Achieve Target Blood Pressure Levels Research Articles

Efficiency of triple antihypertensive therapy in patients with uncontrolled hypertension and depressive disorders

To evaluate the efficiency of triple antihypertensive therapy in patients with uncontrolled hypertension and depressive disorders (DD). 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. 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. 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.

Arterial hypertension treatment changes in Yaroslavl region: results obtained after 4 years of complex program of regional healthcare system’s improvement implementation

Program’s aim. Cardiovascular morbidity and mortality rates in Russia are among the highest in Europe. The aim of this work was to implement a complex healthcare system improvement program in Russia’s Yaroslavl region, dedicated to increasing arterial hypertension treatment efficacy and prevent complications of arterial hypertension. Materials and methods. The program was developed by a group of healthcare professionals of the Department of Healthcare and Pharmacy of Yaroslavl region together with Novartis Pharma Company’s technical advice within the framework of a private-public partnership. The program consisted of several actions aiming to raise the healthcare system’s attention to hypertension. Achievement of target blood pressure (BP) control by every patient seen by physicians of the Yaroslavl region healthcare system became the main goal and leading criteria for assessing hypertension treatment efficacy. Additionally, significant effort was put into patient education on self-control of BP levels and importance of achieving target BP levels in accordance with Russian national clinical guidelines and on adherence to treatment. Within 4 years, program efficacy was evaluated and reinforced by conducting annual cross-sectional questionnaire-based epidemiological studies. Analysis was performed in a representative sample of patients that evaluated BP control level, mean BP levels, systolic BP level distribution by grades, as well as cardiovascular risk factors and concomitant diseases presence and current antihypertensive therapy. In addition, analysis of official statistics on disease incidence and drug sales databases were performed. Results. From 2011 to 2014 BP control level increased significantly: 17% of patients had BP

Изменения в лечении артериальной гипертензии в Ярославской области: результаты, полученные в результате 4 лет реализации комплексной программы по совершенствованию областной системы оказания медицинской помощи

Program’s aim. Cardiovascular morbidity and mortality rates in Russia are among the highest in Europe. The aim of this work was to implement a complex healthcare system improvement program in Russia’s Yaroslavl region, dedicated to increasing arterial hypertension treatment efficacy and prevent complications of arterial hypertension. Materials and methods. The program was developed by a group of healthcare professionals of the Department of Healthcare and Pharmacy of Yaroslavl region together with Novartis Pharma Company’s technical advice within the framework of a private-public partnership. The program consisted of several actions aiming to raise the healthcare system’s attention to hypertension. Achievement of target blood pressure (BP) control by every patient seen by physicians of the Yaroslavl region healthcare system became the main goal and leading criteria for assessing hypertension treatment efficacy. Additionally, significant effort was put into patient education on self-control of BP levels and importance of achieving target BP levels in accordance with Russian national clinical guidelines and on adherence to treatment. Within 4 years, program efficacy was evaluated and reinforced by conducting annual cross-sectional questionnaire-based epidemiological studies. Analysis was performed in a representative sample of patients that evaluated BP control level, mean BP levels, systolic BP level distribution by grades, as well as cardiovascular risk factors and concomitant diseases presence and current antihypertensive therapy. In addition, analysis of official statistics on disease incidence and drug sales databases were performed. Results. From 2011 to 2014 BP control level increased significantly: 17% of patients had BP<140/90 mm Hg in 2011, 23% in 2012, 32% in 2013 and 33% in 2014. In the same time mean BP level reduced from 151/90 to 145/86 mm Hg and share of patients with systolic BP≥180 mm Hg decreased from 10% to 5%. Stroke incidence declined by 20% (from 4,6 to 3,7 per 1000 adult population in 2011 and 2014 respectively) and antihypertensive drug utilization increased by 16% (2014 vs. 2011). Conclusion. A healthcare system improvement program aiming to increase hypertension treatment efficacy resulted in significant improvement in BP control level and substantial decrease in stroke incidence. Continuous improvement is necessary to increase BP control level further resulting in reduction of cardio-vascular mortality and morbidity in the region. Nationwide system for hypertension drug provision could be an instrument of further improvement.

