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Kardiologiia Dec 2023The 2022 draft Russian guidelines on arterial hypertension recommend initiation of antihypertensive therapy with a combination of drugs in most patients with blood...
The 2022 draft Russian guidelines on arterial hypertension recommend initiation of antihypertensive therapy with a combination of drugs in most patients with blood pressure above 150 / 90 mm Hg and / or in the presence of high-risk criteria. In 2021, the results of a 12-year analysis of the Brisighella Heart Study (BHS) were published. The aim of this study was to compare the use of different triple antihypertensive drug combinations in an Italian cohort of patients in real-life clinical practice. Combination antihypertensive therapy with a renin-angiotensin-aldosterone system inhibitor, amlodipine, and thiazide/thiazide-like diuretics provides a better blood pressure control compared to other antihypertensive drug combinations. The use of the triple combination of amlodipine/indapamide/perindopril is associated with a better metabolic profile than any other considered combination of antihypertensive drugs and a more pronounced organ-protective effect.
Topics: Humans; Antihypertensive Agents; Hypertension; Perindopril; Amlodipine; Indapamide; Blood Pressure; Drug Combinations; Thiazides
PubMed: 38088116
DOI: 10.18087/cardio.2023.11.n2582 -
European Journal of Pharmacology Jun 2024Parkinson's disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed...
Parkinson's disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed with dopamine replacement therapy using L-3, 4-dihydroxyphenylalanine (L-dopa), which is the gold standard therapy for PD. However, long-term treatment with L-dopa can lead to motor complications. The central renin-angiotensin system (RAS) is associated with the development of neurodegenerative diseases in the brain. However, the role of the RAS in dopamine replacement therapy for PD remains unclear. Here, we tested the co-treatment of the angiotensin-converting enzyme inhibitor (ACEI) with L-dopa altered L-dopa-induced dyskinesia (LID) in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Perindopril, captopril, and enalapril were used as ACEIs. The co-treatment of ACEI with L-dopa significantly decreased LID development in 6-OHDA-lesioned mice. In addition, the astrocyte and microglial transcripts involving Ccl2, C3, Cd44, and Iigp1 were reduced by co-treatment with ACEI and L-dopa in the 6-OHDA-lesioned striatum. In conclusion, co-treatment with ACEIs and L-dopa, such as perindopril, captopril, and enalapril, may mitigate the severity of L-DOPA-induced dyskinesia in a mouse model of PD.
Topics: Animals; Male; Mice; Angiotensin-Converting Enzyme Inhibitors; Antiparkinson Agents; Astrocytes; Captopril; Disease Models, Animal; Dyskinesia, Drug-Induced; Enalapril; Levodopa; Mice, Inbred C57BL; Microglia; Oxidopamine; Parkinson Disease; Perindopril
PubMed: 38642669
DOI: 10.1016/j.ejphar.2024.176573 -
Poultry Science Apr 2024At the onset of sexual maturity, the increasing circulating estrogen stimulates the formation of medullary bone, which provides available calcium for eggshell formation....
At the onset of sexual maturity, the increasing circulating estrogen stimulates the formation of medullary bone, which provides available calcium for eggshell formation. The bone loss of laying hens is caused by the continuous dynamic changes of structure bone leading to bone fragility and susceptibility. The degree of medullary bone mineralization in sexual maturity is positively correlated with bone quality in the late laying stage. This study aimed to explore the molecular regulation mechanism of bone metabolism pre- and postsexual maturity in hens based on the joint analysis of transcriptome and metabolome. A total of 50 Hy-line Sonia pullets with comparable body weight at 13 wk were selected. Eight pullets were killed at 15 wk (juvenile hens, JH) and 19 wk (laying hens, LH), and LHs were killed within 3 h after oviposition. Differentially expressed genes and metabolites in tibia were analyzed based on transcriptome and metabolome, and then combined to construct the relevant metabolisms and hub genes. In the LH hens, plasma levels of estrogen and tartrate-resistant acid phosphatase were significantly elevated by 1.7 and 1.3 times. In addition, the midpoint diameter, bone mineral density and bone mineral content of the tibia and femur were higher at 19 wk of age. A total of 580 differentially expressed genes were found between the JH and LH group in the tibia, including 280 up-regulated, and 300 down-regulated genes in the LH group. Gene set enrichment analysis (GSEA) showed that the intracellular biosynthesis and secretion of matrix vesicles were significantly enrichment in the LH hens. A total of 21 differential metabolites were identified between JH and LH group. Estradiol valerate positively correlated with L-theanine, tryptophan betaine, dopamine, and perindopril. Joint analysis showed that the top 20 hub genes were enriched in cholesterol biosynthesis and phospholipid metabolism, which played a key regulatory role in bone metabolism during pre- and postsexual maturity. These results provide a theoretical foundation for maintaining efficient egg production and reducing bone health problems in laying hens.
