-
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 -
European Heart Journal. Cardiovascular... Feb 2022An improved understanding of the pathophysiology of trastuzumab-mediated cardiotoxicity is required to improve outcomes of patients with human epidermal growth factor... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
An improved understanding of the pathophysiology of trastuzumab-mediated cardiotoxicity is required to improve outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to characterize the cardiac and cardiometabolic phenotype of trastuzumab-mediated toxicity and potential interactions with cardiac pharmacotherapy.
METHODS AND RESULTS
This study was an analysis of serial magnetic resonance imaging (MRI) and circulating biomarker data acquired from patients with HER2-positive early-stage breast cancer participating in a randomized-controlled clinical trial for the pharmaco-prevention of trastuzumab-associated cardiotoxicity. Circulating biomarkers (B-type natriuretic peptide, troponin I, MMP-2 and -9, GDF-15, neuregulin-1, and IGF-1) and MRI of cardiac structure and function and abdominal fat distribution were acquired prior to trastuzumab, post-cycle 4 and post-cycle 17. Ninety-four participants (51 ± 8 years) completed the study with 30 on placebo, 33 on perindopril, and 31 on bisoprolol. Post-cycle 4, global longitudinal strain deteriorated from baseline in both placebo (+2.0 ± 2.7%, P = 0.002) and perindopril (+0.9 ± 2.5%, P = 0.04), but not with bisoprolol (-0.2 ± 2.1%, P = 0.55). In all groups combined, extracellular volume fraction and GDF-15 increased post-cycle 4 (+1.3 ± 4.4%, P = 0.004; +130 ± 150%, P ≤ 0.001, respectively). However, no significant change in troponin I was detected throughout trastuzumab. In all groups combined, visceral and intermuscular fat volume increased post-cycle 4 (+7 ± 17%, P = 0.02, +8 ± 23%, P = 0.02, respectively), while muscle volume and IGF-1 decreased from post-cycle 4 to 17 (-2 ± 10%, P = 0.008, -18 ± 28%, P < 0.001, respectively).
CONCLUSION
Trastuzumab results in impaired cardiac function and early myocardial inflammation. Trastuzumab is also associated with deleterious changes to the cardiometabolic phenotype which may contribute to the increased cardiovascular risk in this population.
Topics: Breast Neoplasms; Cardiotoxicity; Female; Humans; Natriuretic Peptide, Brain; Trastuzumab; Troponin I
PubMed: 33605416
DOI: 10.1093/ehjcvp/pvab016 -
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 -
Cells Mar 2021(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible...
(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible influence on inflammatory and anti-inflammatory pathways. We aimed to study the effects of newly initiated antihypertensive drugs on angiotensin (Ang) II and Ang (1-7) as representers of two counter-regulatory axes. (2) Methods: In this randomized, open-label trial investigating RAAS peptides after the initiation of perindopril, olmesartan, amlodipine, or hydrochlorothiazide, Ang II and Ang (1-7) equilibrium concentrations were measured at 8 a.m. and 12 a.m. at baseline and after four weeks of treatment. Eighty patients were randomized (1:1:1:1 fashion). (3) Results: Between the four substances, we found significant differences regarding the concentrations of Ang II ( < 0.0005 for 8 a.m., 12 a.m.) and Ang (1-7) ( = 0.019 for 8 a.m., <0.0005 for 12 a.m.) four weeks after treatment start. Ang II was decreased by perindopril ( = 0.002), and increased by olmesartan ( < 0.0005), amlodipine ( = 0.012), and hydrochlorothiazide ( = 0.001). Ang (1-7) was increased by perindopril and olmesartan ( = 0.008/0.002), but not measurably altered by amlodipine and hydrochlorothiazide ( = 0.317/ 0.109). (4) Conclusion: The initiation of all first line antihypertensive treatments causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptides shift upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Male; Middle Aged; Renin-Angiotensin System
PubMed: 33802464
DOI: 10.3390/cells10030534 -
Biomedicine & Pharmacotherapy =... Feb 2024Telmisartan is an antagonist of the angiotensin II receptor used in the management of hypertension (alone or in combination with other antihypertensive agents. It... (Review)
Review
Telmisartan is an antagonist of the angiotensin II receptor used in the management of hypertension (alone or in combination with other antihypertensive agents. It belongs to the drug class of angiotensin II receptor blockers (ARBs). Among drugs of this class, telmisartan shows particular pharmacologic properties, including a longer half-life than any other angiotensin II receptor blockers that bring higher and persistent antihypertensive activity. In hypertensive patients, telmisartan has superior efficacy than other antihypertensive drugs (losartan, valsartan, ramipril, atenolol, and perindopril) in controlling blood pressure, especially towards the end of the dosing interval. Telmisartan has a partial PPARγ-agonistic effect whilst does not have the safety concerns of full agonists of PPARγ receptors (thiazolidinediones). Moreover, telmisartan has an agonist activity on PPARα and PPARδ receptors and modulates the adipokine levels. Thus, telmisartan could be considered as a suitable alternative option, with multi-benefit for all components of metabolic syndrome including hypertension, diabetes mellitus, obesity, and hyperlipidemia. This review will highlight the role of telmisartan in metabolic syndrome and the main mechanisms of action of telmisartan are discussed and summarized. Many studies have demonstrated the useful properties of telmisartan in the prevention and improving of metabolic syndrome and this well-tolerated drug can be greatly proposed in the treatment of different components of metabolic syndrome. However, larger and long-duration studies are needed to confirm these findings in long-term observational studies and prospective trials and to determine the optimum dose of telmisartan in metabolic syndrome.
