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Aim: To evaluate the efficiency of triple antihypertensive therapy in patients with uncontrolled hypertension and depressive disorders (DD)., Material and Methods: 153 patients with uncontrolled hypertension were examined, of whom 82 patients were diagnosed with mild and moderate DD. A combination of perindopril 10 mg/day, indapamide SR 1.5 mg/day, and amlodipine at an initial dose of 5 mg/day was given to patients with hypertension and DD. After 4 weeks of treatment, if target blood pressure (BP) levels could not be achieved, the dose of amlodipine was increased up to 10 mg/day. General clinical examination and 24-hour BP monitoring (BPM) were performed in all the patients at baseline and in the patients with DD also after 24 weeks of therapy. The traditional measures of the diurnal BP profile, as well as the parameters characterizing arterial stiffness and central aortic pressure (CAP) were estimated., Results: After 8 weeks of therapy, target BP levels were recorded in 63 (76.8%) patients. After 24 weeks of treatment, the hypertensive patients with DD showed significant positive changes in all the investigated 24-hour BPM parameters and normalization of the diurnal BP profile in 65.1% of cases. During the treatment, there were significant decreases in pulse wave velocity, brachial arterial and aortic augmentation indices, aortic systolic and diastolic pressures, and mean aortic BP and an increase in the velocity of the reflected wave., Conclusion: Triple therapy, including perindopril, indapamide SR, and amlodipine, contributed to the achievement of target BP levels in the majority of hypertensive patients with DD, with significant positive changes in all 24-hour BPM parameters, optimization of the diurnal BP profile in most patients, clinically significant improvement of the parameters that characterize arterial stiffness and CAP.

Aim: To study the effect of a fixed-dose combination of perindopril arginine/amlodipine (prestans) on the goal levels and variability of blood pressure (BP) according to its office visit-to-visit measurements and self-measurement (OVVM and SM) in a subgroup of 483 people from the population of the Russian observational SUPERIORITY program, most cases of whom are given the combination replacing the previously ineffective mono- and combination antihypertensive therapy (AHT)., Subjects and Methods: The subanalysis included data on 483 patients (34% men) aged 57.9±10.8 years with uncontrolled hypertension, who were both untreated and treated with antihypertensive mono- or combination therapy using a free or fixed-dose combination of 2-3 antihypertensive drugs and in whom the physicians decided to use prestans to correct AHT. The follow-up period was 24 weeks., Results: At the end of the investigation, the patients received prestans in the following doses: 5/5 mg (34% of the patients), 10/5 mg (39.5%), 5/10 mg (3.9%), and 10/10 mg (22%). In the analyzed patient group, the baseline BP was 160.8±8.8/92.6±7.4 mm Hg and dropped to 125.9±7.9/77.8±5.0 mm Hg at 24 weeks (p<0.001). According to SM, the morning BP significantly decreased from 147.0±13.3/85.6±7.2 to 127.5±8.3/78,9±5.6 mm Hg at 24 weeks (p<0.001). The evening BP readings showed the similar trends. Target BP was achieved in 93 and 78% of the patients, as shown by OVVM and SM, respectively. According to SCM, the day-to-day variability of BP significantly decreased from 5.1±3.2/3.4±2.3 Hg mm at Visit 2 to 2.7±2/0/2,3±1/5 mm Hg at Visit 5 (p<0.001)., Conclusion: The use of the fixed-dose combination of perindopril arginine/amlodipine in hypertensive patients just at the beginning of treatment, by switching from insufficiently effective mono- or combination AHT to the fixed-dose combination of perindopril arginine/amlodipine, is an effective way to optimize AHT in clinical practice, which lowers the BP level and variability, as evidenced by both OVVM and SM.