Topics: Female; Animals; Transcriptome; Chickens; Gene Expression Profiling; Oviposition; Estrogens
PubMed: 38417334
DOI: 10.1016/j.psj.2024.103555 -
Advances in Therapy Jan 2024The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or... (Observational Study)
Observational Study
A Retrospective Observational Real-Word Analysis of the Adherence, Healthcare Resource Consumption and Costs in Patients Treated with Bisoprolol/Perindopril as Single-Pill or Free Combination.
INTRODUCTION
The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or free-equivalent combination (FEC) of perindopril and bisoprolol (PER/BIS) in a large Italian population.
METHODS
This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or FEC between January 2017-June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as FEC (± 1 month) or SPC. Before comparing the SPC and FEC cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Drug utilization was investigated as adherence (defined by the proportion of days covered, PDC) and persistence (evaluated by Kaplan-Meier curves). Hospitalizations and mean annual direct healthcare costs (due to drug prescriptions, hospitalizations and use of outpatient services) were analyzed during follow-up.
RESULTS
The original cohort included 11,440 and 6521 patients taking the SPC and FEC PER/BIS combination, respectively. After PSM, two balanced SPC and FEC cohorts of 4688 patients were obtained (mean age 70 years, approximately 50% male, 24% in secondary prevention). The proportion of adherent patients (PDC ≥ 80%) was higher for those on SPC (45.5%) than those on FEC (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% of patients in the SPC cohort and 41.7% in the FEC cohort (p < 0.001). The SPC cohort had fewer cardiovascular (CV) hospitalizations (5.3%) than the free-combination cohort (7.4%), p < 0.001. Mean annual total healthcare costs were lower in the SPC (1999€) than in the FEC (2359€) cohort (p < 0.001).
CONCLUSION
In a real-world setting, patients treated with PER/BIS SPC showed higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on FEC of the same drugs.
Topics: Adult; Humans; Male; Aged; Female; Perindopril; Antihypertensive Agents; Hypertension; Bisoprolol; Retrospective Studies; Delivery of Health Care; Medication Adherence
PubMed: 37864626
DOI: 10.1007/s12325-023-02707-7 -
Drug Development Research Jun 2024As a hybrid weapon, two novel series of pyrazoles, 16a-f and 17a-f, targeting both COX-2 and ACE-1-N-domain, were created and their anti-inflammatory, anti-hypertensive,...
Vicinal diaryl pyrazole with tetrazole/urea scaffolds as selective angiotensin converting enzyme-1/cyclooxygenase-2 inhibitors: Design, synthesis, anti-hypertensive, anti-fibrotic, and anti-inflammatory.
As a hybrid weapon, two novel series of pyrazoles, 16a-f and 17a-f, targeting both COX-2 and ACE-1-N-domain, were created and their anti-inflammatory, anti-hypertensive, and anti-fibrotic properties were evaluated. In vitro, 17b and 17f showed COX-2 selectivity (SI = 534.22 and 491.90, respectively) compared to celecoxib (SI = 326.66) and NF-κB (IC 1.87 and 2.03 μM, respectively). 17b (IC 0.078 μM) and 17 f (IC 0.094 μM) inhibited ACE-1 comparable to perindopril (PER) (IC 0.048 μM). In vivo, 17b decreased systolic blood pressure by 18.6%, 17b and 17f increased serum NO levels by 345.8%, and 183.2%, respectively, increased eNOS expression by 0.97 and 0.52 folds, respectively and reduced NF-κB-p65 and P38-MAPK expression by -0.62, -0.22, -0.53, and -0.24 folds, respectively compared to l-NAME (-0.34, -0.45 folds decline in NF-κB-p65 and P38-MAPK, respectively). 17b reduced ANG-II expression which significantly reversed the cardiac histological changes induced by L-NAME.
Topics: Pyrazoles; Animals; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Tetrazoles; Anti-Inflammatory Agents; Cyclooxygenase 2 Inhibitors; Rats; Drug Design; Male; Antifibrotic Agents; Cyclooxygenase 2; Blood Pressure; Humans; Peptidyl-Dipeptidase A
PubMed: 38845214
DOI: 10.1002/ddr.22217 -
Journal of Chromatography. A Aug 2024Universal microchip isotachophoresis (μITP) methods were developed for the determination of cationic and anionic macrocomponents (active pharmaceutical ingredients and...
