Diuretic Group Research Articles

#4949 COMBINED ORAL DIURETICS: A BETTER ALTERNATIVE FOR NEPHROTIC EDEMA THAN INTRAVENOUS FUROSEMIDE?

Abstract Background and Aims Edema is a serious complication of nephrotic syndrome and is the main reason why patients usually address to a doctor. There is no guideline on managing nephrotic edema. Besides non pharmacological interventions such as sodium and water restrictions, most doctors would choose high doses of intravenous furosemide as the first option, but still many patients fail to properly decrease their volume overload, as they become diuretic resistant. Amiloride, an ENaC mediated diuretic, is an optimistic management option, especially when used with other diuretics. The aim of the present study was to assess the non inferiority of the combined oral diuretics furosemide and the fixed combination of hydrochlorothiazide/amiloride diuretics with intravenous furosemide in diuretic resistant nephrotic edema. Method We conducted a prospective randomized trial in 22 patients with diuretic resistant nephrotic edema. Based on a computer-generated randomization we assigned patients to receive either intravenous furosemide (40 mg bolus and then continuous administration of 5 mg/h) or oral furosemide (40 mg/day) and hydrochlorothiazide/amiloride (50/5 mg/day). Clinical and laboratory measurements were performed daily, for five days (body weight, urinary output, blood pressure and hydration status by bioimpedance twice, creatinine, urea, albumin, hematocrit, Na, K, Ca, Mg, bicarbonate, pH). The primary outcome was weight and hydration status change from baseline to day 5. Secondary outcomes were safety outcomes (low blood pressure, severe dyselectrolytemia, acute kidney injury or aggravated hypervolemia). Results The patients were equally distributed between the two groups. Mean age was 47,77±15,97 (54,5% females and 45,5% males). Half of the patients had membranous nephropathy (45,5%), followed by minimal change disease (22,7%) and lupus nephritis (9,1%). 86,4% of patients had their first episode of nephrotic edema. The mean weight decrease was of significantly larger magnitude in the combined oral diuretics group compared with the intravenous furosemide group (-7,97±2,83 [SD] vs -4,5±2,6 [SD] kg; p = 0,018). Although the increase in 24-hour urine sodium excretion was higher in combined oral diuretics as compared to intravenous furosemide group, this increment was not statistically significant different (26,79±33,48 [SD] vs 16,04±42,81 mmol/24 h [SD]; p = 0,5). Mean values for changes in systolic and diastolic BP, 24-hour urine volume, hydration status measured by bioimpedance were not significantly different between the two groups. A total of 5 patients could not be followed through, 4 in the intravenous furosemide (two patients experienced low blood, one patient had no response to iv furosemide and one patient suffered from insomnia due to iv pump) and one patient in the oral combination of diuretics group had severe hyperkalemia (>6,5 mmol/l). Conclusion Combined oral diuretics with furosemide, amiloride and hydrochlorothiazide is more effective and safer than intravenous furosemide for the treatment of refractory nephrotic edema. These results make amiloride a promising diuretic and further trials with larger sample sizes and longer follow-up are needed in this regard.

Safety and Efficacy of Empagliflozin and Diuretic Use in Patients with Heart Failure and Preserved Ejection Fraction

