scholarly journals Resistant arterial hypertension: problems and opportunities for personalised drug therapy

2020 ◽  
Vol 27 (5) ◽  
pp. 60-73
Author(s):  
A. V. Fendrikova ◽  
V. V. Skibitskiy ◽  
E. S. Garkusha ◽  
A. I. Chesnikova ◽  
M. Е. Statsenko

Background. Effective drug therapy for resistant arterial hypertension is among major problems in modern medicine. The actual prevalence of resistant arterial hypertension is unknown, and its pathogenetic mechanisms are actively investigated. Among its important components is salt-sensitivity of the patient. At the same time, effi cacy of combined antihypertensive therapy in relation to salt-sensitivity of patients with resistant arterial hypertension is not fully understood.Objectives. Effi cacy assessment of personalised drug therapy in salt-sensitive and salt-resistant patients with resistant arterial hypertension.Мethods. We conducted a non-randomised controlled study with the observation time of 48 weeks. All patients had ambulatory blood pressure monitoring (ABPM) in the onset and past 48 weeks of treatment. Prior to therapy, the patient’s salt-sensitivity was determined with ABPM in salt loading (V.I. Kharchenko’s test). Two cohorts were formed with respect to the test results to include salt-sensitive (n = 67) and salt-resistant (n = 54) patients. Both cohorts received a combined therapy: enalapril 10 mg twice a day, amlodipine 10 mg/day, hydrochlorothiazide 12.5 mg/day, aliskiren 150 mg/day. If a target blood pressure was not observed in 3 weeks, aliskiren was elevated to 300 mg/day. Therapeutic effi cacy was assessed with ABPM after 48 weeks. Non-parametric statistical analysis was performed using Statistica 6.10 (StatSoftInc, USA).Results. The study included 121 patients with resistant arterial hypertension, median age 63 [58;67]. With background therapy, the target blood pressure was observed in 29 (43.4%) patients in cohort 1 and in 38 (70.4%) — in cohort 2 (intergroup p < 0.05). Statistically signifi cant lower ABPM values were registered in both cohorts after 48 weeks. Daily blood pressure normalised with therapy in 62.1% of patients in cohort 1 and in 68.4% — in cohort 2. The salt-resistant cohort exhibited a more pronounced reduction in ABPM values compared to salt-sensitive patients.Conclusion. Salt-sensitivity is a factor for personalising antihypertensive drug therapy in patients with resistant arterial hypertension due to specifi city of mechanisms for maintaining high blood pressure. Combined antihypertensive therapy with aliskiren is statistically more effective in salt-resistant than in salt-sensitive patients.

2018 ◽  
Vol 90 (12) ◽  
pp. 28-33 ◽  
Author(s):  
E M Elfimova ◽  
A Yu Litvin ◽  
I E Chazova

Aim. To study the effectiveness of a fixed combination of perindopril and amlodipine, with the subsequent addition of indapamide-retard in male patients with arterial hypertension (AH), obesity and severe sleep apnea (OSAS). Materials and methods. The study included 43 male patients in whom antihypertensive therapy titration was performed to achieve target blood pressure values with a fixed combination of calcium antagonist amlodipine (10 mg) and an angiotensin-converting inhibitor perindopril (5-10 mg) and indapamide-retard. At baseline and after 4-6 weeks, the effectiveness of antihypertensive therapy was monitored according to clinical measurements and ambulatory blood pressure monitoring (ABPM). An assessment of the carotid-femoral pulse wave velocity (cfPWV), aortic PWV (aoPWV), and ankle-brachial PWV (abPWV) was performed. Results and discussion. Target blood pressure values (according to clinical blood pressure, 24-hour blood pressure monitoring) during therapy with amlodipine 10 mg and perindopril 10 mg reached 65% of patients and another 30% reached target blood pressure when adding indapamide-retard 1.5 mg, that is - 95% of all patients included in the study. Upon reaching the target blood pressure values, a significant decrease in cfPWV, aoPWV and abPWV was observed. Conclusion. The fixed combination of perindopril arginine and amplodipine, with the addition of indapamide retard in male patients with hypertension 1st degree in the presence of obesity and severe OSAS allows to reach effective control of blood pressure and improve the elastic properties of large arteries, which can lead to a favorable organoprotective effect in this category of patients.


