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Advances in Therapy Jun 2021Combination antihypertensive therapy is required by most patients to achieve guideline-recommended blood pressure (BP) goals. This study assessed the effectiveness and... (Observational Study)
Observational Study
Effectiveness and Tolerability of the Single-Pill Combination of Bisoprolol and Perindopril in Patients with Arterial Hypertension and Stable Coronary Artery Disease in Daily Clinical Practice: The STYLE Study.
INTRODUCTION
Combination antihypertensive therapy is required by most patients to achieve guideline-recommended blood pressure (BP) goals. This study assessed the effectiveness and tolerability of bisoprolol/perindopril (Bis/Per) single-pill combination (SPC) in Russian patients with hypertension and coronary artery disease (CAD) treated in routine clinical practice.
METHODS
STYLE (NCT03730116) was an open-label, uncontrolled, prospective observational study conducted in patients who were already receiving Bis/Per SPC, switched to SPC from Bis or Per monotherapy, or switched from a free combination of Bis and Per. Primary endpoint criteria were assessed at 1 and 3 months and included change in mean office systolic/diastolic blood pressure (SBP/DBP), proportion achieving target BP (< 140/90 mmHg), and measures of antianginal effectiveness.
RESULTS
The full analysis set comprised 1892 subjects. Mean age was 61.9 ± 8.8 years, 53.2% were women, and mean durations of hypertension and CAD were 12.5 ± 7.9 and 7.2 ± 6.4 years, respectively. Mean SBP/DBP decreased by 22.3/11.0 mmHg and 31.5/15.9 mmHg at 1 and 3 months, respectively (P < 0.0001 vs baseline). Target BP was achieved by 49.2% and 86.7% of patients at 1 and 3 months, respectively. Reductions in mean number of angina attacks and nitrate consumption and improvements in heart rate were statistically significant. Treatment was well tolerated.
CONCLUSION
Treatment of patients with hypertension and CAD with Bis/Per SPC for 3 months was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by an improvement in angina symptoms. Treatment was well tolerated in a broad patient population representative of those seen in everyday clinical practice.
Topics: Aged; Antihypertensive Agents; Bisoprolol; Blood Pressure; Coronary Artery Disease; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Perindopril; Russia; Treatment Outcome
PubMed: 33991323
DOI: 10.1007/s12325-021-01754-2 -
Pharmaceutical Development and... 2015Perindopril erbumine (PE) is a BCS (Biopharmaceutics Classification System) class 3 drug with high solubility and low permeability. It is an inhibitor of the enzyme that... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Perindopril erbumine (PE) is a BCS (Biopharmaceutics Classification System) class 3 drug with high solubility and low permeability. It is an inhibitor of the enzyme that converts angiotensin I (Angiotensin Converting Enzyme, ACE) into angiotensin II as well as causing the degradation of the vasodilator bradykinin into an inactive heptapeptide. The aim of this study was to develop an alternative drug product by using a different salt of perindopril and to evaluate the bioequivalence between PE, not still licensed, and perindopril arginine (PA), licensed in many countries, and to prepare PE tablets by using direct compression method. Many different formulations were prepared, among which F3-coded formulation was only selected due to releasing of 98.03% active substance at 45th minute. Bioequivalence study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study and conducted in 24 male healthy volunteers via peroral route. The results of bioequivalence study were evaluated for Perindopril and Perindoprilat according to Cmax, tmax and AUC criteria. The geometric mean ratios (90% CI) of perindopril and perindoprilat followed test and reference drug were calculated for AUC0-t and Cmax, 105.946% (100.218-112.002%) and 110.437% (102.534-118.948%); 109.542% (98.364-121.992%) and 115.729% (101.031-132.565%), respectively. The 90% confidence intervals of them were found within the standard bioequivalence range (80-125%).
Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cross-Over Studies; Drug Liberation; Humans; Male; Middle Aged; Perindopril; Salts; Solubility; Tablets; Therapeutic Equivalency; Young Adult
PubMed: 24799074
DOI: 10.3109/10837450.2014.915568 -
Diabetes Therapy : Research, Treatment... Jul 2022Cardiovascular disease (CVD) is a leading cause of death globally, driven by the high rates of risk factors, such as diabetes and hypertension. As the prevalence of... (Review)
Review
Cardiovascular disease (CVD) is a leading cause of death globally, driven by the high rates of risk factors, such as diabetes and hypertension. As the prevalence of these risk factors is particularly high in the Gulf region, better diagnosis and management of type 2 diabetes (T2D) and hypertension has the potential to dramatically reduce adverse cardiovascular outcomes for individuals in that part of the world. This article provides a summary of presentations made during the EVIDENT summit, a virtual symposium on Evidence in Diabetes and Hypertension, held in September 2021, including a review of the various guidelines for both T2D and hypertension, as well as recent findings relevant to the safety and efficacy for therapies relating to these conditions. Of relevance to the Gulf region, the risk of hypoglycaemia with sulfonylureas during Ramadan was reviewed. For the management of T2D, sulfonylureas have been a long-standing medication used to achieve glycaemic control; however, differences have emerged between early and later generations, with recent studies suggesting improvements in the safety profiles of late-generation sulfonylureas. For patients with hypertension, incremental therapy changes are recommended to reduce the risk of cardiovascular complications that are associated with increasing blood pressure. For first-line therapy, angiotensin-converting enzyme inhibitors (ACEi), such as perindopril, have been demonstrated to reduce the risk of cardiovascular and all-cause mortality. The addition of calcium channel blockers and diuretics to ACEi has been shown to be effective in patients with poorly controlled hypertension. The different renin-angiotensin-aldosterone system inhibitors are reviewed, and the benefit of combination therapies, including amlodipine and indapamide in patients with difficult-to-control hypertension, is investigated. The benefits of lifestyle modifications for these patients are also discussed, with important clinical considerations that are expected to inform patient management in daily clinical practice.
PubMed: 35679010
DOI: 10.1007/s13300-022-01282-4 -
Metabolism: Clinical and Experimental Oct 2016Apoptosis contributes nephropathy pathogenesis in diabetes. However, its mechanisms still remain unclear. We examined the extent to which the angiotensin-II type 1...
BACKGROUND
Apoptosis contributes nephropathy pathogenesis in diabetes. However, its mechanisms still remain unclear. We examined the extent to which the angiotensin-II type 1 receptor blocker (AT1RB) irbesartan and the angiotensin converting enzyme inhibitor (ACEI) perindopril affected the apoptosis-related proteins Bcl-2, Bax, caspase-3, cytochrome-c and Ku70 in streptozotocin (STZ)-diabetic rats.
MATERIALS AND METHODS
Animals were divided into five groups of eight each, four of which received STZ (60mg/kg in a single dose, i.p.) to induce diabetes. The groups were performed as untreated diabetic; non-diabetic control; daily irbesartan (15mg/kg/day) or perindopril (6mg/kg/day) and also combined irbesartan and perindopril (respectively, 5mg/kg/day, 3mg/kg/day) were applied by gavage for 30days to STZ-diabetic rats. The kidney tissue analysis was performed by using immunohistochemical staining with Bcl-2, Bax, caspase-3, cytochrome-c and Ku70 antibodies and by using Western blot analysis with caspase-3 and cytochrome-c antibodies.
RESULTS
Immunoreactivity of Bax, caspase-3, cytochrome-c and Ku70 was increased in the tubuli and glomeruli of the untreated diabetic group, but decreased in all treated diabetic groups. In the irbesartan and perindopril treated diabetic groups Bcl-2 immunoreactivity was higher than that of the untreated diabetic group. Caspase-3 and cytoplasmic cytochrome-c protein levels increased in the untreated diabetic group.
