Combination Of Diuretics Research Articles

Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial

ObjectivesThis study compared combination diuretic strategies in acute heart failure (AHF) complicated by diuretic resistance (DR). BackgroundCombination diuretic regimens to overcome loop DR are commonly used but with limited evidence. MethodsThis study was a randomized, double-blinded trial in 60 patients hospitalized with AHF and intravenous (IV) loop DR. Patients were randomized to oral metolazone, IV chlorothiazide, or tolvaptan therapy. All patients received concomitant high-dose IV infusions of furosemide. The primary outcome was 48-h weight loss. ResultsThe cohort exhibited DR prior to enrollment, producing 1,188 ± 476 ml of urine in 12 h during high-dose loop diuretic therapy (IV furosemide: 612 ± 439 mg/day). All 3 interventions significantly improved diuretic efficacy (p < 0.001). Compared to metolazone (4.6 ± 2.7 kg), neither IV chlorothiazide (5.8 ± 2.7 kg; 1.2 kg [95% confidence interval (CI)]: −2.9 to 0.6; p = 0.292) nor tolvaptan (4.1 ± 3.3 kg; 0.5 kg [95% CI: −1.5 to 2.4; p = 0.456) resulted in more weight loss at 48 h. Median (interquartile range [IQR]) cumulative urine output increased significantly and did not differ among those receiving metolazone (7.78 [IQR: 6.59 to 10.10] l) and chlorothiazide (8.77 [IQR: 7.37 to 10.86] l; p = 0.245) or tolvaptan (9.70 [IQR: 6.36 to 13.81] l; p = 0.160). Serum sodium decreased less with tolvaptan than with metolazone (+4 ± 5 vs. −1 ± 3 mEq/l; p = 0.001), but 48-h spot urine sodium was lower with tolvaptan (58 ± 25 mmol/l) than with metolazone (104 ± 16 mmol/l; p = 0.002) and with chlorothiazide (117 ± 14 mmol/l; p < 0.001). ConclusionsIn this moderately sized DR trial, weight loss was excellent with the addition of metolazone, IV chlorothiazide, or tolvaptan to loop diuretics, without a detectable between-group difference. (Comparison of Oral or Intravenous Thiazides vs. tolvaptan in Diuretic Resistant Decompensated Heart Failure [3T]; NCT02606253)

Calcium Channel Blockers Co-prescribed with Loop Diuretics: A Potential Marker of Poor Prescribing?

Prescribing cascades are where a drug adverse reaction is wrongly attributed to the emergence of a new condition, which leads to further drug prescribing. This promotes polypharmacy, adverse drug reactions and therapeutic burden. An example of a prescribing cascade is the co-prescribing of loop diuretics to treat the peripheral oedema caused by calcium channel blocker (CCB) drugs. Although well recognised, this is still a combination of medications taken by millions of people worldwide. CCBs have no prognostic benefit in heart failure and have an absolute risk increase for oedema of around 8-18% (number needed to harm 6-13). In the treatment of hypertension, they also increase the risk of oedema and a new diagnosis of heart failure without having any major advantages over alternative drugs. The best way to manage the oedema caused by CCBs is to switch to an alternative medication. Only where this is not possible or fails to achieve therapeutic goals would the CCB-loop diuretic combination appear to be justified. In many cases, therapeutic practice could be improved by targeting people on CCB-loop diuretic combinations for medication review. This could improve quality of life and reduce polypharmacy, adverse drug reactions, therapeutic burden and financial costs for millions of people worldwide.

Efficacy of chlorthalidone and hydrochlorothiazide in combination with amiloride in multiple doses on blood pressure in patients with primary hypertension: a protocol for a factorial randomized controlled trial

