-
Frontiers in Pharmacology 2022Adverse drug reaction (ADR) is one of the leading public health concerns associated with high mortality rate. Healthcare professionals, particularly pharmacists, have a...
Adverse drug reaction (ADR) is one of the leading public health concerns associated with high mortality rate. Healthcare professionals, particularly pharmacists, have a significant role in monitoring and preventing ADRs. This study was conducted on Malaysian Pharmaceutical Society (MPS) pharmacists who worked at the hospitals, health clinics, and community pharmacies to determine if pharmacists' experiences on ADRs are still the same 10 years later. In 2010, a postal survey and in 2020, an online survey were conducted among these pharmacists. A total of 472 pharmacists and 208 participated in 2010 and 2020, respectively. About 82% and 90% of hospital/health clinic pharmacists (HCPs) observed an ADR over the last 6 months in 2010 and 2020, while 60% and 100% community pharmacists in 2010 and 2020 observed an ADR, respectively. Perindopril was the top drug (HCPs: = 0.657; CPs: = 0.98), and rash was the top ADR reported by the pharmacists in both years (HCPs: < 0.001; CPs: = 0.679). The most common actions taken by HCPs in 2010 were to report the ADR ( = 0.343), while in 2020, most HCPs explained to patients regarding the reaction ( = 0.061), which was also the same in the CP group in 2020 ( = 0.958). The top factor encouraging ADR reporting in both years and both pharmacist groups was the high degree of severity of the reaction (HCPs: < 0.001; CPs: = 0.769). While the top factors discouraging ADR reporting were a lack of information from the affected patients (HCPs: = 0.2; CPs: = 0.656), reaction is widely known (HCPs: = 0.001; CPs: = 0.144) and uncertainty of the causal relationship (HCPs: = 0.169; CPs: = 0.609). Majority of the pharmacists agreed that severe reactions should be reported (HCPs: = 0.158; CPs: = 0.501) and the main aim for reporting is to measure the incidence of ADRs (HCPs: = 0.148; CPs: = 0.762). Despite being able to identify ADRs during the daily practice, many pharmacists especially community pharmacists are not reporting them. There is a misconception on the purpose of reporting ADRs. An interventional program and ADR reporting training would be a useful step in improving ADR reporting practice.
PubMed: 36249772
DOI: 10.3389/fphar.2022.932942 -
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 -
Journal of Pharmaceutical Analysis Oct 2018Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by...
Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by hyphenated ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Indapamide-d3, perindopril-d4 and perindoprilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C column (4.6 mm × 100 mm, 2.4 µm) for indapamide and perindopril simultaneously following a protein precipitation pretreatment of the biosamples. The separation of perindoprilat was achieved independently on a phenomenex PFP column (4.6 mm × 150 mm, 5 µm). All the analytes were quantitated with positive electrospray ionization and multiple reactions monitoring mode. The assay exhibited a linear range of 1-250 ng/mL for indapamide, 0.4-100 ng/mL for perindopril and 0.2-20 ng/mL for perindoprilat. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to the pharmacokinetic study of perindopril tert-butylamine/indapamide compound tablets in Chinese healthy volunteers and the comparative pharmacokinetic study between plasma and whole blood.
PubMed: 30345148
DOI: 10.1016/j.jpha.2018.05.004 -
Frontiers in Cardiovascular Medicine 2022β-blockers have been recommended for patients with heart failure (HF) and atrial fibrillation (AF), but studies have shown that β-blockers do not reduce all-cause...
BACKGROUND
β-blockers have been recommended for patients with heart failure (HF) and atrial fibrillation (AF), but studies have shown that β-blockers do not reduce all-cause mortality or cardiovascular mortality in patients with HF and AF.
OBJECTIVE
To investigate the difference in efficacy between oral amiodarone and metoprolol succinate for patients with HF with reduced ejection fraction (HFrEF) and persistent atrial fibrillation (pAF) with rapid ventricular response (RVR).
METHODS
Patients with HFrEF complicated with pAF with RVR treated in the People's Hospital of Chongqing Hechuan between March 2018 and March 2019 were enrolled in this prospective observational study. The primary outcomes were cardiovascular mortality and the first hospitalization for HF rate. The secondary outcomes were type B pro-brain natriuretic peptide (NT-proBNP) before/after treatment, left ventricular ejection fraction (LVEF) before/after treatment, average heart rate (AhR), and the rate of sinus rhythm after 1 year of follow-up.