CONCLUSIONS
We conclude that the increased expression of Bax and caspase-3, and the increased level of cytoplasmic cytochrome-c relate to renal tissue injury. This case is also seen in the early stages of diabetes as a result of the damage caused by local increased expression of renin angiotensin system (RAS) in the renal tissue, which is induced by hyperglycemia. The increase of the cytosolic cytochrome-c, caspase-3 and Ku70 expression in the tubuli is suggestive of apoptosis. Overall, our results show that treatments of irbesartan and perindopril are effective and efficient in preventing renal tissue injury and apoptosis by blocking the RAS in experimental diabetic nephropathy and reducing the expression of proteins associated with apoptosis.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis Regulatory Proteins; Biphenyl Compounds; Blood Glucose; Caspase 3; Cytochromes c; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Irbesartan; Kidney; Kidney Glomerulus; Kidney Tubules; Ku Autoantigen; Male; Perindopril; Rats; Rats, Wistar; Tetrazoles; bcl-2-Associated X Protein
PubMed: 27621182
DOI: 10.1016/j.metabol.2016.06.010 -
Journal of AOAC International Sep 2023Antihypertensives bisoprolol fumarate (BIS) and perindopril arginine (PER) were simultaneously determined in their pure, bulk, and combined tablet dosage form. (Comparative Study)
Comparative Study
Chromatographic Techniques for Assessment of Bisoprolol Fumarate and Perindopril Arginine in Solid Formulations under Various Stress Conditions and Application to Six Sigma, Content Uniformity, and Comparative Dissolution Approaches.
BACKGROUND
Antihypertensives bisoprolol fumarate (BIS) and perindopril arginine (PER) were simultaneously determined in their pure, bulk, and combined tablet dosage form.
OBJECTIVE
This study develops a novel, reproducible, and accurate Reversed phase high-performance liquid chromatography (RP-HPLC) and Reversed phase ultra-performance liquid chromatography (RP-UPLC) with photodiode array detection techniques, which were then applied to in vitro dissolution studies.
METHODS
The first RP-HPLC method relied on isocratic elution using a mobile phase of methanol-0.05 M phosphate buffer pH 2.6 (1 + 1, by volume), and separation was performed using a Thermo Hypersil C8 column (150 mm × 4.6 mm, 5 μm). Ion-pair UPLC was the second method. An acceptable resolution was achieved using an RP-C18 chromatographic column, Agilent Eclipse (100 × 2.1 mm, 1.7 μm), with a mobile phase containing 0.005 M sodium 1-heptane sulfonate-triethylamine (64 + 1 + 35, by volume), adjusted with phosphoric acid to a pH of 2.0. RP-HPLC used a 1.0 mL/min flow rate, while UPLC used 0.5 mL/min, and the two methods used detection at 210 nm.
RESULTS
Calibration curves of BIS and PER were linear for RP-HPLC and RP-UPLC methods at 0.5-15 and 0.5-40 μg/mL, respectively. BIS and PER had RP-UPLC LODs of 0.22 and 0.10 μg/mL, respectively, and LOQs of 0.68 and 0.31 μg/mL, respectively. As a result, the approach has been effectively applied to in vitro dissolution testing for drugs in generic and reference products, showing that the two products are comparable. The Six Sigma approach was implemented to compare the recommended and United States Pharmacopeia (USP) procedures, which both exhibited process capability index (Cpk) >1.33. A content uniformity test demonstrated that the drugs in their dosage form met the acceptance limit (85-115%). The degradation products were reliably distinguished from pure drugs for a range of retention times.
CONCLUSION
In their commercial drug product, the proposed method could be used in QC laboratories for concurrent testing, content uniformity, and in vitro dissolution investigations of BIS and PER. The methods were successfully validated per International Council for Harmonisation (ICH) guidelines.
HIGHLIGHTS
This study is innovative since it is the first to establish and validate specific and reproducible UPLC and HPLC methods for the concurrent quantitation of the studied drugs in their binary mixture and application to lean Six Sigma, content uniformity, and comparative dissolution approaches.
Topics: Arginine; Bisoprolol; Perindopril; Solubility; Total Quality Management
PubMed: 37341634
DOI: 10.1093/jaoacint/qsad077 -
The Medical Letter on Drugs and... Jun 2021
Topics: Cardiovascular Agents; Chronic Disease; Heart Failure; Humans; Recovery of Function; Stroke Volume; Treatment Outcome; Ventricular Function, Left
PubMed: 34181629
DOI: No ID Found -
Expert Opinion on Drug Safety Dec 2020ACE-inhibitors (ACEI) and diuretics are the typical first-line antihypertensive drugs with complementary mechanisms of action. The present paper is summarizing the... (Comparative Study)
Comparative Study Review
INTRODUCTION
ACE-inhibitors (ACEI) and diuretics are the typical first-line antihypertensive drugs with complementary mechanisms of action. The present paper is summarizing the evidence supporting the efficacy of their combination in a broad range of hypertensive patients.
