Fixed-dose Combination Of Perindopril Research Articles

Clinical Effectiveness of the Fixed‐Dose vs Free‐Dose Triple Combinations in Patients with Uncontrolled Arterial Hypertension

Background: The purpose of our study was a comparative assessment of the antihypertensive effectiveness of 2 triple combination antihypertensive therapy (AHT) regimens in a free-dose and fixed-dose combination of perindopril, indapamide, and amlodipine in hypertensive patients with high cardiovascular risk and a poor response to the 2-drug combinations in the clinic practice. Methods and Results: Our study included 143 patients (79 men and 88 women) with arterial hypertension (AH) Grades 1-3 (ESC/ESH, 2018) and high cardiovascular risk who did not achieve the target blood pressure (TBP) on dual combination AHT. The mean age of patients was 55.76±9.35 years; the average duration of AH was 10.69±6.61 years. All patients underwent the examinations according to the 2018 ESC/ESH Guidelines for the management of arterial hypertension. Patients included in the study were divided into 2 groups using the envelope method: Group 1 (n=84) received a fixed-dose, triple combination of perindopril, indapamide, and amlodipine; Group 2 (n=83) received a free-dose combination of these drugs. In both groups, treatment began after discontinuation of previous therapy, with a low dose of a triple combination of antihypertensive drugs (perindopril [5 mg/day], indapamide [1.25 mg/day], amlodipine [5 mg/day]) in the form of a fixed or free combination. The initial doses of perindopril/indapamide/amlodipine in both groups were not statistically different: 6.9±2.4/1.74±0.6/7.1±2.4mg/day in Group 1 and 6.9±2.7/1.95±0.6/7.1±2.5 mg/day in Group 2. After 4 weeks of therapy, if necessary, the doses of drugs were increased, starting with perindopril; the next adjustment of drug doses was carried out after 12 weeks of therapy. The final treatment results were determined after 24 weeks of AHT. Target blood pressure (TBP) of <140/90 mmHg was reached by 94.4% of patients in Group 1 and 83.3% in Group 2 (χ²=7.471, Р=0,006); TBP of <130/80 mmHg was reached by 70% of patients in Group 1 and 42% in Group 2 (χ²=11.61, Р=0,0001). A significant improvement in the diurnal BP profile was also revealed during treatment. According to ABPM data, both groups achieved TBP in terms of the average 24-h and average daytime systolic blood pressure (SBP) and diastolic blood pressure (DBP). Regarding average nighttime SBP and DBP and normalization of average nighttime diastolic blood pressure variability, target values were achieved only in Group 1(P=0.028). In both groups, 24-week triple-combination therapy led to a significant decrease in central SBP, central DBP, and pulse wave velocity (PWV). At the same time, the positive dynamics of central SBP were more pronounced in Group 1 than in Group 2 (Table 4), and PWV in Group 1 reached standard values. Conclusion: The results of our study showed that in the treatment of uncontrolled hypertension on previous therapy in AH patients with high cardiovascular risk, a single-pill triple combination of the ACEI perindopril, the CCB amlodipine, and the thiazide-like diuretic indapamide contributed to the effective daily blood pressure control, the improvement of diurnal blood pressure profile, and a positive effect on central blood pressure and PWV, thereby having a positive impact on the prognosis and quality of life of AH patients with high cardiovascular risk.

Potential of primary drug prevention of cardiotoxicity in the context of anticancer therapy

Aim. To search early signs of cardiotoxicity in patients receiving anticancer therapy and evaluate the effectiveness of cardioprotection with an angiotensin-converting enzyme inhibitor, beta-blocker and myocardial cytoprotector.Material and methods. The study included 98 patients with high and very high risk of cardiotoxicity according to the Mayo Clinic scale (USA). Cancer patients with hypertension were offered cardioprotective treatment with a fixed-dose combination of perindopril and bisoprolol, and patients with very high risk and concomitant coronary artery disease additionally trimetazidine.The patients were divided into 2 following groups: the experimental group (n=50), where patients were prescribed cardioprotective therapy, and the control group (n=48), which consisted of patients who refused or had contraindications to cardioprotection. All patients underwent an examination, including the collection of complaints and anamnesis, physical examination, electrocardiography and echocardiography with an assessment of left ventricular (LV) global longitudinal strain before chemotherapy and 1, 3, 6, 9 and 12 months after initiation of anticancer therapy.Results. In patients of the control group, by the end of the follow-up, the left atrial volume index and LV end-diastolic volume index significantly increased. In the main group, these indicators did not change significantly. In the control group, by the final visit, the LV ejection fraction significantly decreased in comparison with the initial value and the value in the first group. After 6, 9 and 12 months, there was a significant decrease in the LV global longitudinal strain in the control group, while in the main group this indicator remained within the normal range. The mortality rate in the control group was significantly higher (15% vs 2% in the experimental group). In the experimental group, cardiotoxic complications occurred in 28%, while in the control group — in 78% of patients.Conclusion. The study demonstrated the significant importance of cardiac monitoring and primary drug prevention of cardiotoxicity of anticancer therapy. A sig nificant deterioration in LV systolic function was shown in patients with a high and very high risk of cardiotoxicity who did not receive cardioprotective therapy, while its high efficiency was demonstrated in patients of the experimental group.

