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Journal of the... Jun 2002The rationale for using angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) in combination with thiazide diuretic therapy has... (Review)
Review
The rationale for using angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) in combination with thiazide diuretic therapy has centred formerly around antihypertensive synergy and counter-balancing adverse metabolic effects, particularly on potassium homeostasis. However, two recent landmark clinical trials that included high-risk hypertensive patients have now provided an evidence base for this form of combination therapy by demonstrating the efficacy of perindopril/indapamide and losartan/ hydrochlorothiazide in reducing vascular morbidity and mortality, a proportion of the benefit being unaccounted for by blood pressure reduction alone. Several unresolved issues remain concerning class effects versus specific drug effects, optimal dosing, potential differences in efficacy between ACE-I and ARBs, whether elderly mild hypertensives benefit from this form of combination therapy, and the possibility that the optimal regimen may be a triple combination of ACE-I, ARB and thiazide diuretic. These issues will be resolved by ongoing and future major endpoint trials in hypertension.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Renin-Angiotensin System
PubMed: 12228846
DOI: 10.3317/jraas.2002.021 -
Diabetes & Vascular Disease Research Sep 2007Impaired insulin sensitivity and hypertension are risk factors for atherosclerosis, which in turn leads to a variety of cardiovascular diseases. In both conditions, the... (Review)
Review
Impaired insulin sensitivity and hypertension are risk factors for atherosclerosis, which in turn leads to a variety of cardiovascular diseases. In both conditions, the risks of morbidity and mortality appear to be further increased. Impaired insulin sensitivity is also a precursor for diabetes. The renin-angiotensin-aldosterone system (RAAS) is implicated in the development of both hypertension and insulin resistance. Antihypertensive agents that act by blocking the RAAS, such as angiotensin-converting enzyme (ACE) inhibitors, may improve insulin sensitivity and therefore prevent the deleterious consequences of insulin resistance, including type 2 diabetes. ACE inhibitors appear to improve insulin sensitivity in patients with hypertension and insulin resistance, including diabetes. This review assesses the literature surrounding the use of the ACE inhibitor perindopril in patients with hypertension and varying degrees of insulin resistance, including the effects of perindopril in preventing the development of diabetes and subsequent cardiovascular morbidity and mortality.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Diabetes Mellitus, Type 2; Humans; Hypertension; Insulin Resistance; Models, Biological; Perindopril
PubMed: 17907106
DOI: 10.3132/dvdr.2007.037 -
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 -
CJC Open Sep 2021Hypertension is a risk factor for the development and exacerbation of atrial fibrillation (AF). Angiotensin-converting enzyme inhibitors are a standard-of-care treatment...
BACKGROUND
Hypertension is a risk factor for the development and exacerbation of atrial fibrillation (AF). Angiotensin-converting enzyme inhibitors are a standard-of-care treatment option for patients with hypertension; however, there is conflicting evidence about their effects on AF recurrence. Therefore, our objective was to assess the efficacy of perindopril, compared with placebo, to reduce AF recurrence in patients with hypertension and AF.
METHODS
In a multicenter, double-blind, placebo-controlled trial, patients with hypertension and symptomatic AF were randomly assigned (1:1) to perindopril or placebo based on a stratification factor of antiarrhythmic drug use. Patients with terminated AF were followed up from 30 days after randomization to 7 to 13 months. The primary endpoint was AF recurrence. Secondary endpoints included AF hospitalization, cardioversion, and blood pressure control. Recurrent events, AF burden, and safety endpoints were also investigated.
RESULTS
A total of 315 patients were randomly assigned, and 301 patients were included in the modified intent-to-treat analysis (155 vs 146 patients in the perindopril and placebo groups, respectively). The mean follow-up was 336 ± 70 days, and 91.1% of patients were compliant to the treatment medication throughout the study. After adjustment for baseline antiarrhythmic drugs, there was no statistically significant difference in the hazards of AF recurrence (hazard ratio, 1.22; 95% confidence interval, 0.92-1.61), with similar blood pressure. The incidence of secondary endpoints and adverse events also did not differ between treatment arms.
CONCLUSIONS
Perindopril does not reduce recurrence or the number of AF episodes in patients with hypertension and AF.
PubMed: 34712936
DOI: 10.1016/j.cjco.2021.04.014 -
Cardiology and Therapy Jun 2020Overweight and obesity are increasing worldwide and are associated with an increased risk for cardiovascular disease (CVD). The aim of this study was to examine the...
INTRODUCTION
Overweight and obesity are increasing worldwide and are associated with an increased risk for cardiovascular disease (CVD). The aim of this study was to examine the burden of CVD risk factors among normal weight, overweight, and obese subjects with hypertension, and to evaluate the effectiveness of switching to a single-pill combination (SPC) of perindopril arginine/indapamide for blood pressure (BP) control in overweight and obese subjects treated in routine clinical practice.