BackgroundThiazide diuretics have demonstrated favorable blood pressure lowering efficacy, but the equivalent doses of their more common agents, chlorthalidone and hydrochlorothiazide, are still unclear. Further, concerns exist regarding adverse metabolic effects, which may be attenuated with the concomitant administration of a potassium-sparing diuretic, such as amiloride. This trial aims to investigate the efficacy of chlorthalidone and hydrochlorothiazide, in combination with amiloride at different doses, for initial management of patients with primary hypertension.Methods/designThis is a factorial (2 × 2) randomized double-blinded clinical trial comparing the association of a thiazide diuretic (chlorthalidone 25 mg/day or hydrochlorothiazide 50 mg/day) with a potassium-sparing diuretic (amiloride 10 mg/day or amiloride 20 mg/day) in patients with primary hypertension. The primary outcome will be the mean change from baseline in 24-h systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring. The secondary outcomes will be the mean change from baseline in daytime and nighttime systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring, mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure, incidence of adverse events, variation of laboratory parameters, and proportion of patients who achieved blood pressure control. The follow-up will last 12 weeks. For a P alpha of 0.05, power of 80%, standard deviation of 9 mmHg, and absolute difference of 6 mmHg on systolic blood pressure on 24-h ambulatory blood pressure monitoring, it will be necessary to study a total of 76 patients. The sample size will be increased by 10% to compensate for losses, resulting in 84 patients being randomized.DiscussionDiuretics are pivotal drugs for the treatment of hypertension. Chlorthalidone and hydrochlorothiazide, in combination with amiloride in multiple doses, will be tested in terms of blood pressure lowering efficacy and safety. Since the intensity of blood pressure reduction is the major determinant of reduction in cardiovascular risk in hypertensive patients, this study will help to determine which combination of diuretics represents the most appropriate treatment for this population.Trial registrationClinicalTrials.gov, NCT03928145. Registered on 25 April 2019. Last update on 29 April 2019.

Analysis of prescription pattern of antihypertensive medication and adherence to Beers criteria in geriatric department of a tertiary care hospital in Mysuru

Background: The objective of the present study was to evaluate the prescription pattern of anti-hypertensive drugs and adherence to Beers’ criteria in geriatric department of JSS Hospital, Mysuru.Methods: An observational, prospective, cross-sectional study was carried out in geriatric department. The basic demographic information and prescriptions of geriatric patients were studied. Descriptive analysis was used to present the results, prescriptions were analysed and checked for adherence to Beers’ criteria.Results: Out of 485 patients, 82.68% received monotherapy, 15.87% received 2-drug combination therapy and 1.4% received 3-drug combination therapy. Among patients receiving monotherapy, angiotensin receptor blockers (49.06%) was the commonest antihypertensive class of drug prescribed. Telmisartan (38.96%) was the commonest drug prescribed. Among 2-drug combination therapy angiotensin converting enzyme inhibitor and Calcium channel blockers were combined commonly. In 3-drug combination therapy angiotensin converting enzyme inhibitor, beta blockers and diuretics were combined commonly. 99.3% of prescriptions were adhered to 2015 American Geriatrics Society Beers criteria.Conclusions: Almost 82% of the patients were treated with monotherapy. The trends in prescribing of anti-hypertensives were in favor of conventional ones such as Angiotensin receptor blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, diuretics, beta blockers and centrally acting alpha agonists. 99.3% of prescriptions were in accordance with the American Geriatrics Society 2015 Updated Beers criteria.

Chronic Effects on Kidney Function by "Triple Whammy" (Combination of Renin and Angiotensin Type Inhibitor, Diuretic Drug and Nonsteroidal Anti-inflammatory Drug)

Recently, there have been reports that the combination of renin angiotensin inhibitors, diuretics, and non-steroidal anti-inflammatory drugs increases the risk of acute kidney injury (AKI). This combination has been dubbed the "Triple Whammy". However, there have been no reports about its chronic effects on the kidney. In this study, we investigated the chronic effects of the "Triple Whammy" on kidney function. There were 203 outpatients who were prescribed this combination in our hospital for 5 years. We excluded patients who could also confirm the combination in the previous year and patients for whom laboratory data were unavailable, thus, leaving a target patient group of 95 patients. The average estimated glomerular filtration rate (eGFR) decreased significantly from 62.6 to 58.9 mL/min/1.73 m2 immediately after administering the combination (p<0.01). Although no patients were diagnosed with AKI within 90 days after being administered the combination, 7.4% of patients exhibited a ≥25% reduction in eGFR compared with that before commencing the combination. Correlation analysis of gender, age, past renal function, and renal function change demonstrated that eGFR before administration of the combination negatively correlated with changes in eGFR (p<0.01). Considering the effects of individual differences, eGFR changes before and after administering the combination were compared using a case-crossover design and eGFR after administering the combination was found to be significantly reduced (p<0.01). Therefore, it appears that the "Triple Whammy" may cause not only AKI but also chronic renal degeneration.