AREAS COVERED
This source of data is different trials investigating the use of ACEI and diuretics in different populations of patients. The available evidence supports some advantage for thiazide-type compounds (chlortalidone-CHT and indapamide-IND) in the prevention of major CV complications. In terms of safety, hydrochlorothiazide (HCTZ) and indapamide are associated with a lesser rate of hypokalemia and abnormalities of metabolic profile (glucose control, uric acid levels, serum potassium levels). As far as the results of clinical trials, the most relevant studies are involving the combination of benazepril or perindopril with HCTZ (benazepril) or IND (Perindopril) respectively. All these studies have resulted in a favorable clinical outcome. In terms of safety profile, the combination of ACEi and diuretic is safe and comparable with that of ACEi and calcium channel blockers with no differences in the rate of major adverse events (cough or angioedema) and a lower rate of ankle edema.
EXPERT OPINION
The combination of ACEi and diuretic is safe and well-tolerated and should be considered among the first-line treatments in most of the patients with hypertension.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Thiazides
PubMed: 33047990
DOI: 10.1080/14740338.2020.1836151 -
Frontiers in Physiology 2023Angiogenesis is an important exercise-induced response to improve blood flow and decrease vascular resistance in spontaneously hypertensive rats (SHR), but some...
Angiogenesis is an important exercise-induced response to improve blood flow and decrease vascular resistance in spontaneously hypertensive rats (SHR), but some antihypertensive drugs attenuate this effect. This study compared the effects of captopril and perindopril on exercise-induced cardiac and skeletal muscle angiogenesis. Forty-eight Wistar rats and 48 SHR underwent 60 days of aerobic training or were kept sedentary. During the last 45 days, rats were treated with captopril, perindopril or water (Control). Blood pressure (BP) measurements were taken and histological samples from the tibialis anterior (TA) and left ventricle (LV) muscles were analyzed for capillary density (CD) and vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS) protein level. Exercise increased vessel density in Wistar rats due to higher VEGFR-2 (+17%) and eNOS (+31%) protein level. Captopril and perindopril attenuated exercise-induced angiogenesis in Wistar rats, but the attenuation was small in the perindopril group, and this response was mediated by higher eNOS levels in the Per group compared to the Cap group. Exercise increased myocardial CD in Wistar rats in all groups and treatment did not attenuate it. Both exercise and pharmacological treatment reduced BP of SHR similarly. Rarefaction was found in TA of SHR compared to Wistar, due to lower levels of VEGF (-26%) and eNOS (-27%) and treatment did not avoid this response. Exercise prevented these reductions in control SHR. While rats treated with perindopril showed angiogenesis in the TA muscle after training, those rats treated with captopril showed attenuated angiogenesis (-18%). This response was also mediated by lower eNOS levels in Cap group compared with Per and control group. Myocardial CD was reduced in all sedentary hypertensive compared with Wistar and training restored the number of vessels compared with sedentary SHR. In conclusion, taken into account only the aspect of vessel growth, since both pharmacological treatments reduced BP in SHR, the result of the present study suggests that perindopril could be a drug of choice over captopril for hypertensive practitioners of aerobic physical exercises, especially considering that it does not attenuate angiogenesis induced by aerobic physical training in skeletal and cardiac muscles.
PubMed: 37284543
DOI: 10.3389/fphys.2023.1147525 -
Cardiovascular Drugs and Therapy Apr 2017Inhibition of the renin-angiotensin system (RAS) is beneficial in patient management after myocardial infarction (MI). However, whether RAS inhibition also provides...
PURPOSE
Inhibition of the renin-angiotensin system (RAS) is beneficial in patient management after myocardial infarction (MI). However, whether RAS inhibition also provides cardiac protection in the acute phase of MI is unclear.
METHODS
Male 129sv mice underwent coronary artery occlusion to induce MI, followed by treatment with losartan (L, 20 and 60 mg/kg), perindopril (P, 2 and 6 mg/kg), amlodipine (20 mg/kg as a BP-lowering agent) or vehicle as control. Drug effects on hemodynamics were examined. Effects of treatments on incidence of cardiac rupture, haematological profile, monocyte and neutrophil population in the spleen and the heart, cardiac leukocyte density, expression of inflammatory genes and activity of MMPs were studied after MI.
