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Current Oncology (Toronto, Ont.) Apr 2022Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the...
BACKGROUND
Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is limited by adverse cardiotoxic side effects. Both the nutraceutical agent flaxseed (FLX) and the pharmaceutical drug perindopril (PER) have been studied individually in the prevention of chemotherapy-mediated cardiac dysfunction. The objective of this study was to determine whether the prophylactic administration of FLX is comparable and/or synergistic with PER in preventing DOX + TRZ-induced cardiotoxicity.
METHODS
Over a six-week period, 81 wild-type C57Bl/6 female mice (8-12 weeks old) were randomized to receive regular chow (RC) or 10% FLX-supplemented diets with or without PER (3 mg/kg/week; oral gavage). Starting at week 4, mice were randomized to receive a weekly injection of saline or DOX (8 mg/kg) + TRZ (3 mg/kg). Serial echocardiography was conducted weekly and histological and biochemical analyses were performed at the end of the study.
RESULTS
In mice treated with RC + DOX + TRZ, left ventricular ejection (LVEF) decreased from 75 ± 2% at baseline to 37 ± 3% at week 6. However, prophylactic treatment with either FLX, PER, or FLX + PER partially preserved left ventricular systolic function with LVEF values of 61 ± 2%, 62 ± 2%, and 64 ± 2%, respectively. The administration of FLX, PER, or FLX + PER was also partially cardioprotective in preserving cardiomyocyte integrity and attenuating the expression of the inflammatory biomarker NF-κB due to DOX + TRZ administration.
CONCLUSION
FLX was equivalent to PER at preventing DOX + TRZ-induced cardiotoxicity in a chronic in vivo murine model.
Topics: Animals; Breast Neoplasms; Cardiotoxicity; Doxorubicin; Female; Flax; Humans; Mice; Mice, Inbred C57BL; Perindopril; Trastuzumab
PubMed: 35621631
DOI: 10.3390/curroncol29050241 -
Journal of Physiology and Pharmacology... Jun 2023Thrombotic events are highly prevalent in coronavirus disease 2019 (COVID-19), especially in patients presenting with risk factors of adverse outcomes such as obesity....
Thrombotic events are highly prevalent in coronavirus disease 2019 (COVID-19), especially in patients presenting with risk factors of adverse outcomes such as obesity. Recently, the associations between the angiotensin converting enzyme 2 (ACE2) pathway and thrombosis have been reported. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are widely used cardiovascular pharmacologic agents that upregulate ACE2 levels. An observation of the alterations in pro-coagulation factors after exposure to ACEIs and ARBs may provide valuable insight into the thrombosis mechanism and how it may relate to ACE2. This study use adipose tissue harvested from an obese male donor was isolated and exposed to perindopril, losartan, and ACE2 recombinant as binding assay, following exposure with 10 nm of SARS-CoV-2 S1 spike protein. After 48 hours, tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) as pro-coagulation factors as well as ACE2 levels and binding evaluated. The results shows TF level was significantly reduced in Perindopril group compared to control (4.834; p=0.005), while a non-significant reduction was observed in Losartan group (5.624; p=0.111). However, Losartan group showed a better reduction of PAI-1 levels (2.633; p≤0.001) than Perindopril group (3.484; p=0.001). These findings were consistent with the observations in ACE2 recombinant group, suggesting that both drugs lowered the bindings of ACE2 and SARS-CoV-2 spike proteins. This study indicated that both perindopril and losartan may attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike proteins, and therefore showcased a potential role of ACE2 in the mechanism of COVID-19-related thrombosis. Further investigation in non-COVID-19 populations should commence and may be of value to expanding this potential in general cardiovascular diseases.
Topics: Humans; Male; Perindopril; Spike Glycoprotein, Coronavirus; Losartan; Plasminogen Activator Inhibitor 1; Angiotensin-Converting Enzyme 2; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; COVID-19; SARS-CoV-2; Blood Coagulation Factors; Adipocytes; Thromboplastin; Cardiovascular Agents; Obesity
PubMed: 37661180
DOI: 10.26402/jpp.2023.3.03 -
Journal of Hypertension Mar 2023The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic indapamide monotherapy or in combination with perindopril as a blood pressure lowering drug in randomized controlled trials (RCTs).