Current perspectives on fixed-dose ACE inhibitordiuretic combination therapy in the management of arterial hypertension

Despite our achievements in modern medicine, arterial hypertension (AH) remains one of the main causes of fatal complications, such as myocardial infarction and acute cerebrovascular accident leading to disability and mortality of patients, including those of working age. The prevalence of hypertension is significantly higher among old and senile age population, however, it has recently tended to increase in young and middle-aged people. Thus, the Russian epidemiological ESSE-RF study, in which representative sample of the Russian population aged 25–64 years were studied, showed that the prevalence of hypertension in individuals of that age group was 44%. It was predicted that the world’s burden of hypertension would increase by 15–20% to approximately 1.5 million people in the year 2015. Due to the high incidence of hypertension and complications associated with hypertension development, further study of pathogenetic mechanisms, development of diagnostic examination methods, prophylactic measures and the search for new treatment options with fixed-dose combination drugs is an important area of modern medicine. This article provides an overview of clinical studies of the components (lisinopril and indapamide) of a rational ACE inhibitor–diuretic combination and a clinical example.

1421Dyskalemias in hypertensive patients treated with combination of antihypertensive drugs: a nested case-control study using Danish national registries

Abstract Aims Little is known about the occurrence of potassium disturbances in relation to combination therapy in hypertension. Using data from Danish electronic registries, we investigated the association between different combinations of antihypertensive therapy and potassium imbalances, in 22,060 individuals, between 1995–2012. Methods Using incidence density matching, two comparison patients without hypokalemia were matched to each corresponding patient with hypokalemia on age, gender, renal function, time from HTN date to date of potassium measurement. The same approach was applied to identify matches for patients with hyperkalemia. The ten most common antihypertensive drug combinations in our population were: (1) Beta-blockers + Angiotensin converting enzyme inhibitors, (2) Angiotensin converting enzyme inhibitors + Thiazides, (3) Angiotensin converting enzyme inhibitors + Thiazides + Potassium supplement, (4) Angiotensin receptor blockers + Other diuretics, (5) Beta-blockers + Angiotensin converting enzyme inhibitors + Potassium supplement (ATC: A12B), (6) Beta-blockers + Calcium channel blockers, (7) Beta-blockers + Thiazides + Potassium supplement, (8) Calcium channel blockers + Angiotensin converting enzyme inhibitors, (9) Calcium channel blockers + Thiazides + Potassium supplement, (10) Other antihypertensive drug combinations. We used conditional logistic regression analysis to examine the risk of developing hypo- and hyperkalemia in relation to different combinations of antihypertensive drugs within one year. The multivariable model was adjusted for serum sodium, malignancy, inflammatory bowel disease, diabetes, alcoholism and beta2-agonists. Results The multivariable analysis showed 10.5 times increased odds for developing hypokalemia if administered Calcium channel blockers + Thiazides + Potassium supplement (95% CI 4.97–22.06) compared to Angiotensin converting enzyme inhibitors + Beta blockers. Other drug combinations significantly associated with increased hypokalemia risk were: Angiotensin converting enzyme inhibitors + Thiazides (OR 5.01, 95% CI 2.32–10.79), Angiotensin converting enzyme inhibitors + Loop + Potassium supplement (A12B) (OR 4.03, 95% CI 1.69–9.62), Angiotensin converting enzyme inhibitors + Thiazides + Potassium supplement (OR 4.16, 95% CI 2.01–8.64) and Calcium channel blockers + Angiotensin converting enzyme inhibitors (OR 4.04, 95% CI 1.72–9.50). None of the ten groups were associated with increased odds for developing hyperkalemia in the multivariable analysis. Cumulative incidence curves for hypokale Conclusion Thiazide diuretics in combination with angiotensin converting enzyme inhibitors or calcium channel blockers were strongly associated with hypokalemia risk within one year from treatment initiation. Acknowledgement/Funding None

Loop diuretic resistance complicating acute heart failure

Acute heart failure hospitalizations complicated by diuretic resistance are associated with worse outcomes. Yet, quantification of the frequency and accompanying risk from loop diuretic resistance is limited by the absence of a comprehensive definition with universal clinical application. Herein, we outline limitations of the current metrics used to identify and define diuretic resistance. We discuss the best available methods to identify and prognosticate outcomes in diuretic resistance. We propose a mechanism-based classification system of diuretic resistance by anatomical location as follows: pre-nephron resistance, pre-loop of Henle resistance, loop of Henle resistance, and post-loop of Henle resistance. Within this paradigm, we compare and contrast historical beliefs of resistance mechanisms with current literature specific to patients with heart failure. We recommend a treatment pathway to restore diuretic efficacy with a literature review of the various combination diuretic strategies and ongoing clinical trials that may impact current best practices.

Modern fixed combinations of antihypertensive drugs in the treatment of arterial hypertension and obesity: can this comorbid pathology be effectively controlled?