Клінічна ефективність фіксованої комбінації периндоприлу, індапаміду й амлодипіну у хворих на артеріальну гіпертензію з абдомінальним ожирінням. Результати 12-тижневого спостереження

Актуальність. Лікування артеріальної гіпертензії у хворого з абдомінальним ожирінням є дуже складною задачею. Тому найбільш доцільнім вважається застосування для лікування цієї категорії хворих комбінованої антигіпертензивної терапії з використанням двох і більше компонентів. Метою дослідження було вивчення клінічної ефективності фіксованої комбінації периндоприлу, індапаміду, амлодипіну у хворих на артеріальну гіпертензію в поєднанні з абдомінальним ожирінням. Матеріали і методи. Обстежені 32 хворі на неконтрольовану артеріальну гіпертензію з абдомінальним ожирінням у динаміці 12-тижневої терапії фіксованою трикомпонентною комбінацією — периндоприл/індапамід/амлодипін на тлі застосування аторвастатину і дієтичних рекомендацій. Результати. Показано, що використання фіксованої трикомпонентної комбінації — периндоприл/індапамід/амлодипін на тлі середньодозової статинотерапії і дієтичних рекомендацій у хворих на неконтрольовану артеріальну гіпертензію з абдомінальним ожирінням супроводжується позитивними змінами рівнів ліпідів крові і не викликає погіршення показників вуглеводного і пуринового обмінів. Висновки. Установлена висока ефективність апробованої фіксованої трикомпонентної комбінації антигіпертензивних препаратів у цієї категорії хворих.

Трехкомпонентная комбинированная антигипертензивная терапия у больных артериальной гипертензией с абдоминальным ожирением. Данные 9-месячного наблюдения

Актуальность. Сочетанное течение первичной артериальной гипертензии (АГ) и абдоминального ожирения (АО) характеризуется рефрактерностью к антигипертензивной терапии и значительным повышением сердечно-сосудистого риска. Перспективным подходом к терапии данных больных является раннее применение фиксированных комбинаций антигипертензивных препаратов первой линии. Цель работы состояла в исследовании эффективности фиксированной комбинации периндоприла, индапамида и амлодипина в сравнении с нефиксированной комбинацией указанных препаратов у больных с АГ в сочетании с АО. Материалы и методы. Обследованы 75 больных с АГ II–III степени в сочетании с АО І–ІІ степени (45 мужчин и 30 женщин) в возрасте от 48 до 66 лет. Все больные были разделены на две подгруппы в зависимости от вида антигипертензивной терапии. Первая подгруппа больных (26 пациентов) получала нефиксированную комбинацию периндоприла, индапамида и амлодипина. Вторая подгруппа (29 больных) получала фиксированную комбинацию указанных препаратов. Обследование проводили до начала лечения и через 3, 6 и 9 месяцев. В качестве гиполипидемического препарата все больные получали аторвастатин в суточной дозе 20 мг. Указанная терапия проводилась на фоне рекомендаций по коррекции образа жизни. Результаты. Установлено, что частота достижения целевых уровней артериального давления (АД) у больных, которые получали фиксированную комбинацию препаратов, через 9 месяцев лечения была достоверно выше, чем у больных, которые получали нефиксированную комбинацию. По данным суточного мониторирования АД, фиксированная комбинация назначенных препаратов значительно лучше нормализовала такие параметры, как среднесуточное и среднедневное диастолическое АД (ДАД), средненочное систолическое АД (САД) и ДАД, а также степень ночного снижения и среднесуточную вариабельность САД и ДАД. Апробированная трехкомпонентная фиксированная комбинация давала возможность достичь целевых уровней АД на более низких дозах примененных компонентов, чем нефиксированная комбинация. Выводы. Фиксированная комбинация периндоприла, индапамида и амлодипина в сравнении с нефиксированной у больных АГ в сочетании с АО проявляет достоверно большую антигипертензивную эффективность по данным как офисного измерения АД, так и суточного мониторирования АД на фоне большей приверженности больных к лечению. Для достижения целевых уровней АД у больных АГ в сочетании с АО требуются более низкие дозы компонентов фиксированной комбинации, чем нефиксированной.