RESULTS
A total of 242 patients with HFrEF complicated with pAF with RVR were enrolled and divided into amiodarone + perindopril + spironolactone+ routine drug (amiodarone group, = 121) and metoprolol succinate + perindopril + spironolactone +routine drug (metoprolol succinate group, = 121) according to their treatment strategy. Cardiovascular mortality (4.9 vs. 12.4%, HR: 2.500, 95%CI: 1.002-6.237, = 0.040) and first hospitalization for HF (52.9 vs. 67.8%, HR: 1.281, 95%CI: 1.033-1.589, = 0.024) were significantly lower in the amiodarone group than in the metoprolol group. The mean ventricular rate in the amiodarone group was significantly lower than in the metoprolol group (64.5 ± 3.2 vs. 72.4 ± 4.2, < 0.001). After 1 year of follow-up, the sinus rhythm rate was significantly higher in the amiodarone group than in the metoprolol group (38.8 vs. 7.4%, HR: 0.191, 95%CI: 0.098-0.374, < 0.001). The difference in proBNP (3,914.88 vs. 2,558.07, < 0.001) and LVEF (-6.89 vs. -0.98, < 0.001) before and after treatment was significantly higher in the amiodarone group than in the metoprolol group.
CONCLUSION
In conclusion, in this prospective observational study, the amiodarone group had lower risk of cardiovascular death and the first hospitalization for HF than metoprolol in HFrEF and persistent atrial fibrillation (pAF) with RVR. The mechanism may be related to improved cardiac function, rhythm control and ventricular rate control.
REGISTRATION NUMBER
ChiCTR2200057816; Registered 7 March 2022-Retrospectively registered: http://www.medresman.org.cn/pub/cn/proj/projectshshow.aspx?proj=4222.
PubMed: 36698920
DOI: 10.3389/fcvm.2022.1029012 -
Neurology. Clinical Practice Oct 2021To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy...
OBJECTIVE
To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy (DMD) compared with placebo.
METHODS
This multicenter, parallel group, 1:1 patient randomized, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of left ventricular (LV) function, electrocardiogram, and adverse event reporting were performed 6 monthly. The primary outcome was change in ejection fraction between arms after 36 months. The study was approved by the National Research Ethics Service Committee East Midlands-Derby.
RESULTS
Eighty-five boys were recruited (76% on steroid therapy) and randomized to combination heart drugs or matched placebo. Group change in left ventricular ejection fraction (LVEF%) at 36 months from baseline was -2.2% ± 6.0% and -2.9% ± 6.1% in active and placebo arms (adjusted mean difference: -2.1, 95% CI -5.2 to 1.1). There was no difference between treatment arms over repeated assessments (analysis of variance) up to 36 months (trial arms = 0.53); arm-over-time ( = 0.44). Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function. Secondary outcomes did not differ between arms either. Thirty-six serious adverse events occurred none due to cardiac events or trial medication.
CONCLUSIONS
Combination therapy was well tolerated. Consistent with the previous prophylactic perindopril heart study, there was no evidence of group benefit after 36-month treatment.
CLASSIFICATION OF EVIDENCE
This study provides Class I evidence that combination perindopril-bisoprolol therapy was well tolerated but did not change decline in LVEF significantly in boys with DMD.