Aim: To provide a detailed analysis of the efficacy and tolerability of Prestance (perindopril A/amlodipine) in a subgroup of 1936 people participating in the Russian observational CONSTANTA program, most cases of whom were given the drug as a substitute for earlier ineffective monotherapy and combination therapy, without using other antihyperterisive agents., Subjects and Methods: The analysis included 1936 patients (aged 58.2±7.5 years; 35% men) with uncontrolled hypertension who received angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (AT II) receptor antagonists alone or in conjunction with free or fixed-dose combinations of two-three antihypertensive agents and who were given Prestance to correct antihypertensive therapy, as decided by their doctors. The goal blood pressure (BP) was <140/<90 mm Hg for all the patients. Their treatment lasted three months., Results: At the end of trial, the patients received Prestance (perindopril A/amlodipine) in the following doses: 5/5 mg (15% of the patients), 10/5 mg (39.9%), 5/10 mg (9.8%), 10/10 mg (36.6%). In the analyzed group, the baseline BP was 163.4±13.7/94.6+10,1 mm Hg; heart rate (HR), 74.0±10.9 beats/min; 3 months later, there were decreases in BP to 130.8±10.2/78.5±7.2 mm Hg (as compared to the baseline values; p<0.001) and in HR to 67.9?5.4 beats/min (p<0.01). The mean BP reduction was 32.6±10.8/16.1±7.2 mm Hg. A total of 1607 (83.0%) patients achieved the goal BP while 1520 (78.5%) patients did this without having another antihypertensive therapy., Conclusion: To switch hypertensive patients receiving ineffective monotherapy or dual therapy using ACE inhibitors or AT II receptor blockers to fixed-dose perindopril A and amlodipine combination (Prestance) is a rational way of optimizing a therapy regimen in these patients with a wide range of baseline BP levels; moreover, four out of five patients did not need any additional antihypertensive drug.

Aim: To estimate changes in treatment adherence and motivation and quality of life in Prestance-treated population of the observational CONSTANTA program., Subjects and Methods: The effect of Prestance on treatment adherence and motivation and quality of life was evaluated in 2435 participants of the CONSTANTA program. It included patients with uncontrolled hypertension who generally received angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists alone or in conjunction with free or fixed-dose combinations of 2-3 antihypertensive agents and who were additionally given Prestance to correct antihypertensive therapy, as decided by their doctors. The goal blood pressure (BP) was less than <140/90 mm Hg for all the patients. A modified Morisky- Green questionnaire was used to measure adherence, motivation, and awareness in the patients. Their treatment lasted three months., Results: A total of 1992 (81.8%) patients in the analyzed group achieved the goal BP. When included in the study, 1076 (44.2%) patients were defined as adherent to therapy; the mean adherence index was equal to 3.12 ± 0.86 scores; at 3 months of therapy, the number of adherents increased up to 1997 (82%) and the mean adherence index rose up to 3.6 ± 0.74 scores. With high baseline motivation, its mean score was 1.25 ± 0.79 in 40.1% of the patients; at 3 months the number of the motivated rose up to 70.9% (p < 0.05) and the mean score was as high as 1.75 ± 0.60 (p < 0/05). At baseline, 44.2% of the patients showed a high awareness; its mean score was 1.42 ± 1.12; at 3 months of therapy, both indicators significantly increased up to 82% (p < 0.05) and 2.38 ± 0.80, respectively., Conclusion: The well tolerable BP lowering during Prestance therapy is attended by a substantial rise in treatment adherence and motivations in the patients even in the absence of special purposeful measures.

The paper describes a clinical case of the efficacy of a fixed-dose combination of perindopril and amlodipine used in a hypertensive patient. It shows its clinical effectiveness with no impact on blood lipid and glucose levels. 24-hour blood pressure monitoring revealed a reduction in daily blood pressure, including its variability, in pulse wave propagation velocity and central aortic pressure.

Aim: To investigate the effects of ivabradine in combination with perindopril on cerebral blood flow and endothelial functional activity., Subjects and Methods: Sixty-four patients with coronary heart disease (CHD) and arterial hypertension (AH) were examined. Group 1 (n = 38) patients took ivabradine in combination with perindopril and Group 2 (n = 26) received metoprolol. At baseline and 8 weeks after therapy, 24-hour blood pressure (BP) monitoring and electrocardiography were done, cerebral blood flow was estimated by Doppler ultrasound, reactive hyperemia and nitroglycerin tests were performed, and plasma nitrite levels were determined., Results: With a comparable decrease in BP and heart rate in the internal carotid artery basin in both groups over time, there was a fall in peak systolic blood flow velocity; Group 1 showed a reduction in pulsatility index (PI) and systolic/diastolic ratio (ISP). After 8 weeks, there was an increase in endothelium-independent vasodilation and baseline blood flow velocity in the brachial artery in Group 1 and a rise in endothelium-dependent vasodilation in Group 2; in both groups, reactive hyperemia were higher in the brachial artery basin. No changes in nitrite levels were recorded during therapy. There was an inverse correlation between PG and PI in Group 1 and between PG and ISP in Group 2., Conclusion: By unidirectionally affecting the vasomotor function of the endothelium, ivabradine in combination with perindopril versus metoprolol has a more favorable effect on circulatory resistance and blood flow velocity in the brachiocephalic arteries of patients with CHD and AH.