Aim. To assess the effect of azilsartan/chlortalidone and irbesartan/hydrochlorothiazide fixed combinations on office, daily peripheral and central blood pressure (BP), daily parameters of aortic stiffness and structural and functional state of the left ventricle in patients with arterial hypertension (AH) and obesity.Material and methods. The study included 46 patients with hypertension and obesity aged 35 to 55 years. In the beginning of the study and after 6 months of treatment with azilsartan/chlortalidone (AZL/C) or irbesartan/hydrochlorothiazide (IRB/H) all patients underwent a comprehensive clinical and instrumental and laboratory examination, including a general examination with anthropometric measurements, office measurement of BP, electrocardiography, echocardiography, 24-hour BP monitoring with analysis of central BP and the main parameters of aortic stiffness, biochemical blood tests.Results. Long-term use of two fixed combinations of sartan and diuretic was accompanied by a significant decrease of office and daily BP. However, in the AZL/С use, this change was more pronounced than in the IRB/H. Also, in the AZL/H group, a significantly larger number of patients reach a normalization of 24-hour BP profile. Both studied drugs significantly reduced central BP, which indicates their positive effect on aortic stiffness. However, a significant change in the daily pulse wave velocity determined by the Vasotens system was not detected. During therapy, in both groups, a decrease in left ventricular myocardial mass indexed by body surface area was revealed. It was more noticeable in the AZL/H group and when height indexed2,7. In both groups, an insignificant decrease in creatinine level and an increase in glomerular filtration rate, more noticeable with the administration of AZL/H, were noted. There were no significant fluctuations in the level of uric acid and patients with AH and obesity.Conclusion. According to studies, AH in obese patients is less well controlled than in patients with normal body weight. AZL/H and IRB/H are effective and safe drugs for the treatment of AH in obese patients. However, long-term treatment of AZL/H allows reaching a more pronounced decrease in peripheral and central BP, improving the structural and functional state of the left ventricular myocardium in comparison with IRB/H.

The relationship between eGFR slope and subsequent risk of vascular outcomes and all-cause mortality in type 2 diabetes: the ADVANCE-ON study

Aims/hypothesisSome studies have reported that annual change in eGFR (eGFR slope) is associated with the future risk of end-stage kidney disease, cardiovascular disease and death in general or chronic kidney disease cohorts. However, the benefits of using eGFR slopes for prediction of major clinical outcomes in diabetes are unclear.MethodsWe used data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial and the ADVANCE Post-Trial Observational Study (ADVANCE-ON). After excluding the first 4 months during which an acute fall in eGFR was induced by the initiation of an ACE inhibitor and diuretic combination agent, eGFR slopes were estimated by linear mixed models, using three measurements of eGFR at 4, 12 and 24 months after randomisation over 20 months, and categorised according to quartiles. Cox regression models were used to evaluate adjusted HRs for the study’s primary outcome, a composite of major renal events, major macrovascular events and all-cause mortality during the subsequent follow-up from 24 months after randomisation.ResultsA total of 8,879 participants (80%) were included in this cohort. The mean age was 65.6 years (SD 6.3), the mean eGFR was 75 ml min−1 (1.73 m)−2 (SD 17) and the median urinary albumin/creatinine ratio was 14 μg/mg (interquartile range 7–38). The mean eGFR slope was −0.63 ml min−1 (1.73 m)−2 year−1 (SD 1.75). Over a median follow-up of 7.6 years following the 20-month eGFR slope ascertainment period, 2,221 participants (25%) met the primary outcome. An annual substantial decrease in eGFR (lowest 25%, <−1.63 ml min−1 [1.73 m]−2 year−1) was significantly associated with the subsequent risk of the primary outcome (HR 1.30 [95% CI 1.17, 1.43]) compared with a stable change in eGFR (middle 50%, −1.63 to 0.33). An annual substantial increase in eGFR (highest 25%, >0.33) had no significant association with the risk of the primary outcome (HR 0.96 [95% CI 0.86, 1.07]).Conclusions/interpretationOur study supports the utility of eGFR slope in type 2 diabetes as a surrogate endpoint for renal outcomes, as well as a prognostic factor for identifying individuals at high risk of cardiovascular disease and all-cause mortality.Trial registry numberClinicalTrials.gov registration no. NCT00145925 and no. NCT00949286

The Obstinate Refractory and Resistance Hypertension

Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) &gt;140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP &gt;140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed.