PubMed: 34840880
DOI: 10.1212/CPJ.0000000000001023 -
Cardiology and Therapy Jun 2020A symposium held at the 29th European Meeting on Hypertension and Cardiovascular Protection in Milan, Italy, discussed the potential impact and long-term benefits of... (Review)
Review
A symposium held at the 29th European Meeting on Hypertension and Cardiovascular Protection in Milan, Italy, discussed the potential impact and long-term benefits of early active management of cardiovascular disease (CVD) risk in patients with hypertension, and potential barriers to this strategy. Hypertension often aggregates with other cardiovascular risk factors, exponentially increasing morbidity and mortality. While effective therapies to treat hypertension exist, a substantial number of patients still experience major cardiovascular events. Two major issues account for these disappointing results: interventions initiated too late in the disease trajectory and lack of effective translation of the research findings into daily clinical practice. Results from genetic studies suggest that lifetime exposure to lower blood pressure (BP) and cholesterol levels due to protective gene mutations, can provide greater cardiovascular benefits than middle-/late-age interventions. Clinical guidelines suggest adding statins to BP-lowering therapies for further cardiovascular benefits in most hypertensive patients; however, real-world data show that physicians' compliance with these recommendations and patients' adherence to BP- and lipid-lowering treatments remain poor, resulting in poor risk factor control and an increased risk of adverse outcomes. The use of single-pill combinations (SPC) can partially mitigate these issues, as they are associated with increased patient adherence and improved BP control. Treatment with SPC has been recommended in the European Hypertension Guidelines, but optimization of the total CVD risk may need adoption of more ambitious treatment strategies aimed to deliver single pills that control multiple CVD risk factors. Amlodipine, perindopril and atorvastatin have been shown to improve BP and lipid levels to a great extent when given separately, and this combination has also been shown to improve cardiovascular outcomes. Overall, early intervention in patients with hypertension with use of an effective, high-intensity cardiovascular risk reduction regimen and attention to medication adherence through reducing pill burden are likely to result in optimal outcomes.
PubMed: 31933276
DOI: 10.1007/s40119-019-00159-1 -
Drugs in R&D Dec 2018Management of hypertension and dyslipidemia is important when considering cardiovascular disease risk; however, achievement of optimal lipid and blood pressure (BP)... (Clinical Trial)
Clinical Trial Observational Study
Post Hoc Analysis of the CONFIDENCE II, PROTECT I, SHAKE THE HABIT I and SHAKE THE HABIT II Observational Studies in Mild to Moderate Hypertensive Patients Treated with Perindopril and Atorvastatin Concomitantly.
BACKGROUND AND OBJECTIVES
Management of hypertension and dyslipidemia is important when considering cardiovascular disease risk; however, achievement of optimal lipid and blood pressure (BP) targets in clinical practice remains inadequate. This analysis sought to estimate the frequency, effectiveness, and safety of co-administrated atorvastatin and perindopril in routine care.
METHODS
We conducted a post hoc analysis of four Canadian, prospective, multi-center, observational studies assessing real-life effectiveness and safety of perindopril + atorvastatin in mild-to-moderate hypertensive patients with concomitant dyslipidemia over 16 weeks. The safety population comprised patients receiving one or more doses of free combination perindopril + atorvastatin; the full analysis set (FAS) received perindopril + atorvastatin at baseline, with one or more post-baseline systolic BP measurements while on treatment.
RESULTS
A total of 3541 and 3172 patients were included in the safety population and FAS, respectively. At the last observation carried forward, significant reductions in mean systolic BP (- 18.0 mmHg; p < 0.001) and diastolic BP (- 8.9 mmHg; p < 0.001) were observed; target BP was achieved by 73.1% of patients. Emergent adverse events (AEs) were reported in 8.0% of patients, the most common being cough (4.5% of patients), headache (0.9%), and dizziness (0.8%). Four serious AEs were reported among three (0.1%) patients. No differences were observed in effectiveness or safety between studies.
CONCLUSIONS
Concomitant perindopril + atorvastatin therapy demonstrated similar efficacy across all studies, with significant reductions in BP and achievement of target BP levels observed in a real-world setting. Results align with known safety profiles of atorvastatin and perindopril, with no unexpected AEs observed when compared with data from treatment with the individual drugs.
Topics: Administration, Oral; Aged; Antihypertensive Agents; Atorvastatin; Blood Pressure; Canada; Cohort Studies; Female; Humans; Hypertension; Male; Middle Aged; Perindopril; Prospective Studies; Treatment Outcome
PubMed: 30448890
DOI: 10.1007/s40268-018-0255-7 -
Journal of Traditional and... Sep 2023Heart failure (HF) is a complex clinical syndrome that represents the end result of several pathophysiologic processes. Despite a dramatic evolution in diagnosis and...
Xin-Li formula attenuates heart failure induced by a combination of hyperlipidemia and myocardial infarction in rats via Treg immunomodulation and NLRP3 inflammasome inhibition.