Prospects of using genetic testing to increase the effectiveness of antihypertensive therapy

Aim. To compare the effects of 3-month therapy with a fixed-dose combination of an angiotensin-converting enzyme inhibitor (perindopril) and a thiazide-like diuretic (indapamide) in genetically heterogeneous subgroups of patients with hypertension (HTN) for assessing the prospects of using genetic testing for choosing the antihypertensive treatment regimen. Material and methods. Forty-one patients with grade 1-2 HTN with insufficient effectiveness of previous antihypertensive therapy and 20 healthy individuals were examined to compare the prevalence of gene polymorphism in the Rostov Oblast. Patients with HTN underwent standard diagnostic tests, as well as a molecular genetic test to determine the most clinically significant polymorphic genes involved in the pathogenesis of HTN. Results. A relationship was found between the clinical and morphofunctional characteristics of HTN in patients with polymorphisms of AGT, AGTR2, CYP11B2, GNB3, and NOS3 -786 genes, of which 3 polymorphic genes (AGT, AGTR2, CYP11B2) encode the activity of the angiotensin-converting enzyme. The effectiveness of using a combination of renin-angiotensin-aldosterone system inhibitor agent with a thiazide-like diuretic as an initial antihypertensive therapy was evaluated. An analysis showed that fixed-dose combination of perindopril (10,0) and indapamide (2,5) (Noliprel A Bi-forte) in genetically heterogeneous subgroups of HTN patients displays a more pronounced antihypertensive and organ-protective effects in individuals with the mutant allele 704C of AGT T704C polymorphism. A significant decrease in blood pressure was demonstrated according to standard 24-hour monitoring (p<0,05). A significant decrease in the left ventricular mass index (p=0,0001), as well as a significant increase in the ratio of peak mitral flow velocity in early and late diastole (VE/VA) (p=0,0024) were showed. There was a positive effect of therapy on arterial stiffness parameters: a decrease of the pulse wave velocity (p=0,0035), vascular age (p=0,00002) and reflection index (Ri) (p=0,000001), compared with noncarriers of mutant allele 704C of AGT gene. Conclusion. The results obtained indicate the promise of using genetic approaches to develop a personalized drug treatment strategy for HTN patients in order to increase its effectiveness.

Antihypertensive Efficacy of a Triple Fixed-Dose Combination of Perindopril, Indapamide, and Amlodipine: Clinical Effectiveness in Ambulatory Practice (Results of the PETRA Study)

Most patients with arterial hypertension (AH) for successful long-term blood pressure (BP) control require combination of antihypertensive drugs acting on various target organs. Accumulated experience shows that about 30 % of patients require combination therapy with 3 drugs from different pharmacological classes. Efficacy of BP control in real clinical practice with the use of various doses of perindopril, indapamide, and amlodipine as components of taken once-daily triple fixed combination was assessed in the 3-months prospective observational open-label PETRA study. In this study data of office BP measurements and 24-hour ambulatory BP monitoring (ABPM) were obtained from 11209 ambulatory patients (47.6 % women) with AH. Initial mean office BP (BPmoff) was 156.58±16.10 / 91.56±9.33 mm Hg, AH duration - 9.48±7.19 years. After switching to triple fixed dose combination of perindopril, indapamide, and amlodipine BPmoff decreased by 24.81±15.47 / 11.41±9.90 mm Hg (p&lt;0.0001). Doses of perindopril, indapamide, and amlodipine in combination at the final visit were 5 / 1.25 / 5, 10 / 2.5 / 5, and 10 / 2.5 / 10 mg. 24-hour ambulatory BP monitoring (ABPM) was carried out in 76 patients. Mean 24-hour BP lowed from mean 155.51±17.43 / 85.28±11.48 down to 134.63±12.51 / 77.83±8.99 mm Hg (p&lt;0.0001). Clinically relevant improvement of a number of parameters of metabolism occurred after 3 months of the study (in particular, lowering of levels of total and low-density lipoprotein cholesterol [-8.6 and - 11.4 %, respectively], triglycerides [-12,1 %], fasting blood glucose [-6.6 %]). Thus, results of the PETRA study confirmed 24-hour long antihypertensive efficacy of triple fixed dose combination of perindopril, indapamide, and amlodipine. This drug combination can present novel possibility in treatment of patients with AH who have not achieved target BP values on preceding dual combination therapy and fully corresponds with the single pill concept for formation of adherence to therapy.