The diuretic effect of sodium-glucose cotransporter 2 inhibitors may result in interaction with background diuretic therapy in patients with heart failure and preserved ejection fraction (HFpEF). To assess the safety and efficacy of empagliflozin in combination with background diuretic therapy and the association of empagliflozin with the need for conventional diuretics. This was a post hoc analysis of the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved). EMPEROR-Preserved was a phase 3, randomized, placebo-controlled, double-blind clinical trial conducted from March 2017 to April 2021. Patients with class II to IV heart failure and left ventricular ejection fraction greater than 40% were included. Of 5988 patients enrolled, 5815 (97.1%) had baseline data on diuretic use and were included in this analysis, which was conducted from November 2021 to August 2022. Participants in EMPEROR-Preserved were randomized to empagliflozin or placebo. In this analysis, participants were divided into 4 subgroups: no diuretics and furosemide-equivalent diuretic dose of less than 40 mg, 40 mg, and greater than 40 mg at baseline. The main outcomes of interest were first hospitalization for heart failure (HHF) or cardiovascular death (CV death) and its components. Association of empagliflozin vs placebo with outcomes by baseline diuretic status (no diuretic vs any dose) and dose (no diuretic, <40 mg, 40 mg, and > 40mg) was assessed. Association of empagliflozin use with changes in diuretic therapy was also studied. Among 5815 patients (mean [SD] age, 71.9 [9.4] years; 2594 [44.6%] female) with known baseline diuretic use, 1179 (20.3%) were not taking diuretics, 1725 (29.7%) were taking less than 40 mg, 1772 (30.5%) were taking 40 mg, and 1139 (19.6%) were taking greater than 40 mg. In the placebo arm, patients with higher diuretic doses had worse outcomes. Empagliflozin decreased the risk of HHF or CV death, regardless of background diuretic status (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93] for the diuretic group vs HR, 0.72; 95% CI, 0.48-1.06 for the nondiuretic group; P for interaction = .58). Similarly, diuretic status was not associated with changes in improvements in first HHF, total HHF, rate of decline in estimated glomerular filtration rate, and Kansas City Cardiomyopathy Questionnaire 23 clinical summary score with empagliflozin. Findings were consistent when patients were categorized by diuretic dose. Empagliflozin was associated with a decreased likelihood of diuretic dose escalation (HR, 0.74; 95% CI, 0.65-0.84) and an increased likelihood of de-escalation (HR, 1.15; 95% CI, 1.02-1.30). Empagliflozin was associated with an increased risk of volume depletion in patients taking diuretics (HR, 1.34; 95% CI, 1.13-1.59). In this study, treatment with empagliflozin was similar regardless of diuretic use or dose. Empagliflozin use was associated with decreased conventional diuretic dosing. ClinicalTrials.gov Identifier: NCT03057951.

Clinical phenotypes according to diuretic combination in acute heart failure

BackgroundThe treatment of congestion in heart failure (HF) is a challenge despite the therapeutic arsenal available. The aim of this study was to analyze different combinations of diuretics used to resolve congestion in patients admitted for decompensated HF and to define clinical profiles according to these treatments. MethodsSingle-center study of 1,559 patients admitted for decompensated HF was done between 2016 and 2020. Patients were grouped according to the diuretic combination that led to clinical stabilization and discharge from the hospital: (1) Loop diuretic. (2) Loop diuretic + distal tubule (antialdosterone ± thiazides). (3) Loop diuretic + distal + proximal tubule (acetazolamide ± SGLT2 inhibitor). (4) Loop diuretic + distal tubule + collecting duct (tolvaptan). (5) Loop diuretic + distal + proximal + collecting duct. Based on these diuretic combinations, profiles with clinical, analytical, and echocardiographic differences were established. ResultsThere were more previous hospitalizations in groups 4 and 5 (p = 0.001) with a predominance of pulmonary congestion in profiles 1 and 2 and systemic congestion in 3, 4, and 5. Creatinine and CA125 were higher in profiles 4 and 5 (p = 0.01 and p = 0.0001), with no differences in NT-proBNP. Profiles 4 and 5 had a higher proportion of dilatation and depression of right ventricular (p = 0.0001) and left ventricular (p = 0.003) function. Diuretic therapy-defined groups showed difference in clinical characteristics. ConclusionsThe diuretic treatment used identifies five clinical profiles according to the degree of congestion, renal function, CA125, and right ventricular functionality. These profiles would guide the best diuretic treatment on admission.

Efficacy of tolvaptan in postoperative volume therapy for acute Stanford type A aortic dissection