METHODS
FORSAGE was a 3-month, multicenter, observational, open-label study conducted in Russian patients with uncontrolled arterial hypertension under previous antihypertensive therapy. Subjects were switched to the full-dose perindopril arginine 10 mg/indapamide 2.5 mg SPC. BP was assessed at 2 weeks, 1 month, and 3 months, and serum creatinine and general health status at 3 months. The present post hoc analysis of the FORSAGE study results explored the effectiveness of perindopril arginine/indapamide SPC in patients with arterial hypertension with regard to baseline body mass index (BMI): normal (< 25 kg/m), overweight (25 ≤ BMI < 30 kg/m), and obese (≥ 30 kg/m).
RESULTS
A total of 1969 patients were recruited, but BMI data were available for 1963 patients, two-thirds of whom were women. The distribution of BMI groups was as follows: < 25 kg/m (16.7%), overweight (48.7%), and obese (34.7%). Overweight or obese patients had more concomitant diseases such as diabetes mellitus or history of stroke, higher BP levels, serum cholesterol and creatinine, and lower glomerular filtration rates. Switching to perindopril arginine/indapamide SPC was associated with a statistically significant reduction in BP as early as the second week of treatment. At 3 months, systolic blood pressure (SBP)/diastolic blood pressure (DBP) had decreased significantly by 39.3/18.8 mmHg in the normal BMI group, 39.8/18.8 mmHg in overweight, and 39.4/18.7 mmHg in obese groups. The magnitude of the BP reduction was independent of BMI. Achievement of target BP (< 140/90 mmHg) was good in all groups, but lower in obese subjects (70.9%) than in overweight subjects (78.1%) or those with a normal BMI (81.8%) (P < 0.0001 for both comparisons).
CONCLUSIONS
In subjects with uncontrolled BP on existing antihypertensive therapy, switching to perindopril arginine 10 mg/indapamide 2.5 mg was associated with statistically significant decreases in BP and higher rates of target BP achievement in all BMI groups, including more than 70% of overweight and obese patients.
TRIAL REGISTRATION
ISRCTN ID, ISRCTN14315146 (retrospectively registered 18/11/2019).
PubMed: 32008207
DOI: 10.1007/s40119-020-00162-x -
British Journal of Pharmacology Dec 2018The endocannabinoid (EC) system has been implicated in the pathogenesis of diabetic nephropathy (DN). We investigated the effects of peripheral blockade of the...
BACKGROUND AND PURPOSE
The endocannabinoid (EC) system has been implicated in the pathogenesis of diabetic nephropathy (DN). We investigated the effects of peripheral blockade of the cannabinoid CB receptor as an add-on treatment to ACE-inhibition in type 1 diabetic mice (DM) with established albuminuria.
EXPERIMENTAL APPROACH
Renal functional parameters (albumin excretion rate, creatinine clearance), tubular injury, renal structure, both EC and CB receptor levels and markers of podocyte dysfunction, fibrosis and inflammation were studied in streptozotocin-induced DM treated for 14 weeks with vehicle, the ACE-inhibitor perindopril (2 mg·kg ·day ), peripherally-restricted CB receptor antagonist AM6545 (10 mg·kg ·day ) or both. Treatments began at 8 weeks after diabetes onset, when early DN is established.
KEY RESULTS
CB receptors were overexpressed in DM and neither perindopril nor AM6545 altered this effect, while both drugs abolished diabetes-induced overexpression of angiotensin AT receptors. Single treatment with either AM6545 or perindopril significantly reduced progression of albuminuria, down-regulation of nephrin and podocin, inflammation and expression of markers of fibrosis. However, reversal of albuminuria was only observed in mice administered both treatments. The ability of the combination therapy to completely abolish slit diaphragm protein loss, monocyte infiltration, overexpression of inflammatory markers and favour macrophage polarization towards an M2 phenotype may explain this greater efficacy. In vitro experiments confirmed that CB receptor activation directly inhibits retinoic acid-induced nephrin expression in podocytes and IL-4-induced M2 polarization in macrophages.
CONCLUSION AND IMPLICATIONS
Peripheral CB receptor blockade used as add-on treatment to ACE-inhibition reverses albuminuria, nephrin loss and inflammation in DM.
Topics: Albuminuria; Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Male; Mice; Mice, Inbred C57BL; Morpholines; Perindopril; Pyrazoles; Receptor, Cannabinoid, CB1
PubMed: 30184259
DOI: 10.1111/bph.14495 -
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 -
Heliyon Mar 2023The fixed-dose combination of Amlodipine Besylate (ADB) with Perindopril Tertbutylamine (PTBA) drug is used to treat patients with mild-to-moderate hypertension. In...