Efficacy and Tolerability of Fixed-Dose Combination Perindopril/Indapamide in Hypertensive Patients with a History of Stroke or Transient Ischemic Attack: PICASSO Trial

In everyday medical practice, physicians often need to manage patients whose blood pressure is not well controlled. Those with a history of cerebrovascular disease are a high-risk group in need of rapid blood pressure control. The PICASSO study was a real-life, observational trial involving 9257 inadequately treated hypertensive patients who were switched from previous therapy to the fixed-dose combination of perindopril 10mg/indapamide 2.5mg (PI) for 3months. A subanalysis of data of 1117 hypertensive patients who met the clinical criteria of previous stroke or transient ischemic attack was performed. Twenty-four hour ambulatory blood pressure measurements (ABPMs) were also done in a small group of patients (n:38). At baseline, mean systolic/diastolic blood pressure (SBP/DBP) was 161.5 ± 15.2/93.1 ± 9.9mmHg. After 1month with the fixed dose of PI, average office SBP/DBP decreased to 140.0 ± 11.9/83.5 ± 7.7mmHg. After 3months, SBP/DBP had dropped to 132.9 ± 9.8/80.0 ± 6.2mmHg, by 28.6 ± 15.5/13.1 ± 10.0mmHg (p < 0.001). Blood pressure control rate (< 140/90mmHg) was 67.3% after 3months. When data were stratified by baseline blood pressure, decreases in SBP/DBP were statistically significant in patients with all grades (1-3) of hypertension. In patients previously treated with an angiotensin-converting enzyme inhibitor ± hydrochlorothiazide (n = 677), blood pressure decreased by 29.8 ± 15.5/13.3 ± 10.2mmHg (p < 0.001). Decreases in 24-h ABPM values were also significant (n = 38). Treatment was well tolerated; only a few adverse events were recorded. This study suggests that fixed combination perindopril 10mg/indapamide 2.5mg is an effective and well-tolerated treatment for patients with a history of stroke or transient ischemic attack. EGIS Pharmaceuticals Plc.

Terapia złożona w nadciśnieniu tętniczym — połączenie perindoprilu, amlodipiny i indapamidu

Hypertension is one of the epidemiologically most important causes of death in the world. At the same time, its incidence is constantly increasing. Effective control of blood pressure plays a key role in reducing cardiovascular risk and overall mortality. Unfortunately, the majority of Polish patients do not reach the target blood pressure. Improvements in this area can be obtained by using fixed-dose combination drugs. This article, on the basis of the presented clinical case, discusses the benefits of combined antihypertensive therapy, in particular the fixed-dose combination of perindopril with amlodipine and indapamide.

Effect of a fixed-dose combination of perindopril arginine/amlodipine on the level and variability of blood pressure according to its office visit-to-visit measurements and self-measurements at home: A subanalysis of the PREVOSHODSTVO (SUPERIORITY) program

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). 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. 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). 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.

USING A COMBINATION OF PERINDOPRIL, INDAPAMIDE AND ROSUVASTATIN IN THE TREATMENT OF PATIENTS WITH HYPERTENSION AND DYSLIPIDEMIA

Aim . To study the antihypertensive and hypolipidemic effect of a group of drugs including perindopril,rosuvastatin and fixed-dose combination of perindopril and indapamide, in ambulatory patients with hypertension and dyslipidemia. Material and methods . Analysis of the medical data of patients treated with perindopril, indapamide and rosuvastatin in the multicenter, non-interventional study (SYNERGY) was performed. Patients had a diagnosis of hypertension and dyslipidemia, determined in routine clinical practice. Therapy was prescribed to patients in various dosing regimens. The data of anamnesis, physical status, blood pressure measurements, lipid levels were taken from the patient's medical records. The safety assessment was also performed. The duration of follow-up was 8 weeks. Results . A total of 1383 patients were included into the analysis, 53.5% (n=740) of women and 46.5% (n=643) of men. The average age was 55.8 years. 914 patients (66.1%) had previously received antihypertensive therapy, and 439 (31.7%) had previously received lipid-lowering therapy. A significant reduction in the levels of systolic (SBP), diastolic BP (DBP), and low-density lipoprotein cholesterol (LDL-c) was found at the end of the study in all study groups (p<0.05). This demonstrated an adequate antihypertensive and lipid-lowering effect of all treatment regimens. The mean decrease in SBP in treatment groups ranged from 14.3 to 36.2 mm Hg; the mean decrease in DBP – from 3.3 to 22.2 mm Hg. The maximum decrease in SBP was found in the group of perindopril + indapamide + rosuvastatin (PIR) 8 + 2.5 + 20 mg (36.2±12.3 mm Hg); the maximum decrease in DBP – in the group of perindopril + rosuvastatin 8 + 10 mg. The mean decrease in LDL-c level due to the combined treatment with perindopril, indapamide and rosuvastatin ranged from 0.62 mmol/L in PIR groups 2 + 0.625 + 5 mg and 8 + 2.5 + 5 mg to 1.78 mmol/L in PIR group 8 + 2.5 + 20 mg. Three of 1,383 patients reported adverse events after 4 weeks of treatment, while 13 patients – at the end of the study. Conclusion . PIR therapy resulted in a significant reduction in blood pressure in all treatment groups compared with baseline levels. A dose-dependent reduction in SBP and LDL-c levels was found in all treatment groups. The tolerability of all treatment regimens was good.

