Chronotherapy’s opportunities of a fixed combination of perindopril 10 mg/indapamide 2.5 mg in patients with a lack of night reduction in blood pressure

Currently, adequate reduction of blood pressure (BP) during the night in patients with arterial hypertension remains important problem. To study chronotherapy’s opportunities to achieve better BP control by a single dose of antihypertensive drugs while maintaining high compliance. Aim. To evaluate the efficacy, tolerability, safety of various prescription regimes of fixed combination: perindopril 10 mg and indapamide 2.5 mg in patients with insufficient degree of BP reduction at night. Design and methods. The study included 30 patients (20 men and 10 women, 56±9.3 years, body mass index 30.5±5.3 kg/m2, the duration of arterial hypertension - 7.1±5.8 years), on ineffective dual antihypertensive therapy (BP>140/90 mm Hg). Initially, ambulatory BP monitoring (ABPM) and blood tests were performed. Then, previous therapy was terminated and fixed combination of perindopril 10 mg/indapamide 2.5 mg (Noliprel A Bi-forte) was administered. Patients were randomized into two groups: morning and evening regimens of therapy. After 8 weeks of treatment ABPM and blood tests were repeated. Statistical analysis was done after further separation of patients into groups with sufficient (dippers) and insufficient (non-dippers) degree of BP reduction at night. Results. In the group of "non-dippers" average ambulatory systolic BP (SBP) during wakefulness declined from 149.4±11.7 mm Hg to 129.8±10.6 mmHg (p<0.01), the average ambulatory diastolic BP (DBP) during wakefulness - from 94.7±12.3 mm Hg to 78.3±8.6 mm Hg (ns), ambulatory SBP during sleep - from 146.6±16.1 mm Hg to 121.8±15.7 mm Hg (p<0.01), ambulatory DBP during sleep - from 86.2±9.2 mm Hg to 70.3±6.5 mm Hg (p<0.01). The reduction of nighttime SBP increased from 1.9±5.8% to 6.2±9.3% (p<0.05), the reduction of nighttime DBP from 6.2±3.9% to 9.6±8.2% (ns). ABPM measurements of "non-dipper" sub-groups, who received treatment in the evening or in the morning after 2 months had no significant difference, except the variability of DBP during wakefulness (p<0.05). We didn’t observe statistically significant difference in terms of the nighttime BP reduction. However, nighttime BP reduction was higher in the evening dosing group: SBP - 4.1±11.1% (morning group), 7.8±7.9% (evening group) and DBP - 8.9±11.0 (morning group) and 10.2±5.5 (evening group). Blood tests were in the normal range during the whole study. Conclusion. A fixed combination of perindopril 10 mg/indapamide 2.5 mg (Noliprel A Bi-forte) is effective and safe in patients with both normal and with insufficient degree of reduction in BP at night. Prescription of medication in the evening in non-dipper patients can have the added benefit on the BP profile. Further research is needed.

chronotherapy, arterial hypertension, non-dippers, perindopril, indapamide, fixed combination

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