Antihypertensive Efficacy of Fixed Combination Azilsartan Medoxomil / Chlorthalidone in Patients With Uncontrolled Arterial Hypertension

To study effects of a fixed azilsartan medoxomil/chlorthalidone combination (Edarbi Clo) on clinical, ambulatory and central blood pressure (BP) in patients with uncontrolled arterial hypertension (AH)). Patients (n=25) with uncontrolled AH were given fixed azilsartan medoxomil/chlorthalidone combination (40 / 12.5 mg / day) for 4 weeks. After 4 weeks, in patients who did not achieve target BP levels the dose was increased up to 40 / 25 mg / day. Duration of the study was 12 weeks. After 12 weeks of treatment 88 % of patients achieved target clinical BP (.

Effects of Amlodipine/Lisinopril Fixed-Dose Combination on Severity of Left Ventricular Hypertrophy and Parameters of Myocardial Stiffness in Patients With Hypertension

To assess effects of 12 weeks treatment with the amlodipine/lisinopril fixed-dose combination (ALFDC) on the left ventricular (LV) mass index (LVMI), parameters of LV and left atrial stiffness. At phase 1 of the study we examined 44 healthy subjects (21 men, 23 women, mean age 51.5+/-1.0 years) and 60 untreated patients (31 men, 29 women, mean age 53.6+/-0.8 years) with stage II grade 1-2hypertension. Myocardial stiffness parameters, LVMI were calculated using data of transthoracic echocardiography. 2-D speckle tracking echocardiography was used for determination of LV myocardial global longitudinal peak strain (GLPS). All participants underwent ambulatory blood pressure (BP) monitoring, and office BP measurement. At phase 2 a subgroup of 30 untreated patients (16 men, 14 women; mean age 52.7+/-1.11years) received ALFDC in a start dose of 5 mg/10 mg titrated every 14 days to achieve BP<140/90 mm Hg. Therapy in selected doses was continued for 12 weeks thereafter. In hypertensive patients LV GLPS was significantly lower while LA stiffness index higher compared with controls (17.08+/-0.38 vs. 19.91+/-0.41%, p<0.001, and 0.20+/-0.01 vs. 0.16+/-0.01, p<0.01, respectively). There were no significant differences in the LA tissue Doppler derived strain, LV end-systolic elastance, LA expansion index between hypertensive and control groups. After ALFDC therapy BP was significantly (p<0.001) reduced: systolic (S)BP from 154.4+/-2.7 to 130.6+/-1.2, diastolic (D)BP from 96.5+/-1.3 to 83.0+/-0.5 mm Hg. After therapy LV GLPS, LA expansion index, LV diastolic elastance significantly increased (from 17.10+/-0.57 to 18.29+/-0.35%, p<0.01; from 1.47+/-0.08 to 1.68+/-0.08, p<0.001; from 9.25+/-0.99 [10-2] to 10.88+/-1.0 8 [10-2], p<0.05, respectively) while LVMI, LV end-diastolic stiffness, and LA stiffness index significantly (p<0.001) decreased (from 129.4+/-4.5 to 111.8+/-3.3 g/m2, from 0.16+/-0.01 to 0.12+/-0.01 mm Hg/ml, from 0.21+/-0.02 to 0.15+/-0.01, respectively). Change in the LA tissue Doppler derived strain correlated with the change in dynamics of nighttime SBP (r=-0.410, p<0.05). There was direct relationship between change in LV diastolic elastance and nighttime DBP (r=0.424; p<0.05); and an inverse correlation between changes in LV end-diastolic stiffness and dynamics of the daytime SBP and DBP (r=-0.404; p<0.05 and r=-0.364; p<0.05, respectively). Change of LVMI after ALFDC treatment correlated with dynamics of 24-hour, daytime SBP, and daytime pulse pressure (r=0.382, p<0.05, r=0.478, p<0.01, and r=0.364, p<0.05, respectively). In untreated patients with stage II, 1-2 degree hypertension 12-week therapy with ALFDC allowed to achieve target BP levels, reduced severity of LV hypertrophy and improved stiffness parameters of the myocardium.