Interaction of Drugs Used for the Treatment of Cardiovascular Diseases

Combined therapy in cardiology is currently the most recognized method of treatment, especially in patients with hypertension. Approximately in 50 % of patients with hypertension, monotherapy is effective. However to achieve the desired effect in the remaining half of patients, simultaneous administration of two and sometimes three drugs is required. Numerous drugs with a fixed combination of two (and even three) antihypertensive drugs, often used in clinical practice, greatly simplify the dosage regimen of drugs and improve patients’ adherence to treatment. Unfortunately, simultaneous prescription of several drugs increases sharply the probability of inter-drug interaction with the increase in the number of prescribed drugs. The result of drug-drug intereaction may be unpredictable. Therefore, the ability to predict the possible adverse reactions in patients with cardiovascular diseases and to prescribe rationally combined pharmacotherapy is a guarantee of highly efficient and safe treatment.Currently, rational combinations of antihypertensive drugs of different groups make hypertension therapy more comfortable and increases patients’ adherence to treatment. The authors present topical combinations of antihypertensive drugs in one drug: angiotensin converting enzyme inhibitor + diuretic, β-adrenoblocker + diuretic; diuretic + angiotensin receptor antagonist; calcium antagonist + angiotensin receptor antagonist; calcium antagonist + β-adrenoblocker, and others.The article presents an overview of both rational (calcium antagonist + diuretic, β-adrenoblocker + diuretic,) and irrational (angiotensin converting enzyme Inhibitor + potassium-sparing diuretic, angiotensin receptor blocker + potassium-sparing diuretic) combinations of antihypertensive drugs. Combinations of some hypotensive and antianginal drugs with drugs of other groups with a high risk of adverse reactions are presented.

Efficacy of triple diuretic treatment in continuous ambulatory peritoneal dialysis patients: A randomized controlled trial

BackgroundThe efficacy of combined diuretic treatment in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known.MethodsIn a single-center, double-blinded, randomized controlled trial, we randomly assigned 51 adult CAPD patients to receive furosemide 1,000 mg/day, hydrochlorothiazide 100 mg/day, and spironolactone 50 mg/day (triple diuretics [TD] group) or furosemide 1,000 mg/day plus placebo (single diuretic [SD] group) for 6 months. The primary outcome was the difference in daily urine output at the 3rd and 6th month of the study compared to baseline (ΔUO) between the SD and TD group. Secondary outcomes were urinary sodium (UNa) and potassium (UK) excretion and overhydration (OH) measured by bioimpedance at 3 and 6 months compared to baseline (ΔUNa, ΔUK, and ΔOH, respectively) and daily glucose exposure (g/day).ResultsForty-three of 51 patients completed the 6-month trial. The ΔUO at 3 and 6 months was significantly higher in the TD group compared to the SD group (386.32 ± 733.92 mL/day vs. −136.25 ± 629.08 mL/day, P < 0.001, at 3 months; 311.58 ± 640.31 mL/day vs. 120.00 ± 624.07 mL/day, P < 0.001, at 6 months) but there was no significant difference in ΔUNa and ΔUK excretion. Hydration status was significantly better in the TD group (ΔOH 1.84 ± 2.27 L vs. 0.44 ± 1.62 L, P = 0.03, at 3 months; 1.49 ± 2.82 L vs. −0.48 ± 2.61 L, P = 0.02, at 6 months). There was no serious adverse event in this study.ConclusionFor end-stage renal disease patients on CAPD, the combination of furosemide, hydrochlorothiazide, and spironolactone results in higher urine output and better volume control compared to furosemide alone.

Influence of correction of secondary hyperparathyroidism on the pulse wave indicators and mineral density of bone tissue in middle‑aged women with uncomplicated arterial hypertension