Оцінка впливу фіксованої комбінації периндоприл + амлодипін на ураження органів-мішеней у пацієнтів з артеріальною гіпертензією (первинні результати дослідження EPHES)

Дослідження EPHES (Evaluation of influence of fixed dose combination Рerindopril/Amlodipine on target organ damage in patients with arterial HypErtension with or without iSchemic heart disease) мало за мету оцінити ефективність фіксованої комбінації периндоприл + амлодипін щодо зниження артеріального тиску (АТ) та динаміки вираженості ураження органів-мішеней у хворих на артеріальну гіпертензію (АГ) з ішемічною хворобою серця (ІХС) та без такої. У первинний аналіз включено дані 30 пацієнтів з АГ без ІХС віком понад 30 років. Рівень систолічного (САТ) і/або діастолічного (ДАТ) АТ у хворих, що до цього не лікувалися, на момент включення мав бути ≥ 160 та/або 100 мм рт.ст., але &lt; 200/120 мм рт.ст.; у тих, хто знаходився на монотерапії або подвійній комбінованій терапії, — ≥ 140/90 мм рт.ст., але &lt; 200/120 мм рт.ст. Усім пацієнтам у день рандомізації призначали фіксовану комбінацію периндоприл + амлодипін у початковій дозі 5/5 мг один раз на добу. При необхідності (АТ &gt; 140/90 мм рт.ст.) дози компонентів фіксованої комбінації збільшували поступово кожні 2 тижні до 10/10 мг, а після 6 тижнів лікування додавали індапамід 1,5 мг, бета-адреноблокатори або альфа-адреноблокатори. Усім пацієнтам проводили: вимірювання маси тіла та зросту, офісних рівнів САТ, ДАТ та частоти серцевих скорочень, добове моніторування АТ, визначення швидкості поширення пульсової хвилі в артеріях еластичного (ШППХе) та м’язового типів, центрального САТ, біохімічне дослідження крові, електрокардіографію, ехокардіографію з Д-графією, вимірювання гомілково-плечового індексу, визначення товщини комплексу інтима-медіа. Тривалість спостереження становила 12 місяців.Лікування за допомогою фіксованої комбінації периндоприл + амлодипін забезпечувало досягнення цільового рівня і САТ, і ДАТ у 60 % випадків на етапі 6 тижнів. Додавання індапаміду 1,5 мг на добу (n = 12) та бісопрололу (n = 1) забезпечило контроль офісного САТ і ДАТ у 100 % пацієнтів на етапі 6 місяців лікування. Зниження офісного АТ супроводжувалося достовірним зменшенням середньодобового, денного та нічного АТ відповідно на 22,3 ± 0,1 мм рт.ст., 19,6 ± 0,4 мм рт.ст., 26,1 ± 0,2 мм рт.ст. та 8,2 ± 0,2 мм рт.ст., 8,4 ± 0,1 мм рт.ст., 7,9 ± 0,1 мм рт.ст. і досягненням цільового середньодобового АТ у 98,7 % пацієнтів. Достовірно зменшилася частка пацієнтів, які характеризувалися як «нон-діппери», з 50 до 23,3 % та варіабельність денних САТ/ДАТ та нічного САТ. Частка пацієнтів із величиною ранкового підйому САТ понад 55 мм рт.ст. достовірно зменшилася з 60 до 20 %. Центральний САТ достовірно знизився з 142,8 ± 2,5 мм рт.ст. до 118,3 ± 2,7 мм рт.ст. (Р &lt; 0,001). Паралельно відбулося достовірне (Р &lt; 0,001) зменшення індексу приросту з 26,8 ± 1,9 % до 11,2 ± 1,7 %. Ефективна щодо зниження АТ терапія протягом року призводила до достовірного регресу ураження органів-мішеней: зменшення гіпертрофії лівого шлуночка (індекс маси міокарда зменшився з 108,8 ± 5,5 г/м2 до 88,3 ± 5,3 г/м2, індекс Корнелла — з 2440,1 ± 67,9 мм • мс до 1987,2 ± 66,8 мм • мс, розмір лівого передсердя — з 41,1 ± 0,2 мм до 38,1 ± 0,3 мм), рівня альбумінурії (з 53,3 ± 5,6 мг/добу до 15,8 ± 3,2 мг/добу), покращенню діастолічної функції лівого шлуночка та пружно-еластичних властивостей аорти (­ШППХе зменшилася з 11,9 ± 0,7 м/с до 9,4 ± 0,8 м/с). Зміни діастолічної функції лівого шлуночка та рівня альбумінурії достовірно та незалежно від змін рівня АТ (і офісного, і центрального) корелювали зі змінами ШППХе та індексу приросту. Проведена антигіпертензивна терапія на основі фіксованої комбінації периндоприл + амлодипін добре переносилася хворими (частота побічних реакцій 6,5 %).

