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Hypertension (Dallas, Tex. : 1979) Mar 2023Decisions about hypertension management are substantially influenced by blood pressure (BP) levels measured before and soon after starting BP lowering drugs. We aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Decisions about hypertension management are substantially influenced by blood pressure (BP) levels measured before and soon after starting BP lowering drugs. We aimed to assess the utility of short-term BP changes in individuals in terms of long-term treatment response.
METHODS
Post hoc analyses of 2 randomized trials with 4-to-6 weeks active run-in for all participants, followed by randomization to active BP lowering treatment (combination perindopril±indapamide) or placebo. We categorized individuals by degree of systolic BP (SBP) change during active run-in treatment and assessed associations with subsequent postrandomization placebo-corrected BP reduction, cardiovascular events, and tolerability. We included individuals with baseline BP ≥140/90 mm Hg from the PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study; 4275 individuals with cerebrovascular disease) and ADVANCE trial (The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation; 6610 individuals with diabetes).
RESULTS
During the active run-in period, the proportion of participants with initial SBP changes in 4 categories (SBP increase, 0-9.9 mm Hg decrease, 10-19.9 mm Hg decrease, and ≥20 mm Hg decrease) were 17%, 27%, 28%, and 28% in PROGRESS and 21%, 22%, 24%, and 33% in ADVANCE. Randomization to active therapy achieved similar placebo-corrected long-term BP reductions across the 4 initial SBP change groups in both trials (-values for heterogeneity >0.1). There was no significant difference in achieving BP <140/90 mm Hg at follow-up, major cardiovascular events, nor treatment tolerability according to the SBP change during active run-in period (all -values >0.1).
CONCLUSIONS
An individual's apparent BP change immediately after commencing therapy has limited clinical utility. Therefore, more emphasis should be given to use of evidence-based regimens and measures over the long-term to ensure sustained BP control.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT00145925.
Topics: Humans; Antihypertensive Agents; Blood Pressure; Hypertension; Hypotension; Perindopril; Treatment Outcome
PubMed: 36468403
DOI: 10.1161/HYPERTENSIONAHA.122.20458 -
Journal of AOAC International May 2023Triplixam® is a new antihypertensive drug combination consisting of perindopril, amlodipine, and indapamide, which have a synergistic mechanism of action in combination...
In Vitro Dissolution Profile of Antihypertensive Mixture: Comparison Between Multivariate Methods and Statistical and Graphical Representation of Different Univariate Spectrophotometric Data.
BACKGROUND
Triplixam® is a new antihypertensive drug combination consisting of perindopril, amlodipine, and indapamide, which have a synergistic mechanism of action in combination with each other.
OBJECTIVE
Comparative study of different spectrophotometric approaches used for the simultaneous determination of perindopril, indapamide, and amlodipine in bulk powder and in dosage form Triplixam.
METHOD
The methods include univariate and multivariate spectrophotometric methods depending on either mathematical calculation or graphical representation of data. For the univariate methods: perindopril was resolved from other components using constant multiplication followed by spectrum subtraction resolution technique, and then two base point, AUC, constant value, and concentration value (CNV) methods were applied. For both amlodipine and indapamide: constant multiplication resolution technique was used, and then constant value and CNV methods were applied. CNV depends on graphical representation of data rather than statistical data. PLS and PCR chemometric assisted spectrophotometric techniques were also applied. The proposed methods are considered a green alternative to the reported methods as the greenness of the proposed methods was evaluated qualitatively and quantitatively by four green analytical evaluation tools.
RESULTS
The methods were applied for the analysis of the mixture in the pharmaceutical dosage form Triplixam and in vitro release at intestinal pH (7.4) using a USP dissolution tester.
CONCLUSIONS
The proposed green analytical methods are considered to be greener than the reported methods and simpler, so they could be used as an alternative for routine analysis of the mixture in quality control laboratories for the reason of their accurate results beside minimum manipulation steps that reduced the error and time required of the analysis with no harmful effect on analyst health as well as the environment.
HIGHLIGHTS
The study was the first in vitro dissolution profiling of perindopril, amlodipine, and indapamide. The developed methods were excellent green methods without compromising the analytical criteria.