This review provides an analysis of the results of Russian and foreign clinical trials that have shown a high antihypertensive efficacy and tolerability of combined medications containing fixed doses of perindopril and indapamide.

Aim: To estimate the time course of changes in brachial artery (BA) functional parameters in patients with unstable angina (UA) treated with angiotensin-converting enzyme inhibitors., Subjects and Methods: After examination, 30 patients with Braunwald Classes IB and IIB UA were randomized to two groups to receive perindopril or enalapril as part of combination therapy (Group 1 and Group 2, respectively). The authors carried out BA duplex scanning with a reactive hyperemia test, calculated the values of its viscoelastic properties, and determined pulse wave velocity (PWV) at baseline and after 3 months., Results: The patients of both groups did not differ in BA functional parameters at baseline. Following 3 months, Group 1 showed a reduction in Young's (p = 0.046) and Peterson's (p = 0.049) modules, an increase in compliance (p = 0.016) and distensibility (p = 0.02) coefficients, and a decrease in PWV (p = 0.23). Estimation of endothelium-dependent vasodilation of BA revealed a significant increase in its diameter increment both at testing minutes 1 (p = 0.047) and 2 (p = 0.049). In Group 2, only did the distensibility coefficient change significantly (p = 0.041). After the reactive hyperemia test, there was a significant rise in BA diameter increment at minute 1 (p = 0.047) and no change in this indicator at minute 2., Conclusion: After 3-month treatment, the viscoelastic properties of BA improved in all indicators in the patients taking perindopril as part of combination therapy. The use of enalapril improved only an arterial distensibility index. The BA endothelial function estimated by its diameter increment also displayed better changes in the patients receiving perindopril.

Aim: To study ways of realization of pleiotropic effects of treatment with low-dose combination of perindopril arginine with indapamide in hypertensive patients with metabolic syndrome (MS)., Material and Methods: Thirty hypertensive patients with MS received low-dose combined drug noliprel A (Servier, France). In weak hypotensive effect noliprel A forte was used. An antihypertensive (by the data of 24-h blood pressure monitoring), sympatholytic (by the levels of ACTH and cortisol in blood plasma, by variability of the heart rate)and metabolic effects of the drug were assessed after 3 weeks, 3 and 6 months of treatment. Carbohydrate metabolism was studied by glucose and insulin blood levels before meal and after it. Lipid and purin metabolism were assessed by enzyme method, leptin levels - by enzyme immunoassay., Results: 24-h blood pressure monitoring registered a stable regular blood pressure lowering, target blood pressure was achieved in 78.6% patients. Blood ACTH concentration significantly reduced showing a sympatholytic action of the drug. Parameters of lipid, carbohydrate and purin metabolism changed insignificantly. Positive changes were seen in anthropometric indices, leptin tended to decrease. Changes in these parameters, sympatholytic and hypotensive effects depended on plasmic levels of leptin., Conclusion: A fixed low-dose combination of perindopril arginine with indapamide in a stable hypotensive effect and metabolic neutrality influences some key components of MS including hyperactivity of sympathic autonomic nervous system component and hyperleptinemia.

