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European Journal of Internal Medicine Apr 2023Angiotensin converting enzyme inhibitors (ACEi) have consistently demonstrated improved survival and reduced risk of major cardiovascular events, across the spectrum of... (Review)
Review
Angiotensin converting enzyme inhibitors (ACEi) have consistently demonstrated improved survival and reduced risk of major cardiovascular events, across the spectrum of cardiovascular disease, including hypertension, coronary artery disease, myocardial infarction, and heart failure. The cardioprotective effects of ACEi result from inhibiting the conversion of angiotensin I to angiotensin II, and inhibition of bradykinin degradation. They are generally well tolerated but may cause the onset of a dry cough in some patients. This review presents current evidence on the incidence and mechanisms of cough associated with ACEi use, and then considers how to manage ACEi-related cough in clinical practice. The incidence of ACEi-induced cough in the published literature varies widely due to heterogeneity in the source data and lack of adequate controls. Incidence also varies among individual ACEi with agents such as perindopril, which has a high tissue ACE affinity, associated with a lower rate of cough. Evidence from real-world studies shows that the incidence of ACEi-associated cough is lower than rates reported in clinical trials. Patients who experience any dry cough are often switched to angiotensin- receptor blockers or other classes of antihypertensive drugs, regardless of cough severity. To avoid inappropriate discontinuation of ACEi in clinical practice, an alternative approach in patients with persistent cough is to perform a challenge/re-challenge to determine if re-introduction of ACEi is associated with recurrence of symptoms. Incidence of cough should not be considered a class effect for ACEi, and the patient may benefit by a switch from one ACEi to another. Every effort should be made to enable patients to continue ACEi therapy to reduce adverse cardiovascular outcomes and improve survival.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Cough; Antihypertensive Agents; Hypertension; Angiotensin Receptor Antagonists; Myocardial Infarction
PubMed: 36628825
DOI: 10.1016/j.ejim.2023.01.005 -
Jornal Vascular Brasileiro 2022The prevalence of coronary artery anomalies has been increasing due to the increasing usage of coronary angiography. There is a paucity of literature concerning...
The prevalence of coronary artery anomalies has been increasing due to the increasing usage of coronary angiography. There is a paucity of literature concerning management of viral-induced myocarditis in patients with anomalous coronary artery. We present a very unusual case of a 44-year-old man with anomalous origin of the left circumflex artery from the proximal ostium of the right coronary artery who was admitted for COVID-19-induced myocarditis. He presented with signs of heart failure and coronary angiography revealed the left circumflex artery with a separate ostium originating from the proximal right coronary artery. He was treated medically with Bisoprolol, Perindopril Arginine, Rivaroxaban, and Furosemide. His condition improved rapidly and he resumed regular life within 1 month. Coexistence of cardiac disease such as viral-induced myocarditis with an underlying anomalous origin of the coronary artery is challenging to spot and can lead to worse outcomes in case of misdiagnosis and inaccurate management.
PubMed: 36544985
DOI: 10.1590/1677-5449.202102132 -
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 -
Cardiovascular Drugs and Therapy Feb 2024To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy.
The Effects of a Perindopril-Based Regimen in Relation to Statin Use on the Outcomes of Patients with Vascular Disease: a Combined Analysis of the ADVANCE, EUROPA, and PROGRESS Trials.
PURPOSE
To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy.
METHODS
A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use.
RESULTS
At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77-0.98) and non-statin users (aHR 0.80, 95% CI 0.74-0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant.
CONCLUSION
Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use.
Topics: Humans; Perindopril; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Treatment Outcome; Stroke
PubMed: 36194352
DOI: 10.1007/s10557-022-07384-2 -
Saudi Pharmaceutical Journal : SPJ :... Aug 2022Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. The major challenge in managing HCC is the resistance to chemotherapy. Leptin...
UNLABELLED
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. The major challenge in managing HCC is the resistance to chemotherapy. Leptin hormone is associated with different oncogenic pathways implicated in drug resistance. Angiotensin II was found to decrease the production and secretion of leptin.
OBJECTIVE
This study investigated the potential role of an ACEI perindopril as a chemosensitizer agent to sorafenib.
METHOD
HCC was induced in mice using a single dose of diethylnitrosamine DENA (200 mg/kg) followed by phenobarbital 0.05% in drinking water for 16 weeks. Mice were then treated with perindopril (1 mg/kg/day), Sorafenib (30 mg/kg/day), or both of them for another four weeks. Leptin, VEGF, MMP-9, Cyclin D1, EpCAM, and β-catenin were measured using immunoassay while Wnt and ALDH1 were assayed using western blotting assay.