BackgroundDespite the increasing application of tolvaptan in cardiac surgery, there is no information on the use of tolvaptan in Stanford patients with type A aortic dissection. This study aimed to evaluate the postoperative clinical effects of tolvaptan in patients with type A aortic dissection after tafter surgery.MethodsA retrospective analysis was performed on 45 patients treated for type A aortic dissection in our hospital from 2018 to 2020. These included 21 patients who were treated with tolvaptan (Group T) and 24 patients who received traditional diuretics (Group L). The hospital's electronic health records were used to obtain perioperative data.ResultsGroup T did not differ significantly from Group L in terms of the duration of mechanical ventilation, postoperative blood required, length of catecholamine use, or the amount of intravenous diuretic drugs administered (all P > 0.05). The development of postoperative atrial fibrillation was significantly less in the tolvaptan group (P = 0.023). The urine volumes and change in body weight loss were slightly higher in group T than in group L but the differences were non-significant (P > 0.05). Serum potassium, creatinine, and urea nitrogen levels did not differ between the groups in the week after surgery, At the same time, sodium was significantly higher in the Group T group on day 7 after transfer from the ICU (P = 0.001). In Group L, sodium levels were also elevated by day 7 (P = 0.001). On days 3 and 7, serum creatinine and urea nitrogen levels increased in both groups (both P < 0.05).ConclusionsBoth tolvaptan and traditional diuretics were found to be effective and safe for patients with acute Stanford type A aortic dissection. Moreover, tolvaptan may be associated with reducing the incidence of postoperative atrial fibrillation.

Predictors of Poor Very Early Diuretic Response and Effectiveness of Early Tolvaptan in Symptomatic Acute Heart Failure.

Diuretic response (DR) in patients with symptomatic acute decompensated heart failure (ADHF) has an impact on prognosis. This study aimed to identify predictive factors influencing acute 6h poor DR and to assess DR after early administration of tolvaptan (TLV). This multicenter retrospective study included 1670 patients who were admitted for ADHF and received intravenous furosemide within 1h of presentation in clinical scenario 1 or 2 defined based on initial systolic blood pressure ≥100mmHg with severe symptoms (New York Heart Association class III or IV (n=830). The score for the poor DR factors in the very acute phase was calculated in patients treated with furosemide-only diuretics (n=439). The DR to TLV administration was also assessed in patients who received an additional dose of TLV within 6h (n=391). The time since discharge from the hospital for a previous heart failure <3 months (odds ratio [OR] 2.78, 95% confidence interval [CI] 1.34-5.83; p=0.006), loop diuretics at admission (OR 3.05, 95% CI 1.74-5.36; p<0.0001), and estimated glomerular filtration rate (eGFR) <45mL/min/1.73m2 (OR 2.99, 95% CI 1.58-5.74; p=0.0007) were independent determinants of poor DR. The frequency of poor DR according to the risk stratification group was low risk (no risk factor), 18.9%; middle risk (one risk factor), 33.1%; and high risk (two to three risk factors), 58.0% (p<0.0001). All risk groups demonstrated a significantly lower incidence of poor DR with early TLV administration: 10.7% in the early TLV group versus 18.9% in the loop diuretics group (p=0.09) of the low-risk group; 18.4% versus 33.1% (p=0.01) in the middle-risk group, and 20.2% versus 58.0% (p<0.0001) in the high-risk group. Early administration of TLV in patients with predicted poor DR contributed to a significant diuretic effect and suppression of worsening renal function.

Women on diuretics have a higher risk of hospital admission because of hyponatremia than men.

Recent studies suggest that women are more susceptible to diuretic-induced hyponatremia resulting in hospital admission than men. The aim of this study was to confirm whether these sex differences in hyponatremia-related hospital admissions in diuretic users remain after adjusting for several confounding variables such as age, dose, and concurrent medication. In a case-control design nested in diuretic users, cases of hyponatremia associated hospital admissions between 2005 and 2017 were identified from the PHARMO Data Network. Cases were 1:10 matched to diuretic users as controls. Odds ratios (OR) with 95%CIs were calculated for women versus men and adjusted for potential confounders (age, number of diuretics, other hyponatremia-inducing drugs, chronic disease score) using unconditional logistic regression analysis. A subgroup analysis was performed for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists). Women had a statistically significantly higher risk of a hospital admission associated with hyponatremia than men while using diuretics (OR 1.86, 95%CI 1.64-2.11). Adjusting for the potential confounders resulted in an increased risk for women compared to men (ORadj 2.65, 95% CI 2.31-3.04). This higher risk in women was also seen in the three subgroup analyses after adjustment. Our findings show a higher risk of hyponatremia-related hospital admission in women than men while using diuretics. Further research is needed to understand the underlying mechanism of this sex difference to be able to provide sex-specific recommendations.

