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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 -
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 -
The Cochrane Database of Systematic... Oct 2018The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years,...
BACKGROUND
The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further.
OBJECTIVES
To assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months.
SEARCH METHODS
On 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies.
SELECTION CRITERIA
We considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria.
MAIN RESULTS
We included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.The randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).A study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) -0.60% CI -6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).A study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD -0.20%, 95% CI -3.07 to 2.67, N = 21), and for ejection fraction the mean change was -1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD -2.30%, 95% CI -9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between the treatment and placebo groups (low-certainty evidence).A multicentre controlled study added eplerenone or placebo to 42 patients with DMD with early cardiomyopathy but preserved left ventricular function already established on ACEI or ARB therapy. Results showed that eplerenone slowed the rate of decline of magnetic resonance (MR)-assessed left ventricular circumferential strain at 12 months (eplerenone group median 1.0%, interquartile range (IQR) 0.3 to -2.2; placebo group median 2.2%, IQR 1.3 to -3.1%; P = 0.020). The median decline in LVEF over the same period was also less in the eplerenone group (-1.8%, IQR -2.9 to 6.0) than in the placebo group (-3.7%, IQR -10.8 to 1.0; P = 0.032). We downgraded the certainty of evidence to very low for study limitations and serious imprecision. Serious adverse events were reported in two patients given placebo but none in the treatment group (very low-certainty evidence).A randomised placebo-controlled study of subcutaneous growth hormone in 16 participants with DMD or BMD showed an increase in left ventricular mass after three months' treatment but no significant improvement in cardiac function. The evidence was of very low certainty due to imprecision, indirectness, and study limitations. There were no clinically significant adverse events (very low-certainty evidence).Some studies were at risk of bias, and all were small. Therefore, although there is some evidence from non-randomised data to support the prophylactic use of perindopril for cardioprotection ahead of detectable cardiomyopathy, and for lisinopril or losartan plus eplerenone once cardiomyopathy is detectable, this must be considered of very low certainty. Findings from non-randomised studies, some of which have been long term, have led to the use of these drugs in daily clinical practice.
AUTHORS' CONCLUSIONS
Based on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.
Topics: Adolescent; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiovascular Agents; Child; Disease Progression; Eplerenone; Human Growth Hormone; Humans; Lisinopril; Losartan; Male; Muscular Dystrophy, Duchenne; Non-Randomized Controlled Trials as Topic; Perindopril; Placebos; Randomized Controlled Trials as Topic; Stroke Volume; Ubiquinone; Young Adult
PubMed: 30326162
DOI: 10.1002/14651858.CD009068.pub3 -
Biomedical Papers of the Medical... Jun 2018Patients who are unable to receive oral medication (p.o.) are a major problem in outpatient settings, especially in home health care systems. Mucosal administration of... (Review)
Review
Patients who are unable to receive oral medication (p.o.) are a major problem in outpatient settings, especially in home health care systems. Mucosal administration of drugs offers an alternative to the oral route, especially when the parenteral mode cannot be used. There are three main pathways of mucosal administration: sublingual/buccal, intranasal and rectal. We discuss the possibility of mucosal delivery of antihypertensive drugs. Perindopril arginine and Amlodipine besylate are registered in the EU as orodispersible tablets for oromucosal delivery, however, they are not available in all countries. For this reason, we describe other drugs suitable for mucosal delivery: Captopril and Nitrendipine in the sublingual system and Metoprolol tartrate, Propranolol and Furosemide by the transrectal route. Based on the published data and common clinical practice we discuss the use of mucosal delivery systems of all these antihypertensive drugs with special attention to their pharmacokinetics. We illustrate this mini-review with a case report of the prolonged-term use of mucosal delivery of sublingual Captopril and Nitrendipine combined with rectal Metoprolol tartrate and Furosemide in a patient with severe hypertension unable to receive medication p.o. This is also a report on the first human use of Furosemide-containing suppositories as well as prolonged-term transmucosal administration of these four drugs, describing a practical approach leading to successful control of severe hypertension with four antihypertensive drugs delivered via the mucosal route. The treatment was effective and without side effects; however, the long-term safety and efficacy of such therapy must be confirmed by randomized clinical trials.
Topics: Administration, Sublingual; Antihypertensive Agents; Female; General Practice; Humans; Hypertension; Middle Aged; Treatment Outcome
PubMed: 29765168
DOI: 10.5507/bp.2018.022 -
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 -
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 -
Cardiology and Therapy Dec 2019The functional integrity of the endothelium is essential for vascular health. In addition to maintaining a delicate balance between vasodilation and vasoconstriction,... (Review)
Review
The functional integrity of the endothelium is essential for vascular health. In addition to maintaining a delicate balance between vasodilation and vasoconstriction, the endothelium has numerous other complex roles involved in the maintenance of vascular homeostasis. Chronic exposure to cardiovascular risk factors and oxidative stress results in an imbalance in these functions, creating an environment that favors reduced vasodilation and a proinflammatory and prothrombic state. The involvement of endothelial dysfunction in all stages of the cardiovascular continuum makes it an important target for treatment. One of the major endothelial-derived factors involved in the maintenance of endothelial function is nitric oxide (NO). Angiotensin-converting enzyme (ACE) inhibitors increase NO production both directly and indirectly by preventing production of angiotensin II (which diminishes NO production) and inhibiting the degradation of bradykinin (which stimulates local release of NO). Among the ACE inhibitors, perindopril appears to have the greatest effects on bradykinin and has demonstrated efficacy in a number of markers of endothelial dysfunction including arterial stiffness and progression of atherosclerosis. There is also strong evidence supporting the use of perindopril-based therapy for the treatment of hypertension and for reducing the risk of cardiovascular morbidity and mortality in a wide range of patients across the cardiovascular continuum.Funding: The journal's Rapid Service Fee was funded by Servier.