Author(s):  
S. V. Nedogoda ◽  
A. V. Sabanov

Aim. To evaluate the features of pharmacotherapy in achieving different levels of target blood pressure (BP) in patients with arterial hypertension (AH) with the absence or presence of comorbid diseases in real outpatient practice.Material and methods. At the open multicenter observational study, outpatient physicians filled original patient questionnaires, which reflected the demographic data of patients, the presence of comorbid diseases and conditions prescribed antihypertensive drugs and achieved during treatment with their use levels of systolic (SBP) and diastolic (DBP) blood pressure (BP), body mass index (BMI), creatinine and blood glucose levels, as well as information about smoking. The obtained data were stratified into groups depending by the level of blood pressure achieved in patients during the therapy, as well as depending on the existing comorbid diseases. Estimated rate of prescription of antihypertensive agents, the number of components of therapy, the number assigned to tableted dosage forms (tablets). We also evaluated the frequency assignments of fixed combinations (FC). Results. The study included data from 2073 patients. They were divided into six groups according to the level of BP achieved. The groups were comparable by demographic and anthropometric characteristics, as well as in gender representation. In patients of the first group on the background of therapy were achieved the lowest values of blood pressure — 120­129/<80 mm Hg. art. They were less likely than other groups to detect comorbid diseases, less frequently prescribed thiazide/thiazide­like diuretics (TD), and FC were prescribed in 33,8%. In patients of the second group the blood pressure level was 130­139/<80 mm Hg. art., the duration of hypertension was the smallest, they were most often prescribed angiotensin II receptor blockers (ARBS) and so on, and the share of FC was the maximum among the compared groups — 42,3%. In the third group, the blood pressure level was 120­139/80­89 mm Hg. St. These patients are most often prescribed angiotensin converting enzyme inhibitors (ACEi), but rarely angiotensin receptors blockers (ARB), frequency assignments of FC — 37,8%. The level of blood pressure in patients of the fourth group who did not achieved the target value of SBP (≥140 mm Hg), in the fifth group — the target value of DBP (>90 mm Hg), and in the sixth group — the target values of SBP (≥140/>90 mm Hg. art.). Their share in the total sample was 19,9%, 4,1%, and 41,2%, respectively. Patients from these groups were more likely to have comorbid diseases, they were more often prescribed four or more components of therapy. BP level <130/<80 mm Hg in patients with type 2 diabetes mellitus (DM 2) was achieved in 4,2%, in patients with coronary heart disease (CHD) in 8,3%. In these groups, a high frequency of beta­blockers (BB) was noted. Patients with chronic kidney disease (CKD) had blood pressure levels of 130139/<80 mm Hg was 7,9%. Among patients with stroke/transient ischemic attack (TIA) blood pressure 120­129/<80 mm Hg was achieved in 2%. In the general sample of patients, one component of antihypertensive therapy was prescribed in 5,8%, two — in 48,3%, three — in 34,7%, four or more — in 11,2%.Conclusion. Target blood pressure <140/90 mm Hg was achieved at 34,8%, and the level of blood pressure <130/80 mm Hg — only at 11,5% of patients. In these patients, comorbid diseases were less often observed, from hypotensive drugs, ACEI, BB or TD were most often used, the predominant appointment of twocomponent antihypertensive therapy was noted, which was most often presented in the form of two tablets. In patients with comorbid diseases revealed a very low proportion of achieving the target level of blood pressure: with DM 2 — 4,2%, with CKD — 7,9%, with IHD — 8,3%, with stroke/TIA — 2%. Among the patients of the whole sample, two­ and three­component antihypertensive therapy was most often prescribed (48,3% and 34,7%, respectively). A greater number of antihypertensive components were prescribed to patients with several comorbid diseases, and, consequently, with a more severe course of hypertension. 


2019 ◽  
Vol 23 (1) ◽  
pp. 37-44 ◽  
Author(s):  
O. B. Kuzmin ◽  
V. V. Zhezha ◽  
L. N. Landar ◽  
O. A. Salova

Arterial hypertension (AH) resistant to drug therapy is the phenotype of uncontrolled AH, in which patients receiving at least 3 antihypertensive drugs, including a diuretic, maintain blood pressure above the target level. Initially, the term refractory hypertension was also used to refer to resistant hypertension. Recently, however, refractory hypertension has been isolated into a separate phenotype of difficult to treat hypertension, which is defined as insufficient control of target blood pressure, despite the use of at least 5 different mechanisms of antihypertensive drugs, including long-acting diuretic and antagonist of mineralcorticoid receptors. Resistant hypertension is detected in 10–15 % of all hypertensive patients receiving drug therapy, and is often found in patients with chronic kidney disease. Hypertension can be a cause and/or consequence of kidney damage and is typical of most patients with chronic kidney disease. The lack of control of target blood pressure in a significant proportion of hypertensive patients with CKD who receive at least 3 antihypertensive drugs of different mechanisms of action indicates a lack of effectiveness of antihypertensive therapy, which not only accelerates the loss of renal function, but also significantly worsens the prognosis, contributing to such people risk of cardiovascular and renal complications. The review presents data on the prevalence, prognostic value of resistant hypertension in patients with chronic kidney disease, features of its formation and approaches to increasing the effectiveness of antihypertensive therapy in this patient population.