2A.02

The aim of this study was to assess the efficacy of blood pressure (BP) control with fixed-dose combination of perindopril arginine/indapamide (Noliprel) in patients with uncontrolled hypertension.A total of 714 patients with uncontrolled hypertension from the PROTECT (noliPRel - efficacy of blood pressure cOnTrol on nEw diagnosed and unControlled patienTs) database, were included. At the beginning of the study the patients (mean age 64.9 ± 10.5 years; 223 men) were switched from antihypertensive drugs that had proven ineffective in BP control to Noliprel. BP was measured in the third and sixth months of the study. The primary end point was the number of patients reaching target BP levels in the intermediate phases of the study. The SPSS v.17.0 statistical software package was used for data collection and analysis. Results are presented as mean value ± standard deviation. Differences in mean values were analyzed using Student's paired-simple test.Mean systolic BP (SBP)/diastolic BP (DBP) declined significantly from 165.6 ± 14.4/96.8 ± 9.0 mmHg to 132.2 ± 10.7/80.1 ± 6.7 mmHg (p < 0.0001) over the course of the study. SBP/DBP reduction at three month was already -18.7 ± 14.2/-10.0 ± 9.6 mm Hg (p < 0.0001). Patients with BP values at target (<140/90 mmHg) represented 19.8% at 3 months, and 66.8% at 6 months. At the end of study, Noliprel was prescribed in 19.6% (perindopril arginine/indapamide 2.5 mg/0.625 mg), 61.8% (5 mg/1.25 mg), and 18.6% (10 mg/2.5 mg) of cases, respectively. No adverse effects were observed.The fixed-dose combination of perindopril arginine/indapamide was effective and safe in patients with uncontrolled hypertension in reducing BP and maintaining it at target levels.

The effect of combined antihypertensive therapy on left ventricular diastolic function in resting and postexercise patients with arterial hypertension

The correction of left ventricular diastolic function abnormalities hasn’t been well investigated in arterial hypertension.The aim of the study was to determine the effects of two antihypertensive combinations (perindopril/amlodipine and losartan/amlodipine) on the state of diastolic function at rest and after exercise in patients with arterial hypertension.Results. The early diastolic transmitral flow velocity and mitral annular tissue doppler velocities increased under fixed-dose combination of perindopril and amlodipine. The combination shortened the transmitral E-wave deceleration time and isovolumetric left ventricular relaxation time. The prevalence of diastolic dysfunction decreased from 55.8% to 31% on therapy with perindopril and amlodipine (p&lt;0.05). The treatment reduced the frequency of pathologic results of diastolic exercise stress test. These changes were associated with improved exercise tolerance. Therapy with amlodipine and losartan shortened the deceleration time of early diastolic flow at rest and after exercise. The combination of amlodipine and losartan hasn’t reduced the prevalence of left ventricular diastolic dysfunction and hasn’t improved exercise tolerance.Conclusions. The six-month treatment with fixed-dose combination of perindopril and amlodipine has a pronounced effect on improving ofLV diastolic function compared with a combination of losartan and amlodipine.

Randomized evaluation of a novel, fixed-dose combination of perindopril 3.5 mg/amlodipine 2.5 mg as a first-step treatment in hypertension.