Topics: Antihypertensive Agents; Perindopril; Indapamide; Solubility; Drug Combinations; Amlodipine
PubMed: 36420987
DOI: 10.1093/jaoacint/qsac152 -
Urologiia (Moscow, Russia : 1999) Nov 2022The outcome of surgical treatment of renal cancer depends not only on cancer-specific survival, but also on the degree of loss of renal function, which often develops...
INTRODUCTION
The outcome of surgical treatment of renal cancer depends not only on cancer-specific survival, but also on the degree of loss of renal function, which often develops after surgery, especially radical nephrectomy.
AIM
To study the features of functional changes in a solitary kidney as a compensation mechanism after radical nephrectomy for renal cancer.
MATERIALS AND METHODS
The functional state of a solitary kidney in 36 patients with renal cancer who undergone to radical nephrectomy was evaluated. There were 20 and 16 women. The mean age was 59.0+/-10.8 years (from 39 to 76 years). The size of the tumor was in the range of 7.0-12.0 cm. All patients with a solitary kidney underwent a follow-up examination 3 months after surgery, including measurement of peripheral blood pressure with calculation of mean dynamic pressure, renal ultrasound, calculation of glomerular filtration rate (GFR), renal doppler ultrasound, determination of serum fibrinogen and fibrin monomers, and microscopy of the bulbar conjunctiva. Patients who had pathological abnormalities during the examination were prescribed reno-cardioprotective drugs, including perindopril in a titrated dose, apixaban 5 mg a day as thromboprophylaxis and for improvement of the flow properties of blood for a period of 3 months with re-evaluation of the above parameters.
RESULTS
In 61.1% of patients after radical nephrectomy, on 2-4 postoperative days, there was a tendency to increase blood pressure compared to baseline values (p<0.05). By the seventh day after the procedure, the volume of the contralateral kidney increased on average by 16% (from 110.4+/-11.2 cm3 to 132.4+/-4.8 cm3, p<0.05). After radical nephrectomy, a decrease in GFR was detected in 33 cases (91.7%; p<0.05). Renal doppler ultrasound showed a moderate increase in linear blood flow, the resistance index in the main renal artery, and a decrease in the pulse index in the segmental and arcuate arteries. The microscopy of the bulbar conjunctiva in 83.3% of patients revealed changes in the microcirculatory bed, including narrowing of arterioles, dilation of venules, a decrease in venular and capillary blood flow. After 3 months of reno-cardioprotective therapy, it was revealed that the target values of blood pressure (<130/85 mm Hg) were achieved with an average dynamic blood pressure of 93.4+/-2.6 mm Hg. In addition, a decrease in creatinine to an average of 106.2+/-6.4, fibrinogen and fibrin monomers to subnormal values of 3.2+/-0.2 g/l and up to 8.1+/-0.5x10-2 g/l, respectively were seen. Renal hypertrophy according to ultrasound examination was preserved with a mean kidney volume 119.7+/-3.6 cm3. Disturbances in peripheral microcirculation according to the microscopy of the bulbar conjunctiva was assessed as moderate.
CONCLUSION
The development of CKD in patients with a solitary kidney is accompanied by a structural reorganization of the organ with an increase in blood pressure, an increase in its volume, a decrease in function, microcirculatory disorders and hypertensive nephropathy. Considering the prognostic significance of changes in the solitary kidney, it is important not only to control the functional parameters, but also to include reno- cardioprotective therapy as a standard, since it contributes to the preservation of the renal function and prevents the rapid progression of CKD. Thus, medical and social rehabilitation of patients with a solitary kidney is required. However, it is currently cannot be considered comprehensive.
Topics: Humans; Female; Middle Aged; Aged; Carcinoma, Renal Cell; Solitary Kidney; Microcirculation; Anticoagulants; Retrospective Studies; Venous Thromboembolism; Nephrectomy; Kidney Neoplasms; Kidney; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Fibrinogen; Fibrin
PubMed: 36382821
DOI: No ID Found -
High Blood Pressure & Cardiovascular... Nov 2022Hypertension represent the commonest cause of death in 2017. Hypertension is classified into two types which are primary or essential hypertension and secondary... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hypertension represent the commonest cause of death in 2017. Hypertension is classified into two types which are primary or essential hypertension and secondary hypertension. The perindopril-amlodipine combination showed a significant effect in reduction of the elevated BP and the cardiovascular complications.