Universal microchip isotachophoresis (μITP) methods were developed for the determination of cationic and anionic macrocomponents (active pharmaceutical ingredients and counterions) in cardiovascular drugs marketed in salt form, amlodipine besylate and perindopril erbumine. The developed methods are characterized by low reagent and sample consumption, waste production and energy consumption, require only minimal sample preparation and provide fast analysis. The greenness of the proposed methods was assessed using AGREE. An internal standard addition was used to improve the quantitative parameters of μITP. The proposed methods were validated according to the ICH guideline. Linearity, precision, accuracy and specificity were evaluated for each of the studied analytes and all set validation criteria were met. Good linearity was observed in the presence of matrix and in the absence of matrix, with a correlation coefficient of at least 0.9993. The developed methods allowed precise and accurate determination of the studied analytes, the RSD of the quantitative and qualitative parameters were less than 1.5% and the recoveries ranged from 98 to 102%. The developed μITP methods were successfully applied to the determination of cationic and anionic macrocomponents in six commercially available pharmaceutical formulations.
Topics: Isotachophoresis; Amlodipine; Reproducibility of Results; Green Chemistry Technology; Quality Control; Pharmaceutical Preparations; Perindopril; Limit of Detection; Electrophoresis, Microchip; Cardiovascular Agents
PubMed: 38852265
DOI: 10.1016/j.chroma.2024.465055 -
Journal of Hypertension Aug 2024Limited data exist on the relationship between declining kidney function and cardiovascular events, dementia, and mortality in patients with a history of stroke.Thus the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Limited data exist on the relationship between declining kidney function and cardiovascular events, dementia, and mortality in patients with a history of stroke.Thus the aims of the study were to investigate functional relationships between dynamic kidney function change and cardiovascular outcomes, and clarify whether adding kidney parameters to conventional cardiovascular risk factors improves model discrimination.
METHODS
Post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) clinical trial of blood pressure lowering for the secondary prevention of stroke. We examined the association between dynamic kidney function defined as percentage change (declines of >30%, and >0 to ≤30%, and increases of ≥0 to <30%, and ≥30%) in estimated glomerular filtration rate (eGFR) over 2 years and recurrent stroke, major cardiovascular events, dementia and all-cause death over the next 2 years using Cox proportional hazard models controlling for eGFR at registration and potential confounders. Restricted cubic splines were used to assess the functional relationships. C-statistics and Net Reclassification Improvement (NRI) at 2 years were used to assess model discrimination.
RESULTS
In 4591 patients followed for a mean of approximately 2 years, 254 (5.5%) developed recurrent stroke, 391 (8.5%) had a major cardiovascular event, 221 (4.8%) developed dementia, and 271 (5.9%) died. Reverse J-like or U-like relationships were observed for percent declines in eGFR and outcomes. Using declines in eGFR of >0 to ≤30% as a reference, increased risks were evident for a greater decline (>30%) in relation to recurrent stroke [adjusted hazard ratio 1.85, 95% confidence interval (CI) 1.20-2.85], major cardiovascular event (2.24, 1.62-3.10) and all-cause death (2.09, 1.39-3.15). A larger increase (≥30%) in eGFR was also associated with a greater risk of all-cause death (1.96, 1.14-3.37). Improvements in the C-statistic were found by adding baseline eGFR and percent change compared with a model with conventional cardiovascular risk factors alone, for major cardiovascular events, dementia, and all-cause mortality.
CONCLUSION
Declining kidney function following an incident cerebrovascular event is associated with additional risk of a major cardiovascular events, dementia, and 2-year mortality. However, a large increase in kidney function was also found to be associated with a higher risk of mortality.
Topics: Humans; Stroke; Perindopril; Male; Female; Dementia; Aged; Middle Aged; Glomerular Filtration Rate; Recurrence; Risk Factors; Kidney
PubMed: 38690898
DOI: 10.1097/HJH.0000000000003711 -
Diabetes, Metabolic Syndrome and... 2024This study aimed to investigate the intervention mechanism of Jiawei Shengjiangsan (JWSJS) on kidney injury in diabetic nephropathy mice.
PURPOSE
This study aimed to investigate the intervention mechanism of Jiawei Shengjiangsan (JWSJS) on kidney injury in diabetic nephropathy mice.