Canagliflozin independently reduced plasma volume from conventional diuretics in patients with type 2 diabetes and chronic heart failure: a subanalysis of the CANDLE trial.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce the risk of heart failure progression and mortality rates. Moreover, osmotic diuresis induced by SGLT2 inhibition may result in an improved heart failure prognosis. Independent of conventional diuretics in patients with type 2 diabetes (T2D) and chronic heart failure, especially in patients with heart failure with preserved ejection fraction (HFpEF), it is unclear whether SGLT2i chronically reduces estimated plasma volume (ePV). As a subanalysis of the CANDLE trial, which assessed the effect of canagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP), we examined the change (%) in ePV over 24 weeks of treatment based on the baseline level associated with diuretic usage. In the CANDLE trial, nearly all patients were clinically stable (NYHA class I-II), with approximately 70% of participants presenting a baseline phenotype of HFpEF. A total of 99 (42.5%) patients were taking diuretics (mostly furosemide) at baseline, while 134 (57.5%) were not. Relative to glimepiride, canagliflozin significantly reduced ePV without worsening renal function in patients in both groups: -4.00% vs. 1.46% (p = 0.020) for the diuretic group and -6.14% vs. 1.28% (p < 0.001) for the nondiuretic group. Furthermore, canagliflozin significantly reduced serum uric acid without causing major electrolyte abnormalities in patients in both subgroups. The long-term beneficial effect of SGLT2i on intravascular congestion could be independent of conventional diuretic therapy without worsening renal function in patients with T2D and HF (HFpEF predominantly). In addition, the beneficial effects of canagliflozin are accompanied by improved hyperuricemia without causing major electrolyte abnormalities.

Comparative Pharmacoepidemiological Assessment of Antihypertensive Drugs Administration Structure in Pregnant Women in Routine Medical Practice in Kursk and Chisinau

Aim. To study the structure of antihypertensive drugs prescription in pregnant women in routine practice in Kursk and Chisinau.Material and methods. The study design was observational descriptive cross-sectional. Authors conducted a survey of doctors in medical organizations in Kursk and Chisinau in 2017-2018.Results. Respondents from Kursk and Chisinau preferred methyldopa in prescriptions of central alpha-adrenergic receptor agonists. Doctors from Chisinau used clonidine in 14.3% of cases. The leading place in the group of calcium channel blockers belonged to short-acting nifedipine. Among beta-blockers in Kursk, doctors most often prescribed bisoprolol (43.3%), metoprolol (21.7%) and nebivolol (13.3%), while in Chisinau the preference was given to metoprolol (32.1%), atenolol (19.6%) and bisoprolol (16.1%). From the group of diuretics, Kursk doctors mainly prescribed hydrochlorothiazide (10%), indapamide (6.7%); in Chisinau, indapamide was the leader (19.6%), hydrochlorothiazide was used less frequently (7,1%). From the class of alpha-blockers, prazosin occupied the leading position among respondents in Kursk, and terazosin in Chisinau.Conclusion. The priority drug classes in both regions were calcium channel blockers, central alpha-adrenergic receptor agonists and beta-blockers. A small number of not recommended drugs prescriptions have been registered. In general, the prescribed treatment corresponded to the current guidelines and protocols for the management of patients with arterial hypertension during pregnancy.

Effect of diuretics on sodium, potassium and chloride levels- a cross sectional study

Background: Diuretics are one of the widely used class of drugs used in various cardiovascular and other disorders. However, they can cause various metabolic adverse effects, electrolyte imbalance being among important changes.Methods: A cross sectional study was conducted in which patients diagnosed with hypertension for at least one month were included. Over a period of 6 months patients were enrolled irrespective of whether they were taking diuretics or not. Demographic details, drug therapy and electrolyte levels were recorded in a proforma. Data was analyzed for difference in serum electrolyte levels between diuretic and nondiuretic groups as well as between different diuretic groups.Results: Out of total 177 participants, 71 were on diuretic therapy. There was significant difference in mean serum sodium (S. Na), potassium (S. K) and chlorine (S. Cl) levels between diuretic and nondiuretic groups (P&lt;0.05). Hyponatremia, hypokalemia and hyperkalemia were observed. Thiazide diuretic group showed significantly greater hyponatremia compared to other diuretics (P=0.028). Hyperkalemia was observed in participants receiving K sparing diuretic or combination of loop and K sparing diuretics. Old age and number of comorbidities showed negative association with S. Na. Females had significantly more hyponatremia than male participants.Conclusions: The study confirms that diuretics cause various abnormalities in electrolytes namely Na and K levels. Old age, comorbidities and female sex are risk factors for hyponatremia.