AIM
To evaluate the efficacy and safety of a fixed-dose single-pill combination of perindopril-amlodipine in hypertensive patients.
METHODS
We searched PubMed, Medline, SCOPUS, and Web of Science for relevant clinical trials. Quality appraisal was evaluated according to GRADE and we assessed the risk of bias using Cochrane's risk of bias tool. We included the following outcomes: systolic blood pressure, diastolic blood pressure, pulse pressure, mean blood pressure, heart rate, cough, dizziness, headache, and peripheral edema. We performed the analysis of homogeneous data under the fixed-effects model, while analysis of heterogeneous data was analyzed under the random-effects model. We conducted a meta-regression according to the dose.
RESULTS
We included ten clinical trials. The pooled analysis showed that there was a significant reduction of the systolic blood pressure, diastolic blood pressure, pulse plessure, mean blood pressure, and heart rate after the the perindopril-amlodipine combination (MD = 18.96 [14.32, 23.60], P < 0.0001), (MD = 11.90 [8.45, 15.35], P < 0.0001), (MD = 8.44 [6.91, 9.97], P = 0.0001), (MD = 13.07 [5.86, 20.29], P = 0.0004), and (MD = 2.93 [0.89, 4.96], P = 0.005), respectively. The results of the meta-regression revealed that the efficacy is increased by increasing the dose (P < 0.001) CONCLUSION: The use of the perindopril-amlodipine combination had a significant effect on the reduction of SBP, DBP, mean blood pressure, pulse pressure, and HR.
Topics: Humans; Perindopril; Amlodipine; Antihypertensive Agents; Drug Combinations; Hypertension; Blood Pressure; Treatment Outcome
PubMed: 36287359
DOI: 10.1007/s40292-022-00544-3 -
Phytomedicine : International Journal... Jan 2023Mitochondrial dysfunction is an important pathological feature of chronic heart failure (CHF). Regulation of mitophagy can effectively maintain mitochondrial homeostasis...
BACKGROUND
Mitochondrial dysfunction is an important pathological feature of chronic heart failure (CHF). Regulation of mitophagy can effectively maintain mitochondrial homeostasis and energy metabolism, thereby inhibiting the development of CHF. Nuanxinkang (NXK), a Chinese herbal compound preparation, has significant cardioprotective effects on CHF; however, its underlying mechanism on mitophagy has not been completely clarified. This research intended to investigate the mechanism of NXK in treating myocardial infarction (MI)-induced CHF.
METHODS
The left anterior descending coronary artery (LAD) ligation surgery was performed to establish an MI-induced CHF model in male C57BL/6 mice. From 1 day after surgery, mice were given NXK (0.41, 0.82 or 1.65 g/kg/d), Perindopril (PDPL, 0.607 mg/kg/d), or an equivalent amount of sterile water by gavage for 28 continuous days. Then, mice were examined for cardiac function, myocardial fibrosis, cardiomyocyte apoptosis, mitochondrial structure and mitophagy levels of cardiomyocytes, etc. In addition, a hypoxic injury model was created using HL-1 cardiomyocytes from wild-type (WT) mice. HL-1 cells were pretreated with or without NXK-containing serum. Mitochondrial function and mitophagy levels were examined in HL-1 cells.
RESULTS
In MI-induced CHF mice, cardiac dysfunction, severe cardiac remodeling, elevated levels of oxidative stress, reduced ATP levels, and inhibition of PINK1/Parkin-mediated mitophagy were observed. High-dose NXK treatment (1.65 g/kg/d) significantly improved myocardial energy metabolism, inhibited cardiac remodeling, improved cardiac function, and restored cardiac PINK1/Parkin-mediated mitophagy levels to some extent in MI mice. In vitro, elevated levels of mitochondrial reactive oxygen species (ROS) with impaired mitochondrial membrane potential (ΔΨm) were observed in hypoxic HL-1 cells. While NXK treatment significantly protected cardiomyocytes from hypoxia-induced mitochondrial dysfunction, which is consistent with the in vivo results. Further studies showed that NXK could increase PINK1/Parkin-mediated mitophagy levels in cardiomyocytes, which could be blocked by the mitophagy inhibitor Mdivi-1.