2019 ◽  
Vol 15 (4) ◽  
pp. 502-509
Author(s):  
N. B. Perepech ◽  
V. D. Shurygina ◽  
A. V. Tregubov

Aim. Examination of knowledge of the basic provisions of clinical guidelines for the management of patients with arterial hypertension and finding out the readiness of doctors for the practical application of updated recommendationsMaterial and methods. Anonymous questionnaires of 306 doctors served as material for the study. The questionnaire consisted of two parts. The introductory part included questions that allow to find out the specialty, work experience, gender, age, and whether the respondent has cardiovascular risk factors. The main part of the questionnaire included 16 questions regarding provisions of the guidelines on the diagnosis and treatment of arterial hypertension in force at the time of the survey (2017/2018 academic year). Statistical processing of the results was carried out using the Microsoft Excel 2010 software package. Differences were regarded as significant at p<0.05.Results. The findings suggest that both therapists and cardiologists do not give due importance to the risk stratification of cardiovascular complications in patients with arterial hypertension and are not sufficiently aware of the possibilities and limitations of the use of combinations of antihypertensive drugs. Therapists worse than cardiologists know the main points of the clinical guidelines for the management of patients with arterial hypertension (target blood pressure levels during treatment [64.6% vs 87.7%, p<0.001], indications for combination antihypertensive therapy starting, the possibility of fixed dose combinations using [52.3% vs 83.9%, p<0.001]). A significant part of physicians (both cardiologists and therapists) adequately assess the antihypertensive treatment effectiveness, not enough frequent achievement of the target blood pressure level in their patients and is willing to provide more strict control of blood pressure.Conclusion. The results of the survey indicate the need of the active education of doctors in the management of patients with arterial hypertension. The most attention should be paid to the training of therapists and general practitioners on the cardiovascular complications risk stratification, the using of the antihypertensive drugs combinations use and methods to increase patient adherence to antihypertensive therapy.


2022 ◽  
Vol 7 (4) ◽  
pp. 62-69
Author(s):  
V. A. Tsvetkov ◽  
E. S. Krutikov ◽  
S. I. Chistyakova

Aim of the study: to develop personalized approaches to combined antihypertensive therapy in patients with type 2 diabetes mellitus and arterial hypertension, depending on the parameters of the daily blood pressure profile and heart rate variability.Material and methods. We examined 322 patients with type 2 diabetes and arterial hypertension who had not previously received antihypertensive drugs on a regular basis. At the first stage, patients were prescribed Perindopril 10 mg per day and Indapamide retard 1,5 mg per day. In the absence of reaching target blood pressure (BP) levels after 28 days, a third antihypertensive drug was added — Amlodipine 5 mg per day, followed by titration to 10 mg 1 r per day (group I) or a b-blocker — Carvedilol at a dose of 12,5 mg 2 r per day, also followed by titration up to 25 mg 2 r per day (group II). Daily monitoring of BP and ECG was carried out, the average daily heart rate (HR), circadian index (CI), as well as heart rate variability were determined.Results and its discussion. Patients with type 2 diabetes have a high variability of blood pressure throughout the day, high pulse blood pressure, as well as a rigid circadian profile of heart rate. The appointment of a standard two-component antihypertensive therapy, including Perindopril 10 mg and Indapamide retard 1,5 mg per day, allows reaching the target blood pressure only in 46% of patients. The addition of amlodipine or carvedilol significantly increases the effectiveness of therapy, allowing more than 80% of patients to achieve the target blood pressure. At the same time, the use of amlodipine leads to a greater extent to a decrease in pulse pressure, and the inclusion of carvedilol improves the circadian profile of blood pressure and heart rate, and has a positive effect on heart rate variability.


2016 ◽  
Vol 13 (4) ◽  
pp. 36-40
Author(s):  
E M Elfimova ◽  
A R Zairova ◽  
M V Andrievskaya ◽  
R M Bogieva ◽  
A N Rogoza ◽  
...  