RESULTS
Perindopril whether alone or in combination with sorafenib decrease liver enzymes and preserve the liver architecture. Our study revealed that perindopril significantly increased the antineoplastic, antiangiogenic as well as anti-metastatic effects of sorafenib. This effect was correlated with the downregulation of the leptin / Wnt / β-catenin pathway and overexpression of ALDH1 while downregulation of EpCAM.
CONCLUSION
This study presents perindopril as a potential chemosensitizer agent that works through decreased expression of the leptin / Wnt / β-catenin pathway.
PubMed: 36164573
DOI: 10.1016/j.jsps.2022.06.019 -
Hypertension (Dallas, Tex. : 1979) Nov 2022The effect of 3 commonly recommended combinations of anti-hypertensive agents-amlodipine plus hydrochlorothiazide (calcium channel blocker [CCB]+thiazide), amlodipine... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The effect of 3 commonly recommended combinations of anti-hypertensive agents-amlodipine plus hydrochlorothiazide (calcium channel blocker [CCB]+thiazide), amlodipine plus perindopril (CCB+ACE [angiotensin-converting enzyme]-inhibitor), and perindopril plus hydrochlorothiazide (ACE-inhibitor+thiazide) on blood pressure variability (V) are unknown.
METHODS
We calculated the blood pressure variability (BPV) in 405 patients (130, 146, and 129 randomized to ACE-inhibitor+thiazide, CCB+thiazide, and CCB+ACE-inhibitor, respectively) who underwent ambulatory blood pressure monitoring after 6 months of treatment in the Comparisons of Three Combinations Therapies in Lowering Blood Pressure in Black Africans trial (CREOLE) of Black African patients. BPV was calculated using the SD of 30-minute interval values for 24-hour ambulatory BPs and for confirmation using the coefficient of variation. Linear mixed model regression was used to calculate mean differences in BPV between treatment arms. Within-clinic BPV was also calculated from the mean SD and coefficient of variation of 3 readings at clinic visits.
RESULTS
Baseline distributions of age, sex, and blood pressure parameters were similar across treatment groups. Participants were predominately male (62.2%) with mean age 50.4 years. Those taking CCB+thiazide had significantly reduced ambulatory systolic and diastolic BPV compared with those taking ACE-inhibitor+thiazide. The CCB+thiazide and CCB+ACE-inhibitor groups showed similar BPV. Similar patterns of BPV were apparent among groups using within-clinic blood pressures and when assessed by coefficient of variation.
CONCLUSIONS
Compared with CCB-containing combinations, ACE-inhibitor plus thiazide was associated with higher levels, generally significant, of ambulatory and within-clinic systolic and diastolic BPV. These results supplement the differential ambulatory blood pressure-lowering effects of these therapies in the CREOLE trial.
Topics: Humans; Male; Middle Aged; Perindopril; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Hypertension; Drug Therapy, Combination; Amlodipine; Hydrochlorothiazide; Calcium Channel Blockers; Drug Combinations; Thiazides; Angiotensin-Converting Enzyme Inhibitors
PubMed: 36052684
DOI: 10.1161/HYPERTENSIONAHA.121.18333 -
Cureus Jul 2022The effect of antihypertensive drugs, especially drugs modulating the renin-angiotensin-aldosterone-system (RAAS), on neurodegenerative diseases still needs to be...
The effect of antihypertensive drugs, especially drugs modulating the renin-angiotensin-aldosterone-system (RAAS), on neurodegenerative diseases still needs to be investigated. This study aimed to compare the effects of three different antihypertensive drugs (telmisartan, perindopril, and nebivolol) on neuroprotection and acetylcholine (ACh) levels against lipopolysaccharide (LPS)-induced injury in a differentiated SH-SY5Y cell line. Cells were treated with retinoic acid for differentiation to a neuronal phenotype. LPS 20 (μg/mL) was applied to the cells for one hour. Then, the cells were treated with 1, 5, and 10 µg/mL concentrations of telmisartan, perindopril, and nebivolol separately for 24 hours, except for the control and LPS alone groups. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ACh levels were analyzed using an enzyme immunosorbent assay in the culture medium. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) expressions were evaluated using western blot analysis. Telmisartan demonstrated the highest cell viability against LPS-induced injury, whereas the protective effect of perindopril was moderate. Nebivolol showed no neuroprotective effect. The protective effect of 10-µg/mL telmisartan was superior to 10 µg/mL perindopril (p=0.006), 5 µg/mL perindopril (p=0.001), 1 µg/mL perindopril (p=0.001), and 1, 5, and 10 µg/mL nebivolol (p<0.001). Among all the study drugs, only telmisartan provided a statistically significant increase in ACh levels after LPS-induced injury. Additionally, the administration of telmisartan provided a concentration-dependent reduction in TNF-α, IL-1β, and NFκB expression against LPS-induced neuroinflammation. These findings suggest that telmisartan has a superior neuroprotective effect against LPS-induced injury in neuron-like cells compared with both perindopril and nebivolol.