METHOD
Aggregate data from four published RCTs conducted versus matching placebo were pooled: PATS, a 2-year study (indapamide), and PROGRESS, a 4-year study (indapamide and perindopril), both in patients with a history of stroke or transient ischemic attack; ADVANCE, a 4-year study in patients with type 2 diabetes and cardiovascular risk factor (single-pill combination perindopril/indapamide) and HYVET, a 2-year study in very elderly hypertensive individuals (indapamide and an option of perindopril). The pooled effect (fixed and random) estimate (hazard ratio) was reported with corresponding 95% confidence intervals and P values. Treatment discontinuations were also analysed to assess the net benefit of the treatment.
RESULTS
The population involved 24 194 patients (active: 12 113, placebo: 12 081). The fixed-effects meta-analysis of the three mortality endpoints found low statistical heterogeneity ( I2 = 0). Statistically significant risk reductions in the indapamide with or without perindopril-treated patients as compared to placebo were observed for all-cause death (-15%), cardiovascular death (-21%), fatal stroke (-36%) and all strokes (-27%). Other cardiovascular outcomes were improved (risk reduction, 22 to 36%). As expected, discontinuation rates for safety (two studies) were higher in the active group (6.4 vs. 3.9%), while they were similar when discontinuation for any reason is concerned (18.4 vs. 18.0%).
CONCLUSION
Across medium to high cardiovascular risk population, long-term indapamide, mostly combined with perindopril-based treatment, provided evidence of benefit on mortality and morbidity.
Topics: Humans; Aged; Perindopril; Indapamide; Antihypertensive Agents; Hypertension; Stroke; Drug Combinations; Blood Pressure; Randomized Controlled Trials as Topic
PubMed: 36633311
DOI: 10.1097/HJH.0000000000003368 -
Journal of Clinical Hypertension... Sep 2011The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized placebo-controlled trial which clearly demonstrated that perindopril-based blood... (Review)
Review
The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized placebo-controlled trial which clearly demonstrated that perindopril-based blood pressure (BP)-lowering treatment is one of the most effective and generalizable strategies for secondary prevention of stroke. Beneficial effects of BP lowering were observed on recurrent stroke, other cardiovascular events, disability, dependency, and cognitive function across a variety of subgroups defined by age, sex, geographical region, body mass index, diabetes, atrial fibrillation, chronic kidney disease, and baseline BP levels. Once patients with stroke have stabilized, all patients should receive BP-lowering therapy irrespective of their BP levels. On the basis of recommendations from current international guidelines, BP should be lowered to <140/90 mm Hg in all patients with cerebrovascular disease and to <130/80 mm Hg if therapy is well tolerated.
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Perindopril; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; Treatment Outcome
PubMed: 21896153
DOI: 10.1111/j.1751-7176.2011.00530.x -
Journal of Cardiovascular Pharmacology... 2023Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly...
Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin-angiotensin-aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [ ≤ .05]). LVEDV was reduced by 8.4 mL and 3.2 mL, and LVESV by 17.9 mL and 10.8 mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant ( = .007). Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.