To evaluate perindopril 3.5 mg/amlodipine 2.5 mg once daily, a novel fixed-dose combination adapted for first-step treatment in patients with hypertension. This fixed dose had to be equivalent to amlodipine 5 mg in terms of blood pressure efficacy, but with an expected better tolerability profile. We selected two drugs with complementary modes of action, with doses chosen so that each drug would contribute similarly to the overall blood pressure-lowering effect : An international, randomized, double-blind, placebo-controlled study with six equal parallel treatment arms and an 8-week randomized treatment period, whose design, clinical significance and non-inferiority criteria were in accordance with European guidelines. In all, 1581 patients with mild-to-moderate uncomplicated hypertension (mean age 51.7 years) were randomized and 94.7% completed the study. The combination was statistically and clinically superior to placebo (between-group differences: SBP: -7.22 mmHg, DBP: -4.12 mmHg, P < 0.001 for both). Rates of response and normalization of blood pressure were greater with the combination (P < 0.001 for both) and numerical differences relative to placebo were apparent at 2 weeks. The combination was superior to either component given singly (P < 0.001 for both drugs, for SBP and DBP), and was non-inferior to both component drugs given singly at their lowest clinically-approved doses. The components of the combination had similar effects on SBP (perindopril 3.5 mg: -16.3 mmHg; amlodipine 2.5 mg: -16.0 mmHg). Adverse events relating to peripheral oedema were less frequent with the combination than with amlodipine 5 mg. The observed blood pressure-lowering efficacy, rapidity of onset of effect and favourable safety profile of the combination perindopril 3.5 mg/amlodipine 2.5 mg indicate its potential suitability for use as first-step treatment in hypertension.

Влияние фиксированной комбинации периндоприл А/амлодипин на меж- и внутривизитную вариабельность артериального давления и частоты сердечных сокращений в реальной клинической практике в Российской наблюдательной программе КОНСТАНТА

Влияние фиксированной комбинации периндоприл А/амлодипин на меж- и внутривизитную вариабельность артериального давления и частоты сердечных сокращений в реальной клинической практике в Российской наблюдательной программе КОНСТАНТА

Blood pressure and metabolic efficacy of fixed-dose combination of perindopril and indapamide in everyday practice

The aim of the PICASSO study was to evaluate the efficacy and safety of fixed-dose perindopril 10 mg/indapamide 2.5 mg in everyday medical practice. In this 3-month, open-label, observational study, outpatients with primary hypertension who did not reach the blood pressure goal (< 140/90 mmHg) with antihypertensive treatment were enrolled if their treating physician had planned, as part of their ongoing therapy, to switch them to fixed-dose perindopril 10 mg/indapamide 2.5 mg. Blood pressure, heart rate, and metabolic parameters and – optionally – ambulatory blood pressure were measured. Data from 9257 patients were evaluated. Over the course of 3 months, mean blood pressure decreased from 159/93 mmHg to 132/80 mmHg (p < 0.001) and heart rate decreased from 79 to 73 beats/min (p < 0.001). The target blood pressure was reached by 72.7% of patients. Reductions in total cholesterol, low-density lipoprotein-cholesterol (LDL-c), triglycerides, fasting glucose and uric acid levels were clinically significant. Blood levels of high-density lipoprotein-cholesterol (HDL-c), sodium and potassium remained unchanged. Beneficial changes in metabolic parameters were primarily attributed to the reduction in therapy with drugs with unfavourable metabolic profiles (thiazides and beta-blockers). Perindopril/indapamide is an effective and safe antihypertensive treatment in everyday medical practice.

Management of high blood pressure in type 2 diabetes: perindopril/indapamide fixed-dose combination and the ADVANCE trial

Importance of the field: The increase in type 2 diabetes mellitus is associated to cardiovascular morbidity and mortality. This review focuses on the benefits of the fixed-dose combination of perindopril and indapamide on cardiovascular and renal end points in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial.Areas covered in the review: In the last decade, clinical trials have indicated that blood pressure reduction and glucose lowering were effective in reducing morbidity and morbility. The ADVANCE trial has explored both intensive glucose lowering with gliclazide modified release (MR) and intensive blood pressure lowering using a fixed combination of perindopril/indapamide, on top of current treatments, including renin-angiotensin inhibitors.What the reader will gain: In ADVANCE, perindopril/indapamide reduced a composite of macrovascular and microvascular events, also significantly decreasing cardiovascular mortality and death from any cause and reducing coronary and renal complications. The review discusses the relevance of results and the advantages of this therapeutic strategy in clinical practice.Take home message: ADVANCE provides a new, simple and pragmatic treatment algorithm that maximizes clinical benefits and is suitable for all type 2 diabetic patients: intensive blood pressure lowering based on combined perindopril/indapamide with intensive glucose lowering based on gliclazide MR.