CONCLUSION
In conclusion, NXK could prevent cardiac mitochondrial dysfunction and improve cardiac function against MI-induced CHF by promoting Pink1/Parkin-mediated mitophagy, which represents a very prospective strategy for the treatment of CHF.
Topics: Animals; Male; Mice; Heart Failure; Mice, Inbred C57BL; Mitophagy; Myocardial Infarction; Protein Kinases; Ubiquitin-Protein Ligases; Ventricular Remodeling; Drugs, Chinese Herbal
PubMed: 36279758
DOI: 10.1016/j.phymed.2022.154494 -
Frontiers in Pharmacology 2022Adverse drug reaction (ADR) is one of the leading public health concerns associated with high mortality rate. Healthcare professionals, particularly pharmacists, have a...
Adverse drug reaction (ADR) is one of the leading public health concerns associated with high mortality rate. Healthcare professionals, particularly pharmacists, have a significant role in monitoring and preventing ADRs. This study was conducted on Malaysian Pharmaceutical Society (MPS) pharmacists who worked at the hospitals, health clinics, and community pharmacies to determine if pharmacists' experiences on ADRs are still the same 10 years later. In 2010, a postal survey and in 2020, an online survey were conducted among these pharmacists. A total of 472 pharmacists and 208 participated in 2010 and 2020, respectively. About 82% and 90% of hospital/health clinic pharmacists (HCPs) observed an ADR over the last 6 months in 2010 and 2020, while 60% and 100% community pharmacists in 2010 and 2020 observed an ADR, respectively. Perindopril was the top drug (HCPs: = 0.657; CPs: = 0.98), and rash was the top ADR reported by the pharmacists in both years (HCPs: < 0.001; CPs: = 0.679). The most common actions taken by HCPs in 2010 were to report the ADR ( = 0.343), while in 2020, most HCPs explained to patients regarding the reaction ( = 0.061), which was also the same in the CP group in 2020 ( = 0.958). The top factor encouraging ADR reporting in both years and both pharmacist groups was the high degree of severity of the reaction (HCPs: < 0.001; CPs: = 0.769). While the top factors discouraging ADR reporting were a lack of information from the affected patients (HCPs: = 0.2; CPs: = 0.656), reaction is widely known (HCPs: = 0.001; CPs: = 0.144) and uncertainty of the causal relationship (HCPs: = 0.169; CPs: = 0.609). Majority of the pharmacists agreed that severe reactions should be reported (HCPs: = 0.158; CPs: = 0.501) and the main aim for reporting is to measure the incidence of ADRs (HCPs: = 0.148; CPs: = 0.762). Despite being able to identify ADRs during the daily practice, many pharmacists especially community pharmacists are not reporting them. There is a misconception on the purpose of reporting ADRs. An interventional program and ADR reporting training would be a useful step in improving ADR reporting practice.
PubMed: 36249772
DOI: 10.3389/fphar.2022.932942 -
Mayo Clinic Proceedings Oct 2022To synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).
METHODS
PubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.
RESULTS
Thirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, -0.54 [95% CI, -0.88 to -0.21]; P=.002; I=96%), IL-6 (WMD, -0.84 [95% CI, -1.03 to -0.64]; P<.001; I=0%), and TNF-α (WMD, -12.75 [95% CI, -17.20 to -8.29]; P<.001; I=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, -1.34 [95% CI, -2.65 to -0.04]; P=.04; I=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, -1.07 to -0.27]; P=.001; I=94%) and in patients with coronary artery disease (WMD, -0.75 [95% CI, -1.17 to -0.33]; P<.001; I=96%).
CONCLUSION
Based on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antihypertensive Agents; Biomarkers; C-Reactive Protein; Enalapril; Humans; Interleukin-6; Perindopril; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Tumor Necrosis Factor-alpha
PubMed: 36202494
DOI: 10.1016/j.mayocp.2022.06.036 -
Cardiovascular Drugs and Therapy Feb 2024To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy.
The Effects of a Perindopril-Based Regimen in Relation to Statin Use on the Outcomes of Patients with Vascular Disease: a Combined Analysis of the ADVANCE, EUROPA, and PROGRESS Trials.
PURPOSE
To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy.
METHODS
A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use.
RESULTS
At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77-0.98) and non-statin users (aHR 0.80, 95% CI 0.74-0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant.