The aim — to assess the effect of correction of secondary hyperparathyroidism on the background of deficiency and insufficiency of 25 (OH) vitamin D on the parameters of central blood pressure (BP) and pulse wave, bone mineral density (BMD) in elderly patients with controlled uncomplicated arterial hypertension (AH).Materials and methods. The study included 44 women of middle age (69.04 ± 0.72 years) with AH of stage II, 2nd degree (main group) and 30 practically healthy patients (control group) of middle age (69.0 ± 1.21 years). The duration of the postmenopausal period in the main group averaged 18.40 ± 0.85 years, in the control group — 19.40 ± 1.18 years (p > 0.05). At the time of randomization AH was controlled, patients received antihypertensive therapy (AHT) based on a fixed combination of dihydropyridine calcium channel blocker (CCB) and thiazide diuretic (Aryfam, Servier, France) at the dose of 5 mg/1.5 mg or 10 mg/1.5 mg (BP levels < 140/90 mm Hg). To correct the deficiency/insufficiency of 25 (OH) vitamin D3 all patients of the main group were additionally prescribed vitamin D (in a daily dose of 3000 — 4000 IU per day) and the ossein hydroxyapatite compound in a dose 830 mg (291 mg of ossein which consists of non‑collagen peptides and proteins (75 mg) and collagen (216 mg), hydroxyapatite (444 mg) including calcium (178 mg) and phosphorus (82 mg) (Osteogenone, Pierre Fabre Medicare Productions, France) for 2 tablets 2 times a day for 6 months. After 6 months, the patients of the main group were divided into two subgroups. In I subgroup 18 women continuously received the therapy, in II subgroup (n = 21) the patients did not follow the recommendations for the correction of vitamin D metabolism. All patients had a general clinical and laboratory examination, arterial pressure monitoring and echocardiography. Parameters of central hemodynamics and arterial stiffness were measured using SphygmoCor (AtCor Medical, Australia) with the definition of central blood pressure (cBP), augmentation pressure (AP), augmentation index (AIx), including normalized one for a pulse rate of 75 beats/min (AIx75), amplification pressure (PPampl), carotid radial (PWVrad) and carotid‑femoral pulse wave velocity (PWVfem). Mineral density of bone tissue was investigated using Hologic Discovery apparatus. To evaluate the Trabecular Bone Score (TBS), the TBS iNsight method developed by Med‑Imaps (France) was used.Results and discussion. The patients of the main group had statistically significant increase in AP, AIx, AIx75 — by 37.7 %, 57.5 % and 58.2 %, respectively (p < 0.001), PWVrad — by 31 %, PWVfem — by 32 % (all p < 0.001) and decrease in PPampl — by 20.8 % (p < 0.001) in comparison with the control group at the time of inclusion in the study. When comparing indicators of applanation tonometry in patients of I subgroup, in the absence of significant changes in brachial and central blood pressure, AR, AIx75 and PPampl significantly decreased — by 18.0 %, 11.5 % and 5.0 %, respectively, (all p < 0.05) compared with the indicators of II subgroup. The marker for bone remodeling — propeptide prokologen type I was unchanged in both subgroups; the level of 25 (OH) of vitamin D was normalized in I subgroup, which was also accompanied by the normalization of parathyroid hormone levels and b‑CTx resorption marker. Bone mineral density increased at the level of the femoral neck in patients of I subgroup (p < 0.05).Conclusions. 6 months comprehensive hypotensive, hypolipidemic therapy and correction of secondary hyperparathyroidism, 25 (OH) vitamin D deficiency/insufficiency showed greater effectiveness in improving of the index of arterial stiffness and structural and functional state of bone tissue compared to therapy without vitamin D and ossein‑hydroxyapatite compounds in patients with uncomplicated hypertension.

Arterial Hypertension in Patients Aged 15 Years and Over in the Cardiology Department of Sikasso Hospital in Mali: About 250 Cases

Introduction: High blood pressure is a global public health problem due to its high prevalence and multiple complications that often lead to major disability. It is a major cardiovascular risk factor for often late diagnosis. It is emerging in Africa, particularly in Mali. Objective: To determine the epidemiological, diagnostic and progressive aspects of high blood pressure in patients 15 years of age or older. Patients and methods: This is a descriptive cross-sectional study over a two-year period (June 1, 2008 to May 31, 2010) in the Cardiology Department of Sikasso Hospital in any patient aged 15 years and over admitted for high blood pressure. Results: Two hundred and fifty patients were selected, representing a hospital prevalence of 18.2%. High blood pressure was most common in patients 50 years of age and older (65.6%), followed by those 19 to 49 years of age (30%) and those 15 to 18 years of age. The average age of the population was 50 years (15-92 years) with a male predominance of 61.6% and a sex ratio of 1.6. The predominance of traditional housewives and farmers was 30% and 26.4%. The notion of a family history of high blood pressure was found in 56.4% of cases. High blood pressure grade 3 according to the classification of the World Health Organization was mostly found in our patients (64%). Biological abnormalities were dominated by hyperglycemia (14%), hypercreatininemia (8%). The main clinical manifestations were headache (40%), dyspnea (20%) and vertigo (16%). On physical examination, there were mainly signs of heart failure (50%), arrhythmia (12%), heart murmur (28%), hemiplegia (10%). The electrocardiogram showed left ventricular hypertrophy in 79.2% of cases, left atrial hypertrophy (16.4%), repolarization disorder (3.2%), atrial fibrillation (1.2%). Chest x-rays showed cardiomegaly in 67.2%. Echocardiographic abnormalities were left ventricular hypertrophy (64.8%), left atrial dilation (16.4%), left ventricular systolic dysfunction (14.4%). Therapeutically, diuretic combination with conversion enzyme inhibitors was the most prescribed treatment (58%), followed by combination of calcium channel blockers and conversion enzyme inhibitors (15.6%), calcium channel blockers (18%), conversion enzyme inhibitors (4.4%), beta-blockers (4%). The low-salt diet and physical activity were constantly recommended. Complications were hypertensive retinopathy (33.2%), heart failure (25.2%), stroke (24.8%), renal failure 4.8%. Conclusion: High blood pressure is a major public health problem. This work identified a high hospital prevalence of high blood pressure in patients aged 15 years and older with a clear male predominance. Late diagnosis is responsible for serious complications that often lead to major disabilities.