Topics: Humans; Adult; Middle Aged; Heart Failure; Stroke Volume; Cohort Studies; Perindopril; Ventricular Function, Left; Tetrazoles; Treatment Outcome; Valsartan; Angiotensin Receptor Antagonists; Drug Combinations
PubMed: 37635324
DOI: 10.1177/10742484231195019 -
Frontiers in Pharmacology 2023Uncontrolled blood pressure is a major risk factor for cardiovascular diseases. Fixed-dose combination (FDC) therapy offers a promising approach to addressing this... (Review)
Review
Uncontrolled blood pressure is a major risk factor for cardiovascular diseases. Fixed-dose combination (FDC) therapy offers a promising approach to addressing this challenge by providing a convenient single-tablet solution that enhances the effectiveness of blood pressure control. In our systematic review, we assess the effectiveness of perindopril/amlodipine FDC in managing blood pressure. We conducted a comprehensive search across four primary electronic databases, namely, PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of 8 February 2022. Additionally, we performed a manual search to find relevant articles. The quality of the selected articles was evaluated using the Study Quality Assessment Tools (SQAT) checklist from the National Institute of Health and the ROB2 tool from Cochrane. Our systematic review included 17 eligible articles. The findings show that the use of perindopril/amlodipine FDC significantly lowers blood pressure and enhances the quality of blood pressure control. Compared to the comparison group, the perindopril/amlodipine combination tablet resulted in a higher rate of blood pressure response and normalization. Importantly, perindopril/amlodipine FDC contributes to improved patient adherence with minimal side effects. However, studies conducted to date have not provided assessments of the cost-effectiveness of perindopril/amlodipine FDC. In summary, our analysis confirms the effectiveness of perindopril/amlodipine FDC in lowering blood pressure, with combination therapy outperforming monotherapy and placebo. Although mild adverse reactions were observed in a small subset of participants, cost-effectiveness assessments for this treatment remain lacking in the literature.
PubMed: 38410524
DOI: 10.3389/fphar.2023.1156655 -
Advances in Therapy Jun 2023This study assessed the real-life effectiveness of a single-pill combination (SPC) of bisoprolol/perindopril for controlling blood pressure (BP) and symptoms of angina... (Observational Study)
Observational Study
Effectiveness and Tolerability of Bisoprolol/Perindopril Single-Pill Combination in Patients with Arterial Hypertension and a History of Myocardial Infarction: The PRIDE Observational Study.
INTRODUCTION
This study assessed the real-life effectiveness of a single-pill combination (SPC) of bisoprolol/perindopril for controlling blood pressure (BP) and symptoms of angina in patients with hypertension and a history of myocardial infarction (MI).
METHODS
Eligible patients with arterial hypertension and a history of MI were aged 18-79 years and had initiated bisoprolol/perindopril SPC within 3 months of study enrollment as part of routine Russian clinical practice. The primary endpoint was mean change in systolic and diastolic BP (SBP/DBP) at week 12 compared with baseline (data collected retrospectively). Secondary endpoints were assessed at weeks 4 and 12 and included mean change in resting heart rate (HR), proportion of patients reaching target level of resting HR, antianginal effectiveness of the SPC, and proportion of patients reaching target BP levels.
RESULTS
A total of 504 patients were enrolled, of whom 481 comprised the full analysis set (mean age 61.4 ± 8.9 years, 68% men). Mean baseline SBP/DBP and HR values were 148.9 ± 16.8/87.7 ± 11.0 mmHg and 77.4 ± 10.5 bpm, respectively. Mean durations of hypertension and CAD were 12.8 ± 8.4 and 6.1 ± 6.3 years, respectively, and time since MI was 3.8 ± 5.3 years. At week 12, SBP/DBP had decreased by 24.9/12.2 mmHg (P < 0.001 vs baseline). Target BP (< 140/90 mmHg) was achieved by 69.8% and 95.9% of patients at weeks 4 and 12, respectively, and target HR (55-60 bpm) by 17.3% and 34.5% at weeks 4 and 12 versus 3.1% at baseline (P < 0.001). Reductions in angina attacks, nitrate consumption, and improvements in HR were statistically significant. Treatment was well tolerated.
CONCLUSION
Treatment of symptomatic patients with CAD, hypertension, and a history of MI with a bisoprolol/perindopril SPC was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by improvements in angina symptoms and reductions in HR in a broad patient population representative of those seen in everyday clinical practice.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier NCT04656847.