Lung ultrasound assessment of pulmonary edema in neonates with chronic lung disease before and after diuretic therapy.

Bronchopulmonary dysplasia (BPD) is characterized by lung injury with varying degrees of disrupted alveolarization, vascular remodeling, inflammatory cell proliferation, and pulmonary edema. Diuretics are often used to ameliorate the symptoms or progression of BPD. Our primary objective was to use lung ultrasound (LUS) to determine if diuretics decrease pulmonary edema in infants with BPD. The secondary objective was to assess changes in respiratory support during the first week after initiation of diuretics. Premature infants requiring noninvasive respiratory support and starting diuretic therapy for evolving BPD were compared with a similar group of infants not receiving diuretics (control). For the diuretic group, LUS exams were performed before and on Days 1, 3, and 6 after initiation of treatment. For the control group, LUS was performed at equivalent time points. A composite pulmonary edema severity (PES) score of 0-5 was calculated based on the total number of B-lines in six scanned areas. Respiratory support parameters (FiO2 , nasal cannula flow, or CPAP) were also recorded. Infants in the diuretic (n = 28) and control (n = 23) groups were recruited at median corrected gestational ages of 34.2 (33.3-35.9) and 34.0 (33.4-36.3) weeks, respectively (p = 0.82). PES scores, FiO2 , and respiratory flow support decreased significantly from Days 0 to 6 (p < 0.0001, p = 0.001, and p = 0.01, respectively) in the diuretic group, but not in the control group. Diuretic use is associated with decreased pulmonary edema and improved oxygenation in infants with BPD during the first week of treatment.

Diuretic use before and after transcatheter aortic valve implantation: a nationwide study

Abstract Background Transcatheter aortic valve implantation (TAVI) is the new standard of care in patients of older age with symptomatic severe aortic stenosis, and these patients often depend upon diuretics for symptom relief. Randomized clinical trials suggest that approximately one third of patients undergoing TAVI do not achieve symptom relief. Furthermore, some patients have more symptoms after intervention, but “real-life” data are lacking. Purpose We examined use of diuretic therapy before and one year after TAVI in order to identify the proportion of patients who had intensification of diuretic treatment after intervention as a proxy for more symptoms. We also examined baseline factors associated with an intensification event. Methods Using Danish nationwide registries, we identified all Danish citizens who underwent TAVI from January 1, 2008 to December 31, 2019 and were alive one year after the intervention. Diuretic use pre-TAVI and 1-year post-TAVI (based on prescription fillings) was divided into the following groups: 1) no use; 2) low diuretic use: 1–40 mg of furosemide (or equivalent bumetanide); 3) intermediate diuretic use: 41–120 mg of furosemide; and 4) high diuretic use: &amp;gt;120 mg furosemide. Diuretic intensification was defined as a change from one pre-TAVI diuretic group to a higher post-TAVI diuretic group. Factors associated with intensified diuretic treatment was examined with logistic regression. In this analysis of intensification, only patients who could potentially have an intensification event were included (i.e., no diuretic use, low diuretic use, or intermediate diuretic use groups). Results A total of 3,978 patients (median age 81 [interquartile range 77–85]; 54% men) undergoing TAVI were identified. Pre-TAVI, 1,279 (32%) had no diuretic use, 1,818 (46%) had low diuretic use and 881 (22%) had intermediate diuretic use. Overall, patients with pre-TAVI intermediate diuretic use had a greater burden of cardiovascular and non-cardiovascular comorbidities (higher prevalence of heart failure, atrial fibrillation, chronic kidney disease and diabetes) compared with those with no or low diuretic use. The distribution of age and sex was similar between diuretic groups. One year post-TAVI, 1,406 (35.3%) had no diuretic use, 1,635 (41.1%) had low diuretic use, 654 (16.4%) had intermediate diuretic use and 283 (7.1%) had high diuretic use (Figure 1). Overall, 1,077 (27%) patients had intensification of diuretic treatment one year after undergoing TAVI. Ischemic heart disease and chronic renal failure were associated with an intensification event (odds ratio 1.23 [95% CI 1.05–1.23] and 1.46 [95% CI 1.10–1.94], respectively). Conclusion Among patients undergoing TAVI not treated with high-dose diuretics at time of intervention, approximately 1 out of 4 patients had intensification of diuretic treatment one year after intervention. Ischemic heart disease and chronic renal failure were associated with intensification. Funding Acknowledgement Type of funding sources: None.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and risk of depression among older people with hypertension