Sequential versus Combination Treatment Using Steroids and Diuretics for Acute Low-Frequency Sensorineural Hearing Loss: A Noninferiority Trial.

Acute low-frequency hearing loss (ALHL) is typically treated with combination therapy, including steroids and diuretics. To avoid unnecessary use of steroids we proposed a method of sequential administration using these two drugs, and compared the efficacy of our protocol with that of existing combination treatments. A prospective, randomized, open-label, single-blind, noninferiority clinical trial was conducted to investigate whether the effectiveness of sequential treatment is noninferior to that of combination treatment for ALHL. Ninety-two patients with ALHL received either steroids and diuretics simultaneously for 2 weeks (combination group), or diuretics for 2 weeks followed by steroids for another 2 weeks if they did not respond to diuretic treatment (sequential group). The primary outcome measure was a change in mean hearing threshold at three frequencies (125, 250, and 500 Hz) at 4 weeks after treatment. The mean hearing threshold of the low frequencies improved 20.0 and 17.2 dB in the combination and the sequential group, respectively. The 95% lower confidence interval was -8.0 dB and noninferiority was established at p < 0.05. At 4 weeks after treatment, the complete recovery rate was 80.5 and 82.9% in the combination and sequential groups, respectively. This is the first study on ALHL treatment following the establishment of Consolidated Standards of Reporting Trials (CONSORT). The sequential treatment is not inferior to combination treatment for ALHL, and therefore may be a better treatment guideline for ALHL considering that patients receive less steroid exposure and smaller restrictions in diuretic use compared with steroids.

The combination of angiotensin converting enzyme inhibitors, diuretics and non-steroidal anti-inflammatory drugs in the routine community pharmacy settings in Poland: The unrecognized problem of ‘Triple Whammy’. A pilot analysis.

Background- The aim is to analyze how the legal system in the European Union that deals with the public health emergencies in terms of organization and readiness to respond to public health emergencies. Methods - The method used is desk research, based on the current secondary scientific literature, both from the online resources and from the variant publications. Results - The primary responsibility for responding to public health emergencies falls within the domain of the EU Member States, while the EU action is intended to complement the national policies of the EU Member States and to coordinate and support their actions. The Commission plays a vital role, both in coordinating and in exchanging the information among the EU Member States. Based on the experience with the public health emergencies the Commission initiated new legislation in 2011 which resulted in a new Decision No. 1082/2013 on Serious Cross-Border Threats to Health. The national authorities are required to send to all authorities connected through the network data related to serious threats to public health. Conclusion - There is still a room for collaboration improvement. Further actions should be undertaken to bring the coordination and network for the public health emergencies surveillance, preparedness and response planning to a higher level.

Effectiveness of Chrono-Pharmacotherapy Depending on the Salt Sensitivity of Patients with Arterial Hypertension and Diabetes Mellitus Type 2