PubMed: 36051740
DOI: 10.7759/cureus.27429 -
International Journal of Environmental... Aug 2022The use of international nonproprietary names (INNs) has been mandatory for prescriptions of state-reimbursed drugs in Latvia since 1 April 2020. In a retrospective...
The use of international nonproprietary names (INNs) has been mandatory for prescriptions of state-reimbursed drugs in Latvia since 1 April 2020. In a retrospective analysis, we aimed to examine the impact of the new regulation on changes in the prescribing and dispensing practice of antihypertensive agents with an example of bisoprolol or/and perindopril and their combinations. All state-reimbursed bisoprolol and/or perindopril prescriptions for arterial hypertension were evaluated in two time periods: 1 April 2018 to 31 March 2019 and 1 April 2020 to 31 March 2021. The proportion of INN prescriptions increased from 2.1% to 92.3% (p < 0.001, φ = 0.903). The rate of fixed-dose combinations (FDCs) increased from 60.8% to 66.5% (p < 0.001, φ = 0.059). The rate of medication errors was 0.6%. The most common (80.6%) error was that the dispensed medicine dose was larger or smaller than indicated on the prescription. In addition, prescribing an FDC medicine increased the chance of making an error by 2.5 times on average. Regulatory changes dramatically affected the medicine-prescribing habits of INNs. The increase in FDC prescription rates may align with the recommendations of the 2018 ESC/ESH guidelines. The proportion of total errors is estimated as low, but control mechanisms are needed to prevent them.
Topics: Bisoprolol; Humans; Hypertension; Latvia; Medication Errors; Perindopril; Retrospective Studies
PubMed: 36011791
DOI: 10.3390/ijerph191610156 -
Clinical Journal of the American... Aug 2022Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes. However, whether to continue or discontinue the drug after hyperkalemia remains unclear.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Data came from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, which included a run-in period where all participants initiated angiotensin-converting enzyme inhibitor-based therapy (a fixed combination of perindopril and indapamide). The study population was taken as patients with type 2 diabetes with normokalemia (serum potassium of 3.5 to <5.0 mEq/L) at the start of run-in. Potassium was remeasured 3 weeks later when a total of 9694 participants were classified into hyperkalemia (≥5.0 mEq/L), normokalemia, and hypokalemia (<3.5 mEq/L) groups. After run-in, patients were randomized to continuation of the angiotensin-converting enzyme inhibitor-based therapy or placebo; major macrovascular, microvascular, and mortality outcomes were analyzed using Cox regression during the following 4.4 years (median).
RESULTS
During active run-in, 556 (6%) participants experienced hyperkalemia. During follow-up, 1505 participants experienced the primary composite outcome of major macrovascular and microvascular events. Randomized treatment of angiotensin-converting enzyme inhibitor-based therapy significantly decreased the risk of the primary outcome (38.1 versus 42.0 per 1000 person-years; hazard ratio, 0.91; 95% confidence interval, 0.83 to 1.00; =0.04) compared with placebo. The magnitude of effects did not differ across subgroups defined by short-term changes in serum potassium during run-in ( for heterogeneity =0.66). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, major coronary events, major cerebrovascular events, and new or worsening nephropathy ( for heterogeneity ≥0.27).
CONCLUSIONS
Continuation of angiotensin-converting enzyme inhibitor-based therapy consistently decreased the subsequent risk of clinical outcomes, including cardiovascular and kidney outcomes and death, regardless of short-term changes in serum potassium.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), NCT00145925.
Topics: Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Gliclazide; Humans; Hyperkalemia; Potassium; Vascular Diseases
PubMed: 35896277
DOI: 10.2215/CJN.00180122