Background:Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), commonly used antihypertensive drugs, may have a protective effect against depression in older individuals, but evidence in humans is limited.Aims:We evaluated the risk of depression, among older individuals with hypertension, comparing ACE or ARB initiators to thiazide(-like) diuretic initiators. Thiazide(-like) diuretics were used as control because these drugs are not associated with mood disorders.Methods:We used a propensity score-matched new user cohort design with routinely collected data from general practices in England from the Clinical Practice Research Datalink database. We matched 12,938 pairs of new users of ACEIs/ARBs and thiazide(-like) diuretics with hypertension (mean age 67.6 years; 54.7% women). Follow-up time started on the date of drug initiation and ended on the date of treatment discontinuation plus 30 days, or switch to a comparator, occurrence of a study event, death, date of patient’s transfer out of practice, or end of the study period. The primary outcome was a composite endpoint of treated depression and nonfatal and fatal self-harm.Results/outcomes:Compared to the thiazide(-like) diuretic group, ACEIs/ARBs use was not associated with a lower risk of the primary outcome (hazard ratio 0.96 (95% confidence interval: 0.79; 1.15)). Results did not differ according to lipophilicity, duration of use, and average daily dose, or class (ACEIs or ARBs).Conclusions/Interpretation:New use of ACEIs or ARBs is not associated with a lower risk of depression among individuals with hypertension.

Diuretics: a contemporary pharmacological classification?

Diuretics are drugs that increase the flow of urine. They are commonly used to treat edema, hypertension, and heart failure. Typically, the pharmacological group consists of five classes: thiazide diuretics, loop diuretics, potassium-sparing diuretics, osmotic diuretics, and carbonic anhydrase inhibitors. This traditional classification and the nomenclature of diuretics have not changed over the last decades, which means that it was not adapted to current pharmacological research. Modern approaches in the field of pharmacological nomenclature suggest the introduction of mechanism-based drug class designations, which is not yet reflected in the group of diuretics. Moreover, included drug classes have lost their relevance as diuretic agents. Carbonic anhydrase inhibitors, for example, are mainly used in the treatment of glaucoma. Newer agents such as vasopressin-2 receptor antagonists or SGLT2 inhibitors possess diuretic properties but are not included in the pharmacological group. This review discusses the currentness of the pharmacological classification of diuretics. We elaborate changes in the field of nomenclature, the contemporary medical use of classical diuretics, and new diuretic agents.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00210-022-02228-0.

Tolvaptan Reduces Extracellular Fluid per Amount of Body Fluid Reduction Less Markedly than Conventional Diuretics.

Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid. We previously reported that tolvaptan efficiently reduced the intracellular fluid volume, suggesting its utility for treating cellular edema. Furthermore, tolvaptan is known for its low incidence of worsening the renal function, with conventional diuretics use associated with worsening of the renal function Methods In this retrospective observational study, five chronic kidney disease (CKD) patients with fluid retention were assessed by the bioelectrical impedance (BIA) method twice (before and after tolvaptan therapy). Tolvaptan was used with conventional diuretics. The post/pre ratio of extracellular water (ECW)/total body water (TBW) in the tolvaptan group was compared with that in 18 CKD patients undergoing body fluid reduction with conventional diuretics alone (conventional diuretics groups), taking the reduced amount of body fluid into consideration. Results Removing body fluid, either by tolvaptan or by conventional diuretics alone, decreased the ECW/TBW ratio. Of note, the reduction in extracellular fluid was milder in the tolvaptan group than in the conventional diuretics group. Conclusion Tolvaptan reduces the extracellular fluid per amount of body fluid reduction less markedly than conventional diuretics.