Goal: to study the effectiveness of combination antihypertensive therapy (AHT) and its influence on the indices characterizing the arterial stiffness of various types in patients with arterial hypertension (AH) in combination with obesity and severe obstructive sleep apnea (OSA). Material and methods. The study included 27 male patients with hypertension [143.0 (142.0; 150.0)/91.0 (85.3; 94.8) mm Hg. century], obesity [body mass index of 33.8 (32.0; 37.2) kg/m2] and OSA was severe [the index of apnea/hypopnea - AHI - 46.8 (33.3; 63.4) events per hour] who underwent AHT titration to achieve target values of blood pressure (BP), a fixed combination of the calcium antagonist amlodipine (10 mg) and the angiotensin-converting enzyme inhibitor perindopril (5-10 mg). At baseline and after 4-6 weeks when reaching target blood pressure was assessed pulse wave velocity (PWV) using different instrumental techniques. Carotid-femoral PWV (CFSP) was determined by applanation tonometry (SphygmoСor AtCor, Australia), aortic PWV - ultrasonic technique in the descending aorta (thoracic spine), the ankle-brachial PWV - using volumetric sphygmography (VaseraVS-1000 Fukuda Dens, Japan). Results. The target pressure (according to clinical blood pressure, daily monitoring blood pressure) on the background of amlodipine 10 mg and perindopril 5 mg was 58% patients and 42% of patients reached the target level of blood pressure against the background amlodipine 10 mg and perindopril 10 mg. On a background of 4-6 weeks of admission AHT 33.8% increase in the number of patients with a normal circadian profile of blood pressure - «dipper». Upon reaching the target blood pressure revealed a significant decrease CFSP, ankle-brachial PWV and aortic PWV 11.4, 11.0 and 15.4%, respectively. Conclusion. A fixed combination of perindopril arginine and amlodipine in patients with arterial hypertension of the 1st degree in the presence of obesity and OSA allows achieving a good level of BP control, to improve the performance of the daily profile and to improve the elastic properties of large arteries, which has a beneficial protective effect in these patients.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Sindt ◽  
T Madej ◽  
S Grimm ◽  
M Knaut

Abstract Objectives First generation baroreflex activation therapy (BAT) devices showed clinical efficacy in patients with drug-resistant arterial hypertension (AHT), but the safety profile was insufficient. Data regarding efficacy of second-generation devices were generated mostly from office blood pressure (BP) measurements or short-term 24-hour ambulatory blood pressure measurements (ABPM). We present a mid-term prospective registry to evaluate the efficacy and safety of recent BAT devices. Purpose The purpose of our study was to find a method that helps patients with drug-resistant arterial hypertension to control their blood pressure. Further we sought to reduce the overall amount of antihypertensive drugs to lessen side effects, as well as the effects of polypharmacy. Methods All patients receiving Barostim neo between November 2013 and June 2019 for resistant AHT were prospectively included into this observational study. ABPM was performed at baseline, in 3-month intervals in the first year after BAT implantation and in 6-month intervals afterwards for up to 42 months. Patients were assigned into two groups of responders and non-responders. Non-responders had a mean blood pressure drop (BPD) below 5mmHg. Responders in turn were categorized into 3 sub-groups (low-BPD between 5–9 mmHg, medium-BPD between 10–19 mmHg and high-BPD ≥20 mmHg). The primary efficacy end-points were changes in systolic and diastolic BP and number of antihypertensive medications. The primary safety end point was BAT-related major adverse events (MAE). Results 64 patients (mean age 63 years, 67% males) were included. Only patients who completed a 24-hour ABPM during a follow up were counted in the statistical analysis. We had an overall responder rate of 67.8%. Out of those 15.4% had low-BPD, 38.4% medium-BPD and 46.2% had a high-BPD. Systolic BP decreased over the 3.5-years period from 168±17 mmHg to 149±19 mmHg (n=19, mean change −18.8 mmHg; 95% confidence interval [CI]: −29.32 to −8.36; p&lt;0.0007). Diastolic BP decreased from 97±16 to 85±12 mmHg (n=19, mean change −11.7 mmHg; 95% CI: −19.2 to −4.2; p&lt;0.0021). The mean number of antihypertensive drugs was reduced from 6.9±1.3 to 5.2±1.5 (n=19, mean change −1.7; 95% CI: −0.8 to −0.27; p&lt;0.0009). The time course of primary end-points is shown in Fig.1. Freedom from BAT-related MAE was 93.5%. 4 perioperative complications (1 pocket bleeding, 1 pocket infection, 1 N. hypoglossus palsy, 1 hoarseness) resolved without residual side effects. There were five non BAT related deaths (7,8%) in the follow up period. Conclusion Systolic and diastolic ABP, as well as number and dosage of antihypertensive drugs decreased significantly during 3.5-years follow-up after Barostim neo implantation in 64 consecutive patients (of whom 62 completed at least one follow-up). No MAE associated with BAT were observed after the perioperative period. However, further controlled trials are needed to confirm the long-term efficacy of BAT. Figure 1. Mean blood pressure drop Funding Acknowledgement Type of funding source: None


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