Resistant hypertension: epidemiology and risk factors

Despite the possibilities of contemporary pharmacotherapy, more than 80% of hypertensive patients do not achieve target blood pressure levels. Besides the obvious reasons – poor adherence of patients to treatment and non-rational therapy, there are other objective risk factors of resistance. Three main modifiable causes of resistant hypertension, that are often underestimated, are considered: obesity, obstructive sleep apnea syndrome and primary hyperaldosteronism. Understanding these mechanisms of resistance and their diagnostic criteria can improve the results of resistant hypertension treatment.

The Role of Central Nervous System Mechanisms in Resistant Hypertension.

Arterial hypertension remains a primary global health problem with significant impact on cardiovascular morbidity and mortality. The low rate of hypertension control and failure to achieve target blood pressure levels particularly among high-risk patients with resistant hypertension has triggered renewed interest in unravelling the underlying mechanisms to implement therapeutic approaches for better patient management. Here, we summarize the crucial role of neurogenic mechanisms in drug-resistant hypertension, with a specific focus on central control of blood pressure, the factors involved in central integration of afferent signalling to increase sympathetic drive in resistant hypertension, and briefly review recently introduced interventional strategies distinctively targeting sympathetic activation.

EFFECT OF «TREAT-TO-TARGET» ANTIRHEUMATIC THERAPY ON DIASTOLIC DYSFUNCTION OF THE LEFT AND RIGHT VENTRICLES IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS DURING 18 MONTHS OF OBSERVATION

Aim. To study the effect of «treat-to-target» antirheumatic therapy on diastolic dysfunction of the left (DDLV) and right (DDLV) ventricles in patients with early rheumatoid arthritis (RA) during 18 months of observation. Material and methods. The study included patients with early RA (n=66; 71% women; age - 56 [46; 61] years) with moderate/high activity (DAS28 5.3 [5.0; 6.2]), seropositive on rheumatoid factor (77%) and/or cyclic citrullinated peptide antibodies (100%), disease modifying anti-rheumatic drugs (DMARD) and glucocorticoids naive. Treatment with methotrexate (MTX) with the escalation of the dose up to 25-30 mg/week subcutaneously was initiated in all the patients. After 3 months in 47 (71%) patients biologics were added to MTX due to its inefficiency. In 18 months remission of RA was achieved in 44% of the patients. 51 (77%) patients had a cardioprotective therapy. The target blood pressure (BP) level was achieved in 38 (58%) patients. Evaluation of traditional cardiovascular risk factors, 24-hour BP monitoring and echocardiography were performed in all patients initially and in 18 months of MTX/MTX + biologics use. Results. After 18 months DDLV incidence decreased by 7% (from 49% to 42%; p>0.05) and DDRV incidence decreased by 5% (from 24% to 17%; p>0.05). A more significant decrease in DDLV incidence [from 23 (62%) to 18 (49%)] and of DDRV incidence (from 12 (32%) to 6 (16%)] (р=0.05), was found in MTX + biologics group than in MTX only group [DDLV incidence remained unchanged - 7 (28%), and DDRV incidence increased from 3(12%) to 4 (16%); p>0.05]. The normalization of left ventricle (LV) diastolic function in early RA patients depended primarily on the efficacy of antihypertensive treatment, and of right ventricle (RV) diastolic function - on the achievement of target BP level and RA remission. Reduced erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) plasma levels were associated with the improved LV diastolic function [E/A LV and ΔESR (r=-0,3; p<0,04), E/A LV and CRP (r=-0,2; p<0.05), A LV and ESR (r=0.3; p<0.01)] and improved RV diastolic function [ΔA RV and ΔCRP (r=0.4; p<0.003), ΔE RV and ΔCRP (r=0.3; p<0.01), E/A RV and DAS28 (r=-0.5; p<0.001), E/A RV and CRP (r=-0,3; p<0.05)] by the 18th month of the study. Conclusion. In early RA patients after 18 months the downward trend of DDLV incidence and a significant reduction of DDRV incidence were found, more expressed in patients treated with MTX + biologics. The achievement of RA remission and target BP level is a prerequisite for the normalization of LV and RV diastolic function and slowing the progression of heart failure.