CONCLUSION
Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use.
Topics: Humans; Perindopril; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Treatment Outcome; Stroke
PubMed: 36194352
DOI: 10.1007/s10557-022-07384-2 -
Saudi Pharmaceutical Journal : SPJ :... Aug 2022Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. The major challenge in managing HCC is the resistance to chemotherapy. Leptin...
UNLABELLED
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. The major challenge in managing HCC is the resistance to chemotherapy. Leptin hormone is associated with different oncogenic pathways implicated in drug resistance. Angiotensin II was found to decrease the production and secretion of leptin.
OBJECTIVE
This study investigated the potential role of an ACEI perindopril as a chemosensitizer agent to sorafenib.
METHOD
HCC was induced in mice using a single dose of diethylnitrosamine DENA (200 mg/kg) followed by phenobarbital 0.05% in drinking water for 16 weeks. Mice were then treated with perindopril (1 mg/kg/day), Sorafenib (30 mg/kg/day), or both of them for another four weeks. Leptin, VEGF, MMP-9, Cyclin D1, EpCAM, and β-catenin were measured using immunoassay while Wnt and ALDH1 were assayed using western blotting assay.
RESULTS
Perindopril whether alone or in combination with sorafenib decrease liver enzymes and preserve the liver architecture. Our study revealed that perindopril significantly increased the antineoplastic, antiangiogenic as well as anti-metastatic effects of sorafenib. This effect was correlated with the downregulation of the leptin / Wnt / β-catenin pathway and overexpression of ALDH1 while downregulation of EpCAM.
CONCLUSION
This study presents perindopril as a potential chemosensitizer agent that works through decreased expression of the leptin / Wnt / β-catenin pathway.
PubMed: 36164573
DOI: 10.1016/j.jsps.2022.06.019 -
Hypertension (Dallas, Tex. : 1979) Nov 2022The effect of 3 commonly recommended combinations of anti-hypertensive agents-amlodipine plus hydrochlorothiazide (calcium channel blocker [CCB]+thiazide), amlodipine... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The effect of 3 commonly recommended combinations of anti-hypertensive agents-amlodipine plus hydrochlorothiazide (calcium channel blocker [CCB]+thiazide), amlodipine plus perindopril (CCB+ACE [angiotensin-converting enzyme]-inhibitor), and perindopril plus hydrochlorothiazide (ACE-inhibitor+thiazide) on blood pressure variability (V) are unknown.
METHODS
We calculated the blood pressure variability (BPV) in 405 patients (130, 146, and 129 randomized to ACE-inhibitor+thiazide, CCB+thiazide, and CCB+ACE-inhibitor, respectively) who underwent ambulatory blood pressure monitoring after 6 months of treatment in the Comparisons of Three Combinations Therapies in Lowering Blood Pressure in Black Africans trial (CREOLE) of Black African patients. BPV was calculated using the SD of 30-minute interval values for 24-hour ambulatory BPs and for confirmation using the coefficient of variation. Linear mixed model regression was used to calculate mean differences in BPV between treatment arms. Within-clinic BPV was also calculated from the mean SD and coefficient of variation of 3 readings at clinic visits.
RESULTS
Baseline distributions of age, sex, and blood pressure parameters were similar across treatment groups. Participants were predominately male (62.2%) with mean age 50.4 years. Those taking CCB+thiazide had significantly reduced ambulatory systolic and diastolic BPV compared with those taking ACE-inhibitor+thiazide. The CCB+thiazide and CCB+ACE-inhibitor groups showed similar BPV. Similar patterns of BPV were apparent among groups using within-clinic blood pressures and when assessed by coefficient of variation.
CONCLUSIONS
Compared with CCB-containing combinations, ACE-inhibitor plus thiazide was associated with higher levels, generally significant, of ambulatory and within-clinic systolic and diastolic BPV. These results supplement the differential ambulatory blood pressure-lowering effects of these therapies in the CREOLE trial.
Topics: Humans; Male; Middle Aged; Perindopril; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Hypertension; Drug Therapy, Combination; Amlodipine; Hydrochlorothiazide; Calcium Channel Blockers; Drug Combinations; Thiazides; Angiotensin-Converting Enzyme Inhibitors
PubMed: 36052684
DOI: 10.1161/HYPERTENSIONAHA.121.18333