Profile of Drug Prescribing in Outpatient Heart Disease Patients at Mitra Medika Bondowoso Hospital

The heart is the most important organ in the body, because there are no cells and tissues that can function properly without adequate oxygen and blood supply.This study aims to determine the percentage of drug use and the number of drugs used as a reference in the process of planning and drug procurement. Sampling was determined by total sampling technique. The sample used was 279 prescriptions for outpatient heart disease at Mitra Medika Bondowoso Hospital for the period March 2021.The results of research conducted on a sample of 279 prescriptions for outpatient heart disease patients at Mitra Medika Bondowoso Hospital for the period March 2021, based on the name of the most prescribed drug, 153 prescriptions for candesartan with a percentage (14.35%), based on the number of drugs used. The most widely used was clopidogrel with a total usage of 4,231 tablets. Then based on the class of drugs the most prescribed was the diuretic group with 261 prescriptions with a percentage (24.68%), based on the strength or dose of the drug the most widely used was clopidogrel with 144 prescriptions with a percentage (13.51%).

Pharmacometabolomic study of drug response to antihypertensive medications for hypertension marker identification in Han Chinese individuals in Taiwan

Various groups of antihypertensive drugs targeting different pathways have been developed; however, the pharmacometabolic responses to these drugs have rarely been compared to elucidate the common pathway of blood pressure regulation. Here, we performed a comparative multi-dimensional pharmacometabolic study on the four major lines of antihypertensive drugs, namely angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics (DIURs), through ultra-performance liquid chromatography coupled to quantum time-of-flight mass spectrometry. Two hundred fifty patients with young-onset hypertension, who were equally divided among five study groups: non-medicated, ACEi, ARB, CCB, and DIUR groups, were recruited. In a metabolome-wide association study conducted through analysis of covariance, 37 molecular features significantly associated with pharmacometabolic responses to antihypertensive drugs were identified. One-third of these features were shared by multiple medications. ACEis, ARBs, and DIURs shared more features than CCB, partially reflecting that ACEis, ARBs, and DIURs affect the renin-angiotensin-aldosterone system. Thirteen molecular features were consistently identified by all four models of the analysis of covariance. A tandem mass spectrometry (or MS/MS) experiment was performed to decipher the chemical structure of these 13 molecular features, including ARB-associated lysophosphatidylcholine (P4135), CCB-associated diacylglycerol(15:0/18:2) (P1175), and DIUR-associated oleamide (P1516). In addition, diacylglycerol(15:0/14:2) (P408) was significantly associated with the pharmacometabolic response to all four antihypertensive drugs. The identified metabolites provide insights into the mechanisms of blood pressure regulation and potential predictive markers of pharmacometabolic responses to antihypertensive drugs.

A comparison of stone free rate between a diuretic and a control group of patients undergoing extracorporeal shock wave lithotripsy: a prospective, randomized, double-blind, placebo-controlled trial

Objectives: To compare the stone free rate and treatment success rate between a diuretic group of patients undergoing extracorporeal shock wave lithotripsy (ESWL) and a control placebo group (normal saline solution). Materials and Methods: One hundred and ninety-four patients with solitary renal calculi or ureteric calculi size of 5 mm or over were prospectively randomized into 2 groups. Ninety-seven patients in the first group (diuretic group) underwent ESWL after intravenous injection of furosemide 40 mg, and 97 patients in the second (control) group received normal saline solution 4 ml instead of furosemide prior to ESWL. The treatment protocol included 3,000 shockwaves per patient in each session with the energy beginning at 8 and progressing up to 15 kilovolts. A maximum of 3 ESWL sessions were permitted per patient. The primary outcome was stone free rate, and the secondary outcome was treatment success rate at 3 months after the first ESWL treatment. Results: The stone free rate was 48.5% compared to 50.5% for diuretic group and control group respectively and the treatment success rate was 81.4% compared to 64.9%. The difference in stone free rate was not statistically significantly different (p = 0.87), however the treatment success was, p = 0.01. Conclusion: A combination of diuretic therapy followed by ESWL improves the treatment success rate compared with standard ESWL therapy alone.