OPTIMAL HYPERTENSION MANAGEMENT WITH PRETERAX: S3.1

The 2009 ESH Statement supports the use of fixed-dose combinations for the management of hypertension and the initiation of therapy with combination therapy, particularly in high risk groups. The fixed-dose combination of perindopril and indapamide, widely known as Preterax, combines an ACE inhibitor and a diuretic, two classes that are ideally suited for combination therapy. Preterax acts at many levels – improving tissue perfusion in the microcirculation of the heart and kidneys, while simultaneously combating arterial stiffness in the large conduit arteries. Preterax is effective in lowering blood pressure in patients with uncomplicated essential hypertension (STRATHE study) and is also effective in reversing target organ damage and preventing hard end-points in high risk patients. In the PICXEL study, perindopril-indapamide was superior to enalapril in reversing left ventricular hypertrophy. In the PREMIER Study, in hypertensive subjects with diabetes and albuminuria, the combination of perindopril and indapamide was markedly superior to enalapril in reducing proteinuria. Finally, ADVANCE has demonstrated that Preterax reduces all-cause and cardiovascular mortality, as well as coronary and renal events in patients with type 2 diabetes, regardless of their baseline blood pressure. Recent analyses have confirmed that the effects are consistent across subgroups defined by baseline blood pressure, age, kidney function, cognition, and absolute cardiovascular risk. Preterax is ideally suited to implement the recommendations of the current ESH guidelines for lowering blood pressure across a very wide range of subjects, from those with uncomplicated hypertension, through to those at the highest cardiovascular risk such as those with diabetes or established target organ damage.

Renal protection in diabetic patients: benefits of a first-line combination of perindopril–indapamide (Preterax®)

Type 2 diabetes mellitus (T2DM) is often accompanied by high blood pressure (BP) and the clustering of several cardiovascular risk factors, and is the most frequent cause of end-stage renal disease. The stages of development of overt nephropathy in T2DM patients range from an initial alteration in renal function with an increased GFR, followed by the development of microalbuminuria and macroalbuminuria or proteinuria, featuring an established diabetic nephropathy, which eventually progresses to end-stage renal disease. Early intervention is needed to prevent the development of diabetic nephropathy and requires effective control of the different risk factors, and in particular high BP. In the initial stages of the disease, strict BP control is crucial to prevent the development of initial renal and vascular damage. Adequate BP control is particularly difficult in T2DM patients and in most cases requires the use of combination therapy. Preterax, a fixed-dose combination of perindopril 2 mg and indapamide 0.625 mg, allows BP to be significantly reduced compared with conventional strategies; this combination can be uptitrated to BiPreterax when further BP control is needed. In the PREMIER study performed in T2DM over 12 months, the perindopril/indapamide combination brought about, in addition to excellent BP control, a significant reduction in urinary albumin excretion, compared with monotherapy with enalapril. In more advanced degrees of renal damage, higher doses of the fixed combination have to be considered. The pharmacological basis of the renoprotective effect of perindopril/indapamide is the demonstration that this combination prevented nephropathy as well as proteinuria in obese Zucker rats, independently of BP control. Strict BP control from the initial stages of nephropathy together with inhibition of the renin-angiotensin system is mandatory to prevent albuminuria. The fixed combination of perindopril/indapamide can greatly help clinicians in achieving the above goals, using Preterax in the early and BiPreterax in the late stages of nephropathy.

Fixed-dose combination of perindopril with indapamide in spontaneously hypertensive rats: haemodynamic, biological and structural effects.

The present study was designed to test the effects of chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor (perindopril) and of the diuretic indapamide in spontaneously hypertensive rats (SHR). Adult SHR were treated with placebo or increasing doses of the combination of the drugs (0.3, 1 and 3 mg/kg per day; ratio of doses 0.32). In a separate set of experiments, the effects of the drugs combined (1 mg/kg per day) was compared with those induced by each drug alone. The drug combination dose-dependently decreased systolic blood pressure and its hypotensive effect was more marked than those induced by each treatment administered alone (untreated 208 +/- 5 mmHg, indapamide 185 +/- 5 mmHg, perindopril 150 +/- 3 and the combination 123 +/- 7 mmHg). A 12-week treatment with the drug combination (1 mg/kg per day) was not accompanied by any change in diuresis or urinary excretion of Na or K. The same treatment decreased cardiac hypertrophy and collagen. At the vascular level, the drug combination decreased aortic, carotid and femoral media cross-sectional areas, as well as aortic and carotid collagen density. This latter effect was accompanied by a significant increase in carotid artery compliance assessed in vivo at constant pressure. Finally, in isolated aortae, chronic combined drug treatment was associated with an increased basal release of nitric oxide and a decrease in the hypertension-induced endothelium-dependent contractions in response to acetylcholine. These experiments suggest that chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor and a diuretic such as indapamide may be of value in the treatment of hypertension.