NEW ASPECTS IN THE TREATMENT OF HYPERTENSION

Hypertension is currently the leading cause of cardiovascular complications (heart attack, stroke) and the resulting deaths of patients. Reduced morbidity and mortality from cardiovascular complications is the main goal of treating patients suffering from high blood pressure (BP). To achieve target BP levels in the arsenal of physicians are five major classes of antihypertensive drugs: angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, β-blockers, diuretics. The choice of antihypertensive drug in concrete clinical situation often complicated and determined by complex factors. Among these presence of risk factors; target organ damage; associated clinical conditions, metabolic syndrome, diabetes, comorbidities; possible individual patient response to antihypertensive drugs of different classes in history; the likelihood of drug interactions; socio-economic factors, including the cost of treatment of hypertension. Promising is the use of angiotensin II receptor blockers ‑ drugs with pleiotropic pharmacological properties that have a multicomponent antihypertensive efficacy, good tolerability, diverse organoprotection that are safe, able to enhance remote prognosis for patients with hypertension. Azilsartan medoxomil is a competitive reversible angiotensin II type 1 receptor antagonist. Azilsartan developing hypotensive effect faster, prolonged and pronounced compared to other sartans (valsartan, candesartan and olmesartan). In addition to antihypertensive action azilsartan medoxomil shows a number of additional pleiotropic effects. These include antithrombotic, antiproliferative and antyfibrotic action. It demonstrates the improvement in glucose tolerance and tissue insulin sensitivity, improves endothelial function, reduces the progression of albuminuria, proteinuria.

Achieving target blood pressure levels in patients with hypertension combined with comorbid type 2 diabetes after a standard multimodelity therapy

More than 80 % of patients with diabetes suffer from arterial hypertension. The combination of these two diseases increase the risk of premature death and disability in patients. The study involved 24 patients with essential hypertension stage II, II and III degree combined with diabetes type II, moderate severity in a state of subcompensation. A combination therapy with ramipril and nebivolol helped to reach the target pressure level after 1 month of treatment, as well as a significant decrease in myocardial stress by 27,28% (p&lt;0,001), which is a sensitive indicator of changes in the heart. The treatment, being a safe option, significantly improved diastolic function of the heart and had a positive effect on lipid and carbohydrate metabolism.

Practical aspects of fixed combinations in the treatment of hypertension

Hypertension is a leading cause of heart attacks and strokes. Reaching target blood pressure (BP) in hypertension is the main condition optimization outlook for cardiovascular morbidity and mortality. To solve this problem in a substantial portion of patients, who are in need of antihypertensive drugs, wherein 70-80% of the target blood pressure can be achieved using a combination therapy. Fixed combinations of antihypertensive drugs increase treatment compliance and provide better organ protection. The new fixed combination of highly selective β-blocker bisoprolol and the calcium antagonist amlodipine can achieve target BP levels in 82,5% of patients with a minimum frequency of side effects.

Anatomical Eligibility of the Renal Vasculature for Catheter-Based Renal Denervation in Hypertensive Patients

This study sought to determine the vascular anatomical eligibility for catheter-based renal artery denervation (RDN) in hypertensive patients. Arterial hypertension is the leading cardiovascular risk factor for stroke and mortality globally. Despite substantial advances in drug-based treatment, many patients do not achieve target blood pressure levels. To improve the number of controlled patients, novel procedure- and device-based strategies have been developed. RDN is among the most promising novel techniques. However, there are few data on the vascular anatomical eligibility. We retrospectively analyzed 941 consecutive hypertensive patients undergoing coronary angiography and selective renal artery angiography between January 1, 2010, and May 31, 2012. Additional renal arteries were divided into 2 groups: hilar (accessory) and polar (aberrant) arteries. Anatomical eligibility for RDN was defined according to the current guidelines: absence of renal artery stenosis, renal artery diameter ≥4 mm, renal artery length ≥20 mm, and only 1 principal renal artery. A total of 934 hypertensive patients were evaluable. The prevalence of renal artery stenosis was 10% (n = 90). Of the remaining 844 patients without renal artery stenosis, 727 (86%) had nonresistant hypertension and 117 (14%) had resistant hypertension; 62 (53%) of the resistant hypertensive and 381 (52%) of the nonresistant hypertensive patients were anatomically eligible for sympathetic RDN. The vascular anatomical eligibility criteria of the current guidelines are a major limiting factor for the utilization of RDN as a therapeutic option. Development of new devices and/or techniques may significantly increase the number of candidates for these promising therapeutic options.