RESULTS
Incidence of cardiac rupture within 2 weeks was significantly and similarly reduced by both losartan (L) and perindopril (P) in a dose-dependent manner [75% (27/36) in vehicle, 40-45% in low-dose (L 10/22, P 8/20) and 16-20% (L 5/32, P 4/20) in high-dose groups, all P < 0.05]. This action was independent of their BP-lowering action, as amlodipine reduced BP to a similar degree without effect on rupture (70%, 21/30). Compared to the control group, high dose losartan and perindopril decreased counts of white blood cells, neutrophils and lymphocytes (all P < 0.05), and inhibited splenic monocyte and neutrophil release into the circulation. Consequently, monocyte, neutrophil and leukocyte infiltration, inflammatory gene expressions (IL-1β, IL-6, MMP9, MCP-1, TNF-α and TGFβ1) and activity of MMP2 and MMP9 in the infarct tissue were attenuated by losartan and/or perindopril treatment (all P < 0.05).
CONCLUSIONS
RAS inhibition by losartan or perindopril prevented cardiac rupture at the acute phase of MI through blockade of splenic release of monocytes and neutrophils and consequently attenuation of systemic and regional inflammatory responses.
Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Chemotaxis, Leukocyte; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Rupture, Post-Infarction; Inflammation; Inflammation Mediators; Losartan; Male; Mice, 129 Strain; Monocytes; Myocardial Infarction; Myocardium; Neutrophil Infiltration; Neutrophils; Perindopril; Renin-Angiotensin System; Spleen; Time Factors
PubMed: 28204966
DOI: 10.1007/s10557-017-6717-2 -
European Review For Medical and... Aug 2019To explore the anti-apoptotic effect of perindopril on myocardial cells in mice with acute myocardial infarction (AMI).
OBJECTIVE
To explore the anti-apoptotic effect of perindopril on myocardial cells in mice with acute myocardial infarction (AMI).
MATERIALS AND METHODS
A total of 48 mice were randomly divided into 4 groups before intervention, namely sham operation group (Sham group, n=12), AMI group (n=12), 1.5 mg/kg perindopril treatment group (Perindopril group, n=12), and 1.5 mg/kg perindopril treatment and Toll-like receptor-4 (TLR4) knockout group (TLR4-/-Perindopril group, n=12). Mice in the control group and AMI group were gavaged with normal saline, and those in the Perindopril group and TLR4-/-Perindopril group were gavaged with perindopril for 7 d. On the 4th day after drug administration, mice in the AMI group, Perindopril group and TLR4-/-Perindopril group were subjected to the ligation of the anterior descending coronary artery to induce AMI, and those in the Sham group underwent the same operation, but had a loose knot at the anterior descending coronary artery. At 24 h after the above operation, color echocardiography was performed on mice to observe changes in cardiac function. Then, the mice were sacrificed. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) assay was carried out to determine myocardial apoptosis. Immunohistochemistry and Western blotting technique were employed to detect the protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p50 in infarction zones. The messenger ribonucleic acid (mRNA) expression levels of TLR4 and NF-κB p50 in infarction zones were measured via Reverse Transcription-Polymerase Chain Reaction (RT-PCR).
RESULTS
Perindopril could significantly reduce the number of apoptotic myocardial cells after AMI. Mouse echocardiography showed that ejection fraction (EF), left ventricular fractional shortening (FS), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) of AMI mice in the Perindopril groups were markedly superior to those in the AMI group. AMI mice in the Perindopril group had decreased expression levels of Bax protein and TLR4 and NF-κB p50 mRNA and protein, as well as the Bax/Bcl-2 ratio. Knockout of TLR4 attenuated the effect of perindopril in alleviating myocardial apoptosis after AMI.
CONCLUSIONS
Perindopril inhibits myocardial apoptosis in mice with AMI through the TLR4/NF-κB pathway.
Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Animals; Apoptosis; Disease Models, Animal; Echocardiography; Heart Ventricles; Humans; Mice; Mice, Knockout; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; NF-kappa B; Perindopril; Stroke Volume; Toll-Like Receptor 4; Ventricular Function, Left
PubMed: 31378910
DOI: 10.26355/eurrev_201908_18558