Topics: Male; Humans; Middle Aged; Aged; Female; Perindopril; Bisoprolol; Antihypertensive Agents; Retrospective Studies; Hypertension; Blood Pressure; Myocardial Infarction; Angina Pectoris; Drug Combinations; Treatment Outcome
PubMed: 37029871
DOI: 10.1007/s12325-023-02462-9 -
American Family Physician Aug 2002When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors were indicated only for treatment of refractory hypertension. Since then, they have been... (Review)
Review
When first introduced in 1981, angiotensin-converting enzyme (ACE) inhibitors were indicated only for treatment of refractory hypertension. Since then, they have been shown to reduce morbidity or mortality in congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Pathologies underlying these conditions are, in part, attributable to the renin-angiotensin-aldosterone system. Angiotensin II contributes to endothelial dysfunction. altered renal hemodynamics, and vascular and cardiac hypertrophy. ACE inhibitors attenuate these effects. Clinical outcomes of ACE inhibition include decreases in myocardial infarction (fatal and nonfatal), reinfarction, angina, stroke, end-stage renal disease, and morbidity and mortality associated with heart failure. ACE inhibitors are generally well tolerated and have few contraindications. (Am Fam Physician 2002;66:473.)
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Captopril; Cardiovascular Diseases; Clinical Trials as Topic; Contraindications; Diabetic Nephropathies; Drug Costs; Enalapril; Fosinopril; Heart Failure; Humans; Hypertension; Indoles; Isoquinolines; Lisinopril; Meta-Analysis as Topic; Myocardial Infarction; Perindopril; Quinapril; Ramipril; Renin-Angiotensin System; Risk; Tetrahydroisoquinolines; United States
PubMed: 12182524
DOI: No ID Found -
British Journal of Pharmacology Mar 2021Fibrosis is a hallmark of chronic kidney disease (CKD) that significantly contributes to renal dysfunction, and impairs the efficacy of stem cell-based therapies. This...
BACKGROUND AND PURPOSE
Fibrosis is a hallmark of chronic kidney disease (CKD) that significantly contributes to renal dysfunction, and impairs the efficacy of stem cell-based therapies. This study determined whether combining bone marrow-derived mesenchymal stem cells (BM-MSCs) with the renoprotective effects of recombinant human relaxin (serelaxin) could therapeutically reduce renal fibrosis in mice with one kidney/deoxycorticosterone acetate/salt (1K/DOCA/salt)-induced hypertension, compared with the effects of the ACE inhibitor, perindopril.
EXPERIMENTAL APPROACH
Adult male C57BL/6 mice were uni-nephrectomised and received deoxycorticosterone acetate and saline to drink (1K/DOCA/salt) for 21 days. Control mice were uni-nephrectomised but received water over the same time period. Sub-groups of 1K/DOCA/salt-injured mice (n = 5-8 per group) were treated with either serelaxin (0.5 mg·kg ·day ) or BM-MSCs (1 × 10 per mouse) alone; both treatments combined (with 0.5 × 10 or 1 × 10 BM-MSCs per mouse); or perindopril (2 mg·kg ·day ) from days 14-21.
KEY RESULTS
1K/DOCA/salt-injured mice developed elevated BP and hypertension-induced renal damage, inflammation and fibrosis. BM-MSCs alone reduced the injury-induced fibrosis and attenuated BP to a similar extent as perindopril. Serelaxin alone modestly reduced renal fibrosis and effectively reduced tubular injury. Strikingly, the combined effects of BM-MSCs (at both doses) with serelaxin significantly inhibited renal fibrosis and proximal tubular epithelial injury while restoring renal architecture, to a greater extent than either therapy alone, and over the effects of perindopril.
CONCLUSION AND IMPLICATIONS
Combining BM-MSCs and serelaxin provided broader renoprotection over either therapy alone or perindopril and might represent a novel treatment for hypertensive CKD.
Topics: Animals; Blood Pressure; Desoxycorticosterone; Desoxycorticosterone Acetate; Hypertension; Hypertension, Renal; Kidney; Male; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL
PubMed: 33450051
DOI: 10.1111/bph.15361