BACKGROUND AND AIM
Heart failure (HF) is a complex clinical syndrome that represents the end result of several pathophysiologic processes. Despite a dramatic evolution in diagnosis and management of HF, most patients eventually become resistant to therapy. Xin-Li Formula (XLF) is a Chinese medicine formula which shows great potential in the treatment of HF according to our previous studies. The present study was designed to investigate the effects of XLF on HF induced by a combination of hyperlipidemia and myocardial infarction (MI) in rats and reveal the underlying mechanism.
EXPERIMENTAL PROCEDURE
A rat model of HF induced by hyperlipidemia and MI was established with intragastric administration of XLF and Perindopril. In vitro, CD4 T cells from mouse spleen and LPS/ATP-stimulated THP-1 macrophages were employed.
RESULTS AND CONCLUSION
XLF was shown to have markedly protective effects on MI-induced HF with hyperlipidemia in rats, including improvement of left ventricular function, reduction of left ventricular fibrosis and infarct size. Moreover, XLF administration significantly increased the number of Foxp3 Tregs, and inhibited mTOR phosphorylation and NLRP3 signaling pathway. In vitro, we found that XLF had induced Treg activation via the inhibition of mTOR phosphorylation in CD4 T cells. Additionally, XLF inhibited NLRP3 inflammasome activation in LPS/ATP-stimulated THP-1 macrophages. Taken together, this study raises the exciting possibility that Xin-Li Formula may benefit HF patients due to its immunomodulatory and anti-inflammatory effects via Treg activation and NLRP3 inflammasome inhibition.
PubMed: 37693100
DOI: 10.1016/j.jtcme.2023.03.009 -
Revue Medicale de Liege May 2017In patients suffering from systemic arterial hypertension, coronary artery disease, or heart failure, beta-blockers and angiotensin-convertase enzyme inhibitors play a... (Review)
Review
In patients suffering from systemic arterial hypertension, coronary artery disease, or heart failure, beta-blockers and angiotensin-convertase enzyme inhibitors play a major therapeutic and preventive role. Coronary artery disease remains the leading cause of mortality in industrialized countries. Unless adapted preventive strategy, notably pharmacological interventions, cardiovascular events in these patients remain high. One reason for this relative failure is represented by non-adherence to treatment. A treatment consisting in an association in one pill of several different molecules should confer a higher treatment compliance and thus efficacy. This article describes the characteristics of the first available dual association between a cardioselective beta-blocker agent, bisoprolol, and an angiotensin-convertase enzyme inhibitor, perindopril arginine.
Topics: Antihypertensive Agents; Bisoprolol; Drug Combinations; Humans; Perindopril
PubMed: 28520326
DOI: No ID Found -
Annals of Medicine and Surgery (2012) Aug 2023Wunderlich syndrome is a rare and life-threatening condition that is characterized by spontaneous renal hemorrhage into the subcapsular and perinephric regions. This...
UNLABELLED
Wunderlich syndrome is a rare and life-threatening condition that is characterized by spontaneous renal hemorrhage into the subcapsular and perinephric regions. This case report describes the diagnosis and management of bilateral Wunderlich syndrome during pregnancy, resulting in Page kidney.
CASE PRESENTATION
The patient presented with complaints of left flank pain and breathlessness. After stabilization, an emergency lower cesarean delivery was performed, and a percutaneous drainage procedure was carried out to alleviate the compression on the left kidney. The patient was treated with blood transfusion, methyldopa, and perindopril. Follow-up examinations performed 3 months later revealed a significant decrease in fluid volume surrounding the left kidney.
CLINICAL DISCUSSION
Lenk's triad provides the primary description of the classical manifestations of this syndrome. Some instances have been connected to the Page kidney phenomenon. The relationship between pregnancy and Wunderlich syndrome has not been extensively studied, primarily because the symptoms can resemble other complications related to pregnancy. Due to the scarcity of evidence in the literature, there is no definitive guideline for managing Wunderlich syndrome during pregnancy. Consequently, each patient is treated on an individual basis. Conservative treatment is recommended once malignancy has been ruled out.
CONCLUSION
The case highlights the importance of considering Wunderlich syndrome as a differential diagnosis in pregnant patients with abdominal or flank pain, a palpable mass, and hypovolemia. Furthermore, the case illustrates the successful management of Wunderlich syndrome during pregnancy.
PubMed: 37554856
DOI: 10.1097/MS9.0000000000001062