Topics: Humans; Telmisartan; Angiotensin Receptor Antagonists; Metabolic Syndrome; PPAR gamma; Prospective Studies; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Hypertension; Antihypertensive Agents; Blood Pressure; Benzoates
PubMed: 38228033
DOI: 10.1016/j.biopha.2024.116169 -
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 -
Drug Design, Development and Therapy 2020This study aimed to quantify the amount of perindopril and its active metabolite perindoprilat present in breast milk and corresponding maternal and infant plasma... (Observational Study)
Observational Study
OBJECTIVE
This study aimed to quantify the amount of perindopril and its active metabolite perindoprilat present in breast milk and corresponding maternal and infant plasma concentrations.
DESIGN
Prospective, longitudinal, observational.
SETTING
Tertiary specialist paediatric and obstetric hospital in Adelaide, South Australia.
POPULATION
Breastfeeding women actively treated with perindopril for hypertensive disorders postpartum.
METHODS
Eight breast milk samples and a single plasma sample were collected from each participant over a 24 hrs period, and plasma samples were taken from eligible breastfed infants. Breast milk and plasma concentrations of perindopril and perindoprilat were analysed using a validated Liquid Chromatography tandem-Mass Spectrometry (LC-MS/MS) method.
MAIN OUTCOME MEASURES
Mean breast milk concentrations of perindopril and perindoprilat, Relative Infant Dose (RID) <10%, and Theoretical Infant Dose (TID).
RESULTS
Ten women and three infants participated in the study. The mean concentration of perindopril in breast milk for each participant ranged from 0.003 to 1.2 ng/mL and perindoprilat 0.2-36 ng/mL. RID for perindopril was 0.0005-0.2% and perindoprilat 0.03-4.6%. TID for perindopril was 0.00045-0.18 µg/kg/day and perindoprilat 0.032-5.4 µg/kg/day. Infant plasma levels for perindopril ranged from 0.44 to 1.12 ng/mL and perindoprilat undetectable - 10.14 ng/mL. Maternal reports described normal infant growth and development.
CONCLUSION
Infant exposure to perindopril and perindoprilat through breast milk is low. However, some infants were found to have plasma perindoprilat concentrations consistent with pharmacodynamic effects. Perindopril may be used in mothers of healthy term infants, provided the infant is carefully monitored.
Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Breast Feeding; Female; Humans; Indoles; Infant; Male; Middle Aged; Milk, Human; Perindopril; Prospective Studies; Young Adult
PubMed: 32184565
DOI: 10.2147/DDDT.S239704 -
Heliyon Feb 2022Alzheimer's disease (AD) is a common neurodegenerative disorder. Aluminium chloride induces AD like pathology in rats. Renin angiotensin system plays a significant role...
Alzheimer's disease (AD) is a common neurodegenerative disorder. Aluminium chloride induces AD like pathology in rats. Renin angiotensin system plays a significant role in the pathogenesis and occurrence of Alzheimer's disease. In the present study we evaluated and compared the effect of Captopril and Perindopril against aluminium chloride induced amyloidogenesis and cognitive dysfunction in rats. Wistar rats of both sex were divided randomly into four groups i.e. Group I was served as normal control and treated with normal saline, Group II was administered with AlCl (100 mg/kg, p. o.) and Group III and IV received Captopril (30 mg/kg, p. o.) and Perindopril (5 mg/kg, p. o.) respectively 1hr prior to administration of AlCl. All the doses were given once daily for 42 days. The evaluation of memory function was carried out in Y-maze (spontaneous alternation), radial arm maze (number of correct responses) and elevated plus maze (transfer latency). After behavioral studies, estimation of antioxidant status (brain and serum), amyloid-β content (brain) and histopathology of brain hippocampus region was done. Administration of AlCl for 42 days impaired cognitive dysfunction. Captopril and Perindopril prevented AlCl induced cognitive dysfunction by improving spontaneous alternation behavior, number of correct responses and reducing transfer latency. They also increase the antioxidant status, reduce the Aβ42 content in the brain and reverse the histopathological changes caused by AlCl in hippocampal region. Both Captopril and Perindopril protects against aluminium chloride induced amyloidogenesis and AD like pathology. Captopril is found to be more effective than Perindopril.