Практические аспекты применения фиксированных комбинаций в лечении артериальной гипертензии

Hypertension is a leading cause of heart attacks and strokes. Reaching target blood pressure (BP) in hypertension is the main condition optimization outlook for cardiovascular morbidity and mortality. To solve this problem in a substantial portion of patients, who are in need of antihypertensive drugs, wherein 70-80% of the target blood pressure can be achieved using a combination therapy. Fixed combinations of antihypertensive drugs increase treatment compliance and provide better organ protection. The new fixed combination of highly selective β-blocker bisoprolol and the calcium antagonist amlodipine can achieve target BP levels in 82,5% of patients with a minimum frequency of side effects.

THE EVALUATION OF ANTIHYPERTENSIVE EFFICACY OF ORALLY-DISPERSING FORM OF PERINDOPRIL IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

Aim. To evaluate the influence of Prestarium A (perindopril as orally dispersing pills, “Les Laboratories Servier”, France) on dynamics of systolic and diastolic arterial pressure and life quality parameters in patients with mild to moderate arterial hypertension. Material and methods. A 12-week prospective observation was performed on 13 women and 9 men in the age of 38 to 60 (mean age 49 y. o.) with mild and moderate arterial hypertension, who received Prestarium A as antihypertensive treatment with the mean daily dose 8,4±2,3 mg. The main endpoints were: 1) changes in mean office blood pressure and of the life quality by EQ-5Q and SF-36 questionnaires at the final visit; 2) intolerability of the drug. Results. In 12 weeks of Prestarium A therapy mean blood pressure significantly decreased from baseline 159,6±12,3 и 101,2±4,3 mmHg to 133,7±7,8 и 83,5±6,2 mmHg (р=0,0009 и р=0,0011, resp., for systolic and diastolic blood pressure; Wilkokson criteria). Target blood pressure (&lt;140 and 90 mmHg) was achieved in 4 weeks in 13 (59%), in 8 weeks in 17 (77%), and in 12 weeks in 20 (86%) patients, and there were no any side effects. Monotherapy by Prestarium A was followed by significant improvement of life quality of the patients according to analogue scale (EQ-5D) from 60,3±6,8 to 75,4±7,3 points (р=0,0041; Wilkockson criteria) and by the scale of physical functioning SF-36 from 48,6±7,6 to 61,6±5,8 points (р=0,0001; Wilkokson criteria). Conclusion. Therapy with Prestarium A in patients with non-complicated mild and moderate arterial hypertension during 12 weeks with average dosage 8,4±2,3 mg made it to achieve target blood pressure levels in 86% patients. Relevant decrease of arterial pressure, achieved by the last visit, was followed by an improvement of lfe quality of the patients, and the therapy itself was perfectly tolerated.

NEW APPROACH TOWARDS THE INTEGRAL ASSESSMENT OF CARDIOVASCULAR STATUS IN PATIENTS WITH ARTERIAL HYPERTENSION

Aim. To assess the potential of the integral assessment of cardiovascular system status in patients with arterial hypertension (AH), based on the evaluation of the parameters of microcirculation (non-invasive digital capillaroscopy) and macrocirculation (pulse wave velocity (PWV) and endothelial function). Material and methods. The study included 188 people aged 40 years and older: 32 patients with systolic blood pressure (BP) levels 120–139 mm Hg (“PreAH” group), 36 patients with Stage 1–2 AH (“AH” group), and 85 AH patients who achieved target BP levels due to antihypertensive therapy (“Treated AH” group). The control group included 35 healthy volunteers, without any signs or symptoms of cardiovascular disease (“Healthy” group). All participants underwent clinical and laboratory examination, including office BP measurement, 24-hour BP monitoring, and echocardiography, the assessment of nailfold microcirculation, pulse wave velocity, endothelial function, as well as the measurement of BP and heart rate. Results. There was an increase in remodelling coefficient (Cv/a) in the groups “PreAH”, “AH”, and “Treated AH”, compared to the “Healthy” group. PWV levels were significantly higher in “PreAH” and “Treated AH” groups than in the “Healthy” group. Based on micro- and macrocirculation parameters assessed, the integral index of cardiovascular status was calculated. The values of this index were significantly higher in the “AH” group. Effective antihypertensive treatment was associated with a reduction in these values. Conclusion. Based on the assessment of a range of micro- and macrocirculation parameters in AH patients, the integral index of cardiovascular status had been developed. This index satisfactorily reflects the dynamics of micro- and macrocirculation in treated AH and, therefore, can be used as an indicator of effective antihypertensive therapy. The complex assessment of macro- and microcirculation provides an opportunity for early AH detection.