The fixed-dose combination of Amlodipine Besylate (ADB) with Perindopril Tertbutylamine (PTBA) drug is used to treat patients with mild-to-moderate hypertension. In recent times researchers are interested to find the efficient analytical method development and validation for the simultaneous determination of ADB and PTBA in a fixed-dose, film-coated tablet. Therefore, the current study was performed with a reverse-phase liquid chromatography method developed to simultaneously analyze ADB and PTBA in film-coated tablets as fixed-dose combinations. The linearity of the proposed method was calculated by preparing six different mixtures of both ADB and PTBA in the mobile phase. The concentration of both the analytes was analyzed at 56mg/100 mL to 84mg/100 mL and 32mg/100 mL to 48mg/100 mL, respectively. The ratio of acetonitrile and phosphate buffer was 35:65. The flow rate was adjusted to 1.5 ml per minute to reduce the retention time. The validation study was performed for the parameters specificity, linearity, precision, range, limit of detection, limit of quantification, accuracy/biasness, and robustness. The relative percentage standard deviation for Perindopril Tertbutyl amine was 0.148%, and for Amlodipine is 0.312%. These results show that the advanced analysis method for simultaneous analysis of fixed-dose is precise. The theoretical IR spectra were also calculated by Gaussian 9.2 by employing the B3LYP functional at density functional theory (DFT) level study. All these parameters studied in this work authenticate the effectiveness of the developed validation method and ensure its repeatability/reproducibility accordingly. To the best of our knowledge, this is the first time to develop a new fast, and easy method for simultaneous identification and quantification of ADB and PTBA by high-performance liquid chromatography (HPLC) with a time-efficient and cost-effective approach.
PubMed: 36923897
DOI: 10.1016/j.heliyon.2023.e14209 -
Ochsner Journal 2014Angiotensin-converting enzyme (ACE) inhibitors are highly effective at improving prognosis in a variety of disease states such as hypertension, cardiovascular disease,...
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors are highly effective at improving prognosis in a variety of disease states such as hypertension, cardiovascular disease, systolic heart failure, and acute coronary syndrome. Although these medications have been used in clinical practice for decades, not all ACE inhibitors are equal, as agents within this class vary in lipophilicity, tissue-ACE binding, antioxidant properties, antiinflammatory properties, bradykinin site selectivity, and duration of action. The objective of this systematic review and metaanalysis was to evaluate the effects of perindopril vs enalapril on left ventricular function in patients with systolic heart failure.
METHODS
We conducted a systematic review and metaanalysis of trials comparing perindopril and enalapril in systolic heart failure. Relevant studies were identified through searches of MEDLINE, EMBASE, Web of Science, and Google Scholar.
RESULTS
Three trials comparing enalapril with perindopril in 116 patients with systolic heart failure were identified. Compared to enalapril, perindopril significantly improved cardiac sympathetic nerve activity: the pooled mean net change in heart to mediastinum ratio was 0.12 (95% confidence interval [CI]: 0.08, 0.16) and the pooled mean net change in washout rate was -3.51% (95% CI: -4.17, -2.85). Other variables also showed improvement. The pooled mean net change in New York Heart Association functional class was -0.44 (95% CI: -0.86, -0.03) and the change in brain natriuretic peptide was -64.1 [95% CI: -80.8, -47.4]. The change in left ventricular ejection fraction was not significantly greater with perindopril than enalapril: 1.15% (95% CI: -2.74, 5.04). However, in the 2 trials that switched patients from enalapril to perindopril, left ventricular ejection fraction at 6 months was significantly greater in the perindopril group: 2.41% (95% CI: 1.26, 3.55; P<0.0001).
CONCLUSION
In patients with systolic heart failure, perindopril significantly improves cardiac sympathetic nerve activity, brain natriuretic peptide, and New York Heart Association functional class compared to enalapril. Additionally, when patients were switched from enalapril to perindopril, left ventricular ejection fraction at 6 months was significantly greater.
PubMed: 25249801
DOI: No ID Found -
Acta Pharmaceutica (Zagreb, Croatia) Dec 2020Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study's aim was to assess the potential modulatory effect of perindopril on...
Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study's aim was to assess the potential modulatory effect of perindopril on cisplatin-induced nephrotoxicity and to elucidate the possible underlying mechanisms. Renal dysfunction was induced in mice by a single injection of cisplatin (10 mg kg-1, i.p.) and perindopril was administered orally (2 mg kg-1, once daily) for 5 days. Perindopril remarkably ameliorated cisplatin-induced perturbations in renal histology, renal levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-10, apoptosis-regulating protein expressions (Bax and Bcl2), and partially normalized Bax to Bcl2 ratio and active caspase 3 protein expression. Conversely, perindopril had no significant effect on cisplatin-induced elevations in serum creatinine and urea, microalbuminuria, kidney to body weight ratio, lipid peroxidation marker, superoxide dismutase and catalase activities and reduced glutathione content. In conclusion, perindopril may be safely used with cisplatin in mice since it ameliorated cisplatin-induced histopathological changes, inflammation and apoptosis without affecting renal biomarkers or oxidative stress.
Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Caspase 3; Cisplatin; Cytokines; Inflammation; Kidney Diseases; Kidney Function Tests; Lipid Peroxidation; Male; Mice; Oxidative Stress; Perindopril
PubMed: 32412432
DOI: 10.2478/acph-2020-0033