control achieved in 82.5% of the patients (<140/90 mmHg) and BP response in 94%. During the whole period (11 months), 5.9% of the patients (n=10) discontinued the triple therapy due to 11 adverse reactions, versus 3.9% of those receiving Per/Amlo 14/10 over the same period.

These findings confirm the BP-lowering efficacy and safety of adding the thiazide-like indapamide to a previous ACE inhibitor+CCB (Per/Amlo) combination providing clinical evidence for this triple therapy, preferably to be given as single-pill combination.