METHODS
Thirty 8-week-old db/db mice were randomly divided into five groups: model group, Perindopril group, and JWSJS low-, medium-, and high-dose groups (n=6 per group) based on body weight. Additionally, a blank control group was established consisting of 6 db/m mice aged 8 weeks. The blank and model groups received daily intragastric administration of 7g/kg/d pure water. The remaining groups were assigned to JWSJS low (3.5g/kg/d), medium (7g/kg/d), high (14g/kg/d) dosage groups, and perindopril positive control group (0.48mg/kg/d) for 12 weeks. Post-experiment, serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed using an automatic biochemical analyzer. Enzyme-linked immunosorbent assay (ELISA) measured 24-hour urinary albumin, neutrophil gelatinase-associated lipocalin (NGAL), TNF-α, IL-1β, VCAM-1, MCP-1, and HbA1c. Western blot assessed the protein expressions of p-PI3K, p-Akt, and p-NF-κB p65, while pathological kidney changes were observed.
RESULTS
Compared to the blank group, the model group exhibited increased SCr, BUN, 24-hour urinary albumin, serum NGAL, TNF-α, IL-1β, VCAM-1, MCP-1, HbA1c, p-PI3K, and p-Akt, alongside increased p-NF-κB p65 expression, indicating significant kidney pathology. After treatment, the JWSJS group showed decreased SCr, BUN, 24-hour urinary microalbumin, NGAL, HbA1c, TNF-α, IL-1β, VCAM-1, MCP-1 levels, increased p-PI3K and p-Akt expression (P<0.05), and reduced p-NF-κB p65 content (P<0.05). Histopathological analysis revealed that JWSJS ameliorated renal tubular epithelial cell damage, glomerular capillary and basement membrane injuries, and facilitated the repair of damaged podocytes in diabetic nephropathy mice.
CONCLUSION
JWSJS demonstrated efficacy in reducing renal inflammation in diabetic nephropathy mice, with its mechanism likely associated with the inhibition of the PI3K/Akt/NF-κB signaling pathway.
PubMed: 38629025
DOI: 10.2147/DMSO.S456205 -
World Journal of Clinical Cases Jun 2024Current treatments for chronic heart failure (CHF) are therapeutically ineffective. The optimization of treatments for this disease needs to be explored and analyzed.
BACKGROUND
Current treatments for chronic heart failure (CHF) are therapeutically ineffective. The optimization of treatments for this disease needs to be explored and analyzed.
AIM
To analyze the effect of using Luhong Formula in the cardiac rehabilitation of patients with CHF and its influence on cardiopulmonary function (CPF) and prognosis.
METHODS
In total, 160 patients with CHF admitted between June 2022 and June 2023 were selected, including 75 receiving perindopril (control group) and 85 receiving Luhong Formula (research group). We conducted comparative analyses on the curative effects of traditional Chinese medicine (TCM) syndromes and cardiac function, CPF [oxygen consumption at the anaerobic threshold (VO AT) and at peak exercise (peak VO)], echocardiographic indexes [left atrial volume index (LAVI), left ventricular muscle mass index (LVMI), left ventricular ejection fraction (LVEF)], and prognosis [major adverse cardiovascular events (MACEs) at 6 months follow-up].
RESULTS
The research group showed markedly higher curative effects of TCM syndromes and cardiac function than the control group. In addition, post-treatment VO AT, peak VO, LVMI and LVEF in the research group were significantly higher, whereas LAVI was significantly lower, than those of the control group. Furthermore, fewer patients in the research group developed MACEs at the 6-month follow-up.
CONCLUSION
Luhong Formula is more therapeutically effective than perindopril for the cardiac rehabilitation of patients with CHF, specifically in enhancing CPF and prognosis.
PubMed: 38898832
DOI: 10.12998/wjcc.v12.i17.3027 -
Revista Espanola de Anestesiologia Y... Nov 2023Angioedema is a potentially life-threatening condition due to the risk of airway compromise leading to deterioration of respiratory function, hypoxia, and ultimately,...
Angioedema is a potentially life-threatening condition due to the risk of airway compromise leading to deterioration of respiratory function, hypoxia, and ultimately, cardiopulmonary arrest. It can be either unprovoked or triggered by pharmaceutical agents, emotional or physiologic factors, upper airway trauma, or surgical stress. A 46-year-old man previously prescribed perindopril developed angioedema of the tongue 4 h after being discharged from the Post Anesthesia Care Unit (PACU). A multidisciplinary team was called and they outlined an airway management strategy to use in the event of worsening. The strategy consisted of either fiberoptic intubation by an anesthesiologist or surgical tracheostomy performed by the surgical team, both performed with the patient awake and in spontaneous ventilation. The aim of this case report is to raise awareness that angioedema is a potentially life-threatening condition. For optimal management, it is important to prepare in advance a detailed airway management strategy to be implemented by a multidisciplinary team.
Topics: Male; Humans; Middle Aged; Angiotensin-Converting Enzyme Inhibitors; Angioedema; Airway Management; Tongue
PubMed: 37678466
DOI: 10.1016/j.redare.2022.10.011