Efficacy and Safety of Fixed-Dose Perindopril Arginine/Amlodipine in Hypertensive Patients Not Adequately Controlled with Amlodipine 5 mg or Perindopril <b><i>tert</i></b>-Butylamine 4 mg Monotherapy

Abstract

Objectives: To assess the blood pressure-lowering efficacy and tolerability of perindopril/amlodipine fixed-dose combinations in Chinese patients with mild-to-moderate essential hypertension not adequately controlled with monotherapy alone. Methods: In 2 separate double-blind studies, patients received a 4-week run-in monotherapy of amlodipine 5 mg or perindopril 4 mg, respectively. Those whose blood pressure was uncontrolled were then randomized to receive the fixed-dose combination of perindopril 5 mg/amlodipine 5 mg (Per/Amlo group) or remain on the monotherapy for 8 weeks. Patients who were uncontrolled at the week 8 (W8) visit were up-titrated for the Per/Amlo combination, or received additional treatment if on monotherapy, for a further 4 weeks. The main efficacy assessment was at 8 weeks. Results: After 8 weeks, systolic blood pressure (SBP; primary criterion) was statistically significantly lower in the Per/Amlo group (vs. Amlo 5 mg, p = 0.0095; vs. Per 4 mg, p < 0.0001). Uncontrolled patients at W8 who received an up-titration of the Per/Amlo combination showed a further SBP reduction. These changes were mirrored by reassuring reductions in diastolic blood pressure. The fixed-dose combinations were well tolerated. Conclusions: Single-pill combinations of perindopril and amlodipine provide hypertensive patients with a convenient and effective method of reducing blood pressure.

Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review

“…After 8 weeks, the mean SBP in the perindopril/amlodipine FDC (5/5 mg) showed a mean reduction of 11.1 ± 11.9 mmHg compared to a mean reduction of 8.5 ± 11.1 mmHg SBP in the amlodipine 5-mg group ( p = 0.0095). Mean SBP decreased to 15.8 ± 12.1 mmHg in the perindopril/amlodipine FDC group compared with 7.8 ± 13.7 mmHg in the perindopril 4-mg group ( p < 0.0001) ( Hu et al, 2016 ).…”

“…There were 14 studies that reported the safety of perindopril/amlodipine FDC ( Supplementary Table S2 ). Of these, several serious but rare emergent adverse events (EAEs) of perindopril/amlodipine FDC have been reported, including stroke, brain infarction, cataracts, and diaphragmatic eventration ( Hu et al, 2016 ). In the study by Fleig et al, eight patients (0.4%) experienced severe EAEs in 140 ADR of 88 patients, of which four patients (0.2%) did not recover and one patient died with a hypertensive crisis ( Fleig et al, 2018 ).…”

“…EAEs that were not serious, including dry cough, ankle and lower extremity edema, facial flushing, hypotension, constipation, and allergy, may have resulted in some patients withdrawing from the study ( Manolis et al, 2015 ; Hu et al, 2016 ; Vlachopoulos et al, 2016 ). The majority of EAEs were more frequent, and some were more severe than the comparison group.…”

“…The rates of reported side effects in the included studies were relatively low, spanning a range of 1.8%–18.9% ( Bansal et al, 2014 ; Laurent et al, 2015 ). Cough were reported as the most frequent adverse events associated with the use of perindopril/amlodipine FDC, ranged from 4.6% to 9.0% ( Hu et al, 2016 ). Most patients tolerate cough when continuing treatment, with only a few requiring discontinuations.…”

Efficacy of single‐pill combination in uncontrolled essential hypertension: A systematic review and network meta‐analysis

“…Eleven SPC were compared, namely Amlodipine/valsartan (8 studies), 12,[21][22][23][24][25][26][27] Telmisartan/amlodipine (5 studies), 13,[28][29][30][31] Losartan/HCTZ (4 studies), [32][33][34][35] Candesartan/HCTZ (4 studies), 32,[36][37][38] Amlodipine/benazepril (3 studies), [39][40][41] Telmisartan/HCTZ (3 studies), 13,23,30 Valsartan/HCTZ (3 studies), 12,42,43 Irbesartan/amlodipine (2 studies), 44,45 Amlodipine/losartan (2 studies), 35,46 Irbesartan/HCTZ (1 studies), 47 Perindopril/amlodipine (1 studies). 48 The outcomes included were mainly systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate after treatment. The characteristics of the included studies are shown in Table 1.…”