PubMed: 31578675
DOI: 10.1007/s40119-019-00150-w -
Journal of Diabetes Dec 2020Creatinine-based estimated glomerular filtration rate (eGFR) is biased in the setting of obesity and other conditions. Alternative kidney filtration markers may be... (Randomized Controlled Trial)
Randomized Controlled Trial
Alternative kidney filtration markers and the risk of major macrovascular and microvascular events, and all-cause mortality in individuals with type 2 diabetes in the ADVANCE trial.
BACKGROUND
Creatinine-based estimated glomerular filtration rate (eGFR) is biased in the setting of obesity and other conditions. Alternative kidney filtration markers may be useful in adults with diabetes, but few studies examined the associations with risk of clinical outcomes.
METHODS
In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, we evaluated whether baseline levels and change in eGFR based on creatinine (Cr), cystatin c (Cys), β -microglobulin (B2M), eGFR , and the average of three estimates (eGFR ) assessed in 7217 participants at baseline and a random sample of 640 participants at the 1-year visit are associated with clinical outcomes. We examined associations with major macrovascular and microvascular events together and separately and all-cause mortality using Cox regression models, adjusting for established risk factors.
RESULTS
Over a median follow-up of 5 years, 1313 major macrovascular (n = 748) and microvascular events (n = 637), and 743 deaths occurred. Lower levels of eGFR based on all filtration markers individually and combined were associated with 1.4 to 3.0 times higher risk of major macrovascular and microvascular events (combined and separately) and all-cause mortality. Per 30% decline in eGFR , eGFR , and eGFR were associated with a >2-fold higher risk of all clinical outcomes.
CONCLUSIONS
In adults with type 2 diabetes, baseline levels of eGFR based on alternative filtration markers and per 30% decline in eGFR , eGFR , and eGFR were associated with clinical outcomes. Measurement of alternative filtration markers, particularly B2M in adults with type 2 diabetes may be warranted.
Topics: Aged; Antihypertensive Agents; Biomarkers; Cause of Death; Creatinine; Cystatin C; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Indapamide; Male; Middle Aged; Outcome Assessment, Health Care; Perindopril; Risk Factors; Vascular Diseases; beta 2-Microglobulin
PubMed: 32609422
DOI: 10.1111/1753-0407.13083 -
Indian Heart Journal 2020Cough is one of the common adverse effects in patients receiving angiotensin-converting enzyme inhibitors (ACEIs). This review presents the current evidence on incidence... (Review)
Review
Cough is one of the common adverse effects in patients receiving angiotensin-converting enzyme inhibitors (ACEIs). This review presents the current evidence on incidence and mechanisms of cough associated with ACEIs use, and proposes a practical approach for managing the same for optimal cardiovascular (CV) risk reduction. The incidence of dry cough in patients receiving ACEIs vary among individual ACEIs, and is the lowest with perindopril. Cough is thought to originate from multiple mechanisms, bradykinin theory is the most commonly appealed hypothesis. The strategies for optimal management could be temporarily discontinuation of ACEI upon a reported incidence of cough and reintroduction after its remission. However, studies have reported disappearance of cough despite continuing treatment. Another important approach could be adding calcium channel blockers to ACEIs. Switching to alternative drugs such as angiotensin receptor blockers should be suggested in case intolerable symptoms recur and after exclusion of all other possible causes of cough.
Topics: Angiotensin Receptor Antagonists; Cardiovascular Diseases; Global Health; Humans; Incidence; Risk Factors; Risk Reduction Behavior
PubMed: 33189192
DOI: 10.1016/j.ihj.2020.08.007 -
Scientific Reports Jan 2024Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether...
Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether pharmacological inhibition of the angiotensin system would prevent diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes mellitus (T2DM). In the preclinical study, the nociceptive sensitivity was determined in leptin-deficient ob/ob mice, a T2DM model. A clinical retrospective cohort study was conducted, using the medical records of T2DM patients receiving antihypertensives at three hospitals for nearly a decade. In the ob/ob mice, daily treatment with perindopril, an angiotensin-converting enzyme inhibitor (ACEI), or telmisartan, an angiotensin receptor blocker (ARB), but not amlodipine, an L-type calcium channel blocker (CaB), significantly inhibited DPN development without affecting the hyperglycemia. In the clinical study, the enrolled 7464 patients were divided into three groups receiving ACEIs, ARBs and the others (non-ACEI, non-ARB antihypertensives). Bonferroni's test indicated significantly later DPN development in the ARB and ACEI groups than the others group. The multivariate Cox proportional analysis detected significant negative association of the prescription of ACEIs or ARBs and β-blockers, but not CaBs or diuretics, with DPN development. Thus, our study suggests that pharmacological inhibition of the angiotensin system is beneficial to prevent DPN accompanying T2DM.
Topics: Animals; Mice; Humans; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Antihypertensive Agents; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Retrospective Studies; Antiviral Agents
PubMed: 38200077
DOI: 10.1038/s41598-024-51572-z