PubMed: 35243060
DOI: 10.1016/j.heliyon.2022.e08935 -
Revue Medicale de Liege Mar 2020Angiotensin converting enzyme inhibitors (ACE-i) are the most common cause of bradykininin angioedema. These bradykinin-mediated angioedemas are sometimes confused with...
Angiotensin converting enzyme inhibitors (ACE-i) are the most common cause of bradykininin angioedema. These bradykinin-mediated angioedemas are sometimes confused with histamine-induced angioedema, which may cause a late diagnosis and hence poor initial management, deleterious to the patient. This report describes a patient with a bradykinin-mediated angioedema soon after the initiation of perindopril, with laryngeal involvement requiring orotracheal intubation in emergency. The diagnosis was confirmed later and the assay of the activity of the enzymes involved in the catabolism of kinins - aminopeptidase P (APP), carboxypeptidase N (CPN) and Angiotensin-Converting Enzyme (ACE) - demonstrated a decrease of activity of both APP and ACE. As the diagnosis was not made initially, the specific treatments - concentrate of C1 inhibitor or antagonist of the B2 receptor of bradykinin (Icatibant) - were not administered. Any angioedema occurring during a treatment with ACE-i should be considered as a bradykinin-mediated angioedema.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Emergency Service, Hospital; Humans; Perindopril
PubMed: 32157838
DOI: No ID Found -
Acta Dermatovenerologica Croatica : ADC Aug 2023Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly...
Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly in flexural areas (1,2). This helps us to differentiate it from PV of Neumann, which is a more extensive and refractory disease, more alike to a pemphigus vulgaris outbreak with blisters which turn into vegetating plaques (3). We report the clinical presentation, course, and therapeutic response in a patient diagnosed with PV of Hallopeau from its early stage during a 3-year follow up. A 62-year-old man, non-smoker, presented at our clinic in July 2018 with hemorrhagic-serous crusts and fissures on the vermilion of the lower lip (Figure 1, a) and two merged circinate, sharply demarcated plaques on the right side of the groin (Figure 1, b). Plaque margins were elevated, with hypertrophic granulation tissue studded with pustules. Mucosal and cutaneous lesions persisted 6 and 4 weeks, respectively. The rest of the mucosa and skin were unaffected; the general state was good. The patient's family history for skin diseases was negative. The medical history included hypertension, atherosclerosis and hypercholesterolemia, hiatus hernia, and recent surgery (3 months prior) of an aortic abdominal aneurysm with reconstruction and synthetic graft placement. He was taking antihypertensives (fixed combination of 3 drugs, among them the ACE-inhibitor perindopril) with well-regulated blood pressure, statins, a pump-proton inhibitor, and acetylsalicylic acid. Differential blood count revealed eosinophilia. Histopathology finding showed acanthosis, suprabasal clefting with a suprabasilar bulla and acantholysis, prominent eosinophilic intraepidermal spongiosis, and heavy dermal infiltration of eosinophils and lymphocytes (Figure 2, a and b). The diagnosis of pemphigus was confirmed by direct immunofluorescence (DIF), which detected C3 deposits on the surface of keratinocytes throughout the epidermis of perilesional skin. Circulating pemphigus antibodies were detected by indirect IF. Only Dsg 3 antibodies were detected using an ELISA assay (233.23 RU/mL). After establishing the diagnosis of PV of Hallopeau, treatment with prednisolone 0.75 mg/kg/day orally in combination with adjuvant immunosuppression (azathioprine 100 mg daily) was started. Appropriate topical therapy with local steroids and antiseptic was applied. The steroid dose was titrated and gradually tapered down to the minimum required to control the disease - 10 mg. One-year remission was achieved. Azathioprine was withdrawn in October 2019 and since then the patient experienced a flare-up twice. The control of pemphigus flare-ups was achieved by a low dose of steroids (30 mg prednisolone orally). It remains debatable whether surgical trauma and radiology procedures such as angiographies (4) well as ACE-inhibitor drugs (5) triggered or aggravated the pemphigus. Early recognition and correct diagnosis of this rare type of pemphigus allows us to treat and control the disease successfully with lower doses of steroids, reducing complications to the minimum.
Topics: Male; Humans; Middle Aged; Pemphigus; Azathioprine; Skin; Eosinophilia; Blister; Prednisolone; Steroids
PubMed: 37843091
DOI: No ID Found