CHANGES IN THE PARAMETERS OF 24-HOUR BLOOD PRESSURE MONITORING AND ARTERIAL STIFFNESS IN PATIENTS WITH HYPERTENSION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE TREATED WITH VALSARTAN

Aim. To study changes in the parameters of the 24-hour blood pressure (BP) monitoring and arterial stiffness (AS) in patients with arterial hypertension (HT) and chronic obstructive pulmonary disease (COPD) treated with angiotensin II receptors blocker, valsartan. Material and methods. Men with HT and COPD (n=23), who have been receiving valsartan with starting dose 80 mg/day for 6 months as antihypertensive therapy were included into the study. If target BP was not achieved, correction of the valsartan dose was carried out with the hydrochlorothiazide addition when needed. Clinical examination, 24-hour BP and AS monitoring using BPLab MnSDP-2 monitor ("Petr TELEGIN",Russia), clinical evaluation of COPD were performed. Results. Abnormal circadian BP profile and the elastic properties of arteries were diagnosed in the majority of hypertensive patients with COPD. Valsartan therapy allowed to achieve target BP levels in 100% of patients, normalization of circadian BP profile in 56.5%, improvement in AS parameters: a significant increase in PTT2 (from 89.6±14.3 to 94.4±18.4 ms), reduction of (dP/dt)max (from 566.6±117.9 to 518.8±146.2 mmHg/s), AIx (from -4.0±15.2 to -11.6±20.8 %) as compared to the baseline. Circadian changes in daily parameters of AS in studied patients with the most obvious night-time abnormalities of the elastic properties of arteries were detected. Valsartan intake led to Alx reduction at night-time. Conclusion. Valsartan-based therapy in hypertensive patients with concomitant COPD demonstrated a high antihypertensive efficacy and favorable changes in the elastic properties of the vascular wall that confirm its organoprotective effect.

Rational pharmacotherapy of hypertension. Urapidil potential

Optimizing pharmacotherapy of arterial hypertension (AH) and varied selection of medicines remains an urgent problem for practitioners. However, despite the large variety of effective antihypertensive drugs, the control of blood pressure levels remains inadequate. Most patients require combined therapy with two or more agents to achieve target blood pressure levels, so the choice of second-line therapy is of particular importance. As adjunctive therapy in patients with uncontrolled hypertension a-blockerscan be used, which, in addition to the antihypertensive effect, have a number of other benefits including improved lipid profile and glucose metabolism, as well as reducing the symptoms of benign prostatic hyperplasia. Urapidil provides a-blocking effect and additionally exhibits the central sympatholytic effect which is mediated by stimulation of serotonin 5HT1A-receptor in the central nervous system. The evidence base suggests that the drug has antihypertensive effect in combination with a favorable metabolic profile, and has a good safety profile as well, and has no disadvantages inherent to a-blockers, in particular, the development of reflex tachycardia.

Nifedipine controlled-release 40 mg b.i.d. in Japanese patients with essential hypertension who responded insufficiently to nifedipine controlled-release 40 mg q.d.: a phase III, randomized, double-blind and parallel-group study