Antihypertensive drug class in combination with lipid lowering treatment for primary prevention of cardiovascular disease in the elderly

BackgroundAntihypertensives and lipid-lowering therapy (LLT) are often used concurrently. ObjectivesTo determine whether there was a difference in clinical outcomes when older patients with LLT were prescribed angiotensin-converting-enzyme-inhibitors (ACE-Is) compared with diuretics. MethodsThis analysis included 648 LLT older users free of cardiovascular disease (CVD) from a trial comparing ACE-I versus diuretic-based therapy. Comparisons were made between LLT+ACE-I (n = 335) and LLT+diuretic groups (n = 313) using multivariable Cox proportional-hazard models. Primary endpoints were all-cause and CVD mortality (in-trial [4.1-year]+post-trial [6.9-year]) and secondary endpoints (in-trial) were the composite of all-cause mortality and first CVD events and its components, CVD mortality and incident diabetes. ResultsThere were no significant differences between the two groups for the primary endpoints over the in-trial plus post-trial follow-up, nor was there a difference for any secondary outcomes over the in-trial follow-up. ConclusionsThe LLT+ACE-I and LLT+diuretic combinations showed similar effects in CVD-free older individuals. Randomised trials are needed to provide conclusive evidence.

The effects of different antihypertensive drugs on pain and joint space width of knee osteoarthritis - A comparative study with data from Osteoarthritis Initiative.

Hypertension was one common comorbidity of knee osteoarthritis (KOA), but the effect of different types of antihypertensive drugs on pain and joint space width (JSW) was unclear and not compared. Four hundred ninety KOA patients using one of the beta‐blockers, ACE inhibitors, angiotensin receptor blockers, Calcium channel blockers (CCBs), or thiazide diuretics were followed for four years. The blood pressure, cumulative knee replacement rate, Womac pain, and JSW were compared among groups. All data were from the Osteoarthritis Initiative project. The CCBs group has the highest systolic blood pressure, replacement rate, and pain score at most visit timepoints. At baseline, the CCBs group was with significantly higher pain score than the beta‐blockers group (3.3 vs 1.3, p < .05), the angiotensin receptor blockers group (3.3 vs 1.4, p < .05), and the thiazide diuretics group (3.3 vs 1.6, p < .05) in male; the CCBs group was with significantly higher pain score than the beta‐blockers group (3.8 vs 2.0, p < .01), and the angiotensin receptor blockers group (3.8 vs 2.2, p < .05) in female. The results of females at 36 months were similar to the baseline. Among the common antihypertensive drugs, CCBs were associated with high replacement rates, high pain scores, and less JSW in KOA patients.

Diuretic vs. placebo in intermediate-risk acute pulmonary embolism: a randomized clinical trial.

The role of diuretics in patients with intermediate-risk pulmonary embolism (PE) is controversial. In this multicentre, double-blind trial, we randomly assigned normotensive patients with intermediate-risk PE to receive either a single 80 mg bolus of furosemide or a placebo. Eligible patients had at least a simplified PE Severity Index (sPESI) ≥1 with right ventricular dysfunction. The primary efficacy endpoint assessed 24 h after randomization included (i) absence of oligo-anuria and (ii) normalization of all sPESI items. Safety outcomes were worsening renal function and major adverse outcomes at 48 hours defined by death, cardiac arrest, mechanical ventilation, or need of catecholamine. A total of 276 patients underwent randomization; 135 were assigned to receive the diuretic, and 141 to receive the placebo. The primary outcome occurred in 68/132 patients (51.5%) in the diuretic and in 49/132 (37.1%) in the placebo group (relative risk = 1.30, 95% confidence interval 1.04-1.61; P = 0.021). Major adverse outcome at 48 h occurred in 1 (0.8%) patients in the diuretic group and 4 patients (2.9%) in the placebo group (P = 0.19). Increase in serum creatinine level was greater in diuretic than placebo group [+4 µM/L (-2; 14) vs. -1 µM/L (-11; 6), P < 0.001]. In normotensive patients with intermediate-risk PE, a single bolus of furosemide improved the primary efficacy outcome at 24 h and maintained stable renal function. In the furosemide group, urine output increased, without a demonstrable improvement in heart rate, systolic blood pressure, or arterial oxygenation.ClinicalTrials.gov identifier NCT02268903.