Aim: To study endothelial function and vascular elasticity in hypertensive patients with coronary heart disease (CHD) and approaches to correction of the impairments with felodipin and perindopril., Material and Methods: The trial included 34 hypertensive patients with CHD and 17 controls free of cardiovascular diseases. The above cardiovascular patients were randomized into two groups: 15 patients of group 1 received felodipin, 19 patients of group 2 were given perindopril. If the target blood pressure was not achieved after 4 weeks of treatment, 12.5 mg hydrochlorotiazide was added. 24-h monitoring of blood pressure, reactive hyperemia and nitroglycerin tests were made initially and after 8-week treatment. Also, calculations were made of pulse wave velocity (PWV) on the carotid-femoral and carotid-radial segments (Ve and Vm), of elastic modulus for arteries of the elastic and muscular types (Ee and Em)., Results: Baseline endothelium-dependent and non-endothelium-dependent vasodilations (EDVD and NEDVD) in cardiovascular patients were lower than in the controls while Ve and Ee were higher. Systolic blood pressure (SBP), pulse blood pressure (PBP), stress SBP and EDVD correlated. The treatment led to reduction of mean circadian, diurnal and nocturnal SBP, diastolic blood pressure (DBP), PBP, Ve and Ee, to elevation of EDVD., Conclusion: EDVD in hypertensive patients with CHD is related with SBP and PBP. Felopidin had both an antihypertensive and vasoprotective effects due to improved endothelial function and better elasticity of the major arteries comparable to effects of perindopril.

Aim: To assess clinical efficacy of mineral water and perindopril in convalescents after hemorrhagic fever with renal syndrome (HFRS) in outpatient setting., Material and Methods: The study covered 113 HFRS convalescents. HFRS was confirmed serologically. The patients were divided into three groups: group 1 (n = 50) received no rehabilitation care; group 2 (n = 32) drank mineral water "varzi-yatchi"; group 3 (n = 31) drank mineral water and took perindopril (2 mg/day). After-treatment continued for 30-35 days. The effect was assessed by a complex of clinical-laboratory and functional tests for examination of renal functions (Reberg-Tareev, Zimnitsky tests, estimation of uric acid clearance and renal functional reserve, an 18-hour water deprivation test)., Results: Mineral water varzi-yatchi and perindopril had a favourable effect on clinical condition and renal functions of HFRS convalescents. Compared to the controls (p < 0.05), they had less severe weakness, lumbar pains, edema of the lower limbs; positive changes in intraglomerular hemodynamics, renal transport of beta 2-microglobulin (MG), uric acid transport., Conclusion: It is shown that HFRS convalescents have defective glomerular and tubulointerstitial systems of the kidneys. These disorders demand a differential therapeutic approach. Drinking mineral water improves some tubular functions. The addition of perindopril is necessary in detection of arterial hypertension, impairment of intraglomerular hemodynamics, hyperexcretion of beta 2-MG, osmoregulating renal dysfunction.

Aim: To investigate effects of trimetazidine and perindopril on myocardial function and metabolism in patients with cardiac failure after myocardial infarction., Material and Methods: A comparative study was mode of the effects of 6-month therapy with perindopril, trimetazidine alone and in combination on clinical symptoms, left ventricular function and perfusion, glucose utilization, excretion and utilization of fatty acids in the zones of postinfarction scar, periinfarction ischemia and in without infarction changes., Results: Combined treatment with the ACE inhibitor and trimetazidine produced positive clinical and functional-metabolic shifts in postmyocardial infarction patients with cardiac failure., Conclusion: The addition to the program of mild cardiac failure treatment early after myocardial infarction of an ACE inhibitor and a cytoprotective drug (trimetazidine) promotes more complete clinical compensation of the patients.

Aim: To study efficiency and safety of application of perindopril (prestarium) in patients with chronic cor pulmonale (CCP)., Material and Methods: The trial included 26 patients with chronic obstructive pulmonary disease complicated with CCP and cardiac failure of NYHA class II-III. The study group of 16 patients received perindopril 2-4 mg/day for 3 months. 10 controls received routine therapy. All the patients were examined before the treatment and 3 months after it using physical examination, echocardiography, Doppler echocardiography, 24-h Holter ECG monitoring, assessment of potassium and creatinine in the serum, quality of life., Results: The treatment decreased functional class of cardiac failure and mean pulmonary arterial pressure, lowered malignant arrhythmia frequency, improved quality of life and intracardiac hemodynamics, inhibited right ventricular remodelling., Conclusion: Perindopril is well tolerated and safe efficient medicine in patients with decompensated CCP.