This phase III, multicenter, randomized, double-blind, parallel-group study compared the efficacy and safety of nifedipine controlled-release (CR) 40 mg twice daily (b.i.d.) and once daily (q.d.) in 325 Japanese patients with essential hypertension uncontrolled with nifedipine CR 40 mg q.d. (ClinicalTrials.gov record: NCT01287260). The primary endpoint was the change from baseline in trough seated diastolic blood pressure (DBP) after 8 weeks. Nifedipine CR 40 mg b.i.d. showed significantly greater reductions in trough seated DBP (-7.7±0.6 mm Hg vs. -3.6±0.6 mm Hg) and trough seated systolic blood pressure (BP) (-11.1±0.9 mm Hg vs. -3.7±0.9 mm Hg) after 8 weeks of treatment compared with nifedipine CR 40 mg q.d. (both P<0.0001). At week 8, BP target achievement and responder rates were higher with nifedipine CR 40 mg b.i.d. (21.5% and 42.4% vs. 10.3% and 19.5%, respectively). Adverse events considered related to the study drug were reported in 9.0 and 9.7% of patients receiving nifedipine CR 40 mg b.i.d. and q.d., respectively. The frequency of drug-related adverse events commonly reported with nifedipine CR (headache, hot flush, palpitations, peripheral edema, hypotension, dizziness, tachycardia) was low and the results were similar between the treatment groups. In conclusion, a higher dose of nifedipine CR was associated with greater efficacy and a safety profile similar to that of the currently approved dose (40 mg q.d.) in Japanese patients with essential hypertension, and it may offer a valuable treatment choice for patients who do not achieve target BP levels with standard treatment.

COMPARATIVE EFFECTIVENESS OF FIXED-DOSE COMBINATIONS OF LISINOPRIL/AMLODIPINE AND ENALAPRIL/HYDROCHLOROTHIAZIDE

Aim. To compare clinical effectiveness and tolerability of the fixed-dose combinations of lisinopril/amlodipine (Ekvator) and enalapril/hydroch￾lorothiazide (Co-renitec) in high and very-high risk patients with Stage I–II arterial hypertension, whose blood pressure (BP) levels were not normalised during the preceding antihypertensive monotherapy. Material and methods. This blind, randomised (envelope method), parallel study included 27 patients in each group. For 6 months, participants received the first medication (1 tablet a day, in the morning). After the 14-day wash-out phase, they were switched to another medication and received either Ekvator (lisinopril 10 mg plus amlodipine 5 mg) or Co-renitec (enalapril 20 mg plus hydrochlorothiazide 12,5 mg). Results. After 6 months of the treatment, more than 78% of the patients receiving Ekvator achieved target BP levels, in contrast to the participants receiving Co-renitec. Moreover, the treatment with Ekvator was associated with a significant reduction in the myocardial thickness of the posterior left ventricular wall and the carotid-femoral pulse wave velocity, as well as with a significant improvement in lipid metabolism parameters. Conclusion. Ekvator was more effective than Co-renitec in terms of antihypertensive activity, left ventricular hypertrophy reduction, and arterial elasticity improvement, as well as trough/peak ratio improvement.

940 COMBINED EFFECTS OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND CALCIUM CHANNEL BLOCKER IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES-

Objective: We comparatively studied the combined effects of 2 types of calcium channel blocker (CCB) (Azelnidipine tablet: AZL, Nifedipine CR tablet: NCR) in hypertensive patients with diabetes who have failed to achieve target blood pressure levels by usual dose of angiotensin II receptor antagonist (ARB). Methods: AZL 8-16 mg/day or NCR 10-40 mg/day was randomly allocated to 58 hypertensive patients with type 2 diabetes combined with valsartan 80 mg once after breakfast, and the dose was increased until they achieved their target blood pressure <130/80 mmHg (JSH2009). During the study, measurement of blood pressure/heart rate and hematology/urinalysis were performed for 6 months. Results: The doses of CCB were 17.1±9.4 mg/day in the AZL group and 13.2±3.9 mg/day in the NCR group (mean±SD). No significant difference was observed in the patients characteristics between the two groups. Twenty-two patients were with eGFR <60, and 46 patients with normal albuminuria. Although 65% or higher patients achieved target blood pressure level in month 6 in both groups, the blood pressure was significantly lower in the NCR group than the AZL group after month 2, and the rate of target attainment was significantly higher in the NCR group in month 4. The heart rate was decreased significantly in the NCR group. No changes were observed in the blood glucose, HbA1c, and urinary Alb/Cr in both groups, and eGFR was maintained favorably. No significant difference was observed in the changes in blood pressure and renal function in 22 patients with eGFR <60 at the study initiation in both groups. Conclusions: In type 2 diabetes patients with the stage 1-2 nephropathy, both high dose AZL and low dose NCR combined with ARB achieved target blood pressure levels, and could maintain the renal function favorably. It was confirmed that NCR has superior early antihypertensive effect and cost-effectiveness than AZL.