Aim. To study the effect of two regimens of combined antihypertensive therapy during the day on daily monitoring of arterial pressure, central aortic pressure, and arterial stiffness, depending on the salt sensitivity of hypertensive patients with diabetes mellitus type 2. Material and methods. 130 hypertensive patients with type 2 diabetes mellitus were included into the study. They were divided into 2 subgroups: salt-sensitive (group 1) and salt-resistant (group 2), and then randomized to subgroups A and B of ongoing therapy: in the morning ramipril and indapamide retard, bedtime – amlodipine (subgroup 1A and 2A); or in the morning amlodipine and indapamide retard, bedtime – ramipril (subgroup 1B and 2B). Initially and after 24 weeks of antihypertensive therapy, 24-hour blood pressure monitoring was performed, the indices of central aortic pressure and arterial stiffness were determined. Results. After 24 weeks, in all subgroups, there was a significant positive dynamics of the parameters of 24-hour blood pressure monitoring, central aortic pressure and arterial stiffness indices. In the subgroup 1В, it was registered a significant improvement in the majority of parameters of 24-hour blood pressure monitoring (decrease in 24-hours systolic BP by 24.4%, 24-hours diastolic BP by 22.1%; p&lt;0.05), central aortic pressure (decrease in aortal systolic BP by 15.9%, aortal diastolic BP by 20.8%; p&lt;0.05) and vascular wall stiffness parameters (decrease in pulse wave velocity by 13.8%; p&lt;0.05) in comparison with group 1A (decrease in 24-hours systolic BP by 17.5%, 24-hours diastolic BP by 14.6%, aortal systolic BP by 12.7%, aortal diastolic BP by 9.7%, pulse wave velocity by 9.2%; p&lt;0.05 in comparison with the group 1B). In the case of salt-resistant patients, there were comparable positive changes in the parameters of 24-hour blood pressure monitoring, central aortic pressure and arterial stiffness indices against the background of both dosing regimens during the day. Conclusion. In the study, it was demonstrated the more pronounced antihypertensive and vasoprotective efficacy of the combination of thiazide-like diuretic with calcium channel blocker in the morning and ACE inhibitor in bedtime compared to the alternative regimen of prescribed pharmacotherapy in salt-sensitive patients, and comparable efficacy of both regimens in salt-resistant hypertensive patients with diabetes mellitus type 2.

LEVOSIMENDAN – A VALUABLE PLAYER IN THE TREATMENT OF A RIGHT-SIDED HEART FAILURE

A 66 year-old obese man, suffering from type 2 diabetes, high blood pressure, chronic nephropathy in stage 4, permanent atrial fibrillation accompanied by bradycardia was admitted to a cardiology ward with the signs and symptoms of acute right-sided heart failure. A standard therapy was used including combined diuretics therapy. In spite of the applied methods and pharmaceuticals, no significant reduction of the body weight neither improvement in cardiovascular capacity or renal parameters were observed. Due to the ineffectiveness of the standard combined pharmacotherapy applied in the case of the acute circulatory failure, the resistance to diuretics was recognized and as a result of the above, infusion of levosimendan was decided to be applied. This therapy resulted in rich diuresis, significant loss in body weight and considerable improvement in cardiovascular capacity which allowed to continue further diagnostics and appropriate invasive treatment. The article describes current knowledge on the place of levosimendan and its application in the treatment of an right-sided heart failure.

Differences in the effects of various classes of antihypertensive drugs in combination therapy on indicators of arterial hemodynamics, vascular wall stiffness and structural-functional state of heart in patients with arterial hypertension of 1 — 2 degrees

The aim — to compare the effect of 6‑month treatment of patients with arterial hypertension (AH) of 1 — 2 degrees with angiotensin converting enzyme (ACE) or angiotensin II receptor blockers (ARB) in combination with a thiazide diuretic (indapamide) and dihydropyridine calcium channel blockers (CCB) in combination with a diuretic on indicators of brachial and central arterial pressure (AP), elastic properties of the arteries and the structural and functional state of the heart, depending on age.Materials and methods. The study included 320 patients (156 men and 164 women) aged from 35 to 80 years (mean age 62.8 ± 0.61 years) with uncomplicated AH of stage I — II, degree 1 — 2 (62.0 % and 38, 1 %, correspondingly). Depending on age, the patients were divided into two groups: 0.05). In both subgroups of patients aged 0.05). In the group treated with Arifam, the baseline HR values correlated with AP (r = –0.357, p 0.05). In patients aged ≥ 65 years, the antihypertensive effect of therapy with the combination of ACE inhibitor/ARB and indapamide was not accompanied by changes in MMI LV and indicators of LV systolic and diastolic function (all p > 0.05). In the group treated with Arifam there was a decrease in end‑diastolic and end‑systolic volumes (by 9.7 % (p 0.05).Conclusions. In spite of the same positive effect of 6‑month therapy with combinations of ACE inhibitors/ARB with indapamide and BPC with indapamide on brachial and central AP in older patients with hypertension of 1 — 2 degrees, the fixed combination of BPC amlodipine with indapamide (Arifam) had an advantage over the combination based on an ACE inhibitor (ARB) regarding the reduction of brachial, central, mean brachial and mean central AP, augmentation, pulse wave velocity, MMI of LV, left atrium volume index, E/e’ of LV, which was associated with an increase in heart rate (an average of 4.6 per 1 min).