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Turkish Journal of Emergency Medicine 2021This is the first report on a case of perindopril/amlodipine-induced thrombotic microangiopathy (TMA) syndrome. A 48-year-old female was admitted complaining of nettle...
This is the first report on a case of perindopril/amlodipine-induced thrombotic microangiopathy (TMA) syndrome. A 48-year-old female was admitted complaining of nettle rash all over the body, bloody urine, and weakness shortly after starting antihypertensive therapy with perindopril/amlodipine. Shortly thereafter, she developed pronounced hemiparesis, somnolence, and sensorimotor aphasia. Laboratory findings were compatible with microangiopathic hemolytic anemia and thrombocytopenia. She was diagnosed with TMA. Cessation of perindopril/amlodipine therapy and treatment with plasma exchange and systemic corticosteroids resulted in full recovery. Very seldom perindopril/amlodipine may cause hematologic abnormalities, probably through an immunological mechanism, but there were no reports of causing TMA so far. In our case, the symptoms began shortly after the start of perindopril/amlodipine use. The clinical course of TMA in the case was compatible with TMA related to an acute, immune-mediated drug reaction. The most important thing is to promptly recognize TMA and its induction by a drug because distinctive treatment and cessation of the suspected drug can prevent severe outcome, as it was avoided in our patient.
PubMed: 33575515
DOI: 10.4103/2452-2473.301915 -
The New England Journal of Medicine May 2008Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death.
METHODS
We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.
RESULTS
The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).
CONCLUSIONS
The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).
Topics: Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypertension; Indapamide; Kaplan-Meier Estimate; Male; Perindopril; Stroke
PubMed: 18378519
DOI: 10.1056/NEJMoa0801369 -
American Journal of Cardiovascular... Mar 2022The single-pill combination (SPC) of perindopril (PER)/indapamide (IND)/amlodipine (AML) is a valuable and convenient treatment option for patients with hypertension... (Review)
Review
The single-pill combination (SPC) of perindopril (PER)/indapamide (IND)/amlodipine (AML) is a valuable and convenient treatment option for patients with hypertension controlled with two-drug SPC of PER/IND + AML given as two separate pills at the same dose level. PER [an angiotensin-converting enzyme (ACE) inhibitor], IND (a thiazide-like diuretic) and AML (a calcium channel blocker) are well established antihypertensive agents, which have been available for a long time as monotherapies and dual SPCs and have complementary mechanisms of action. Once-daily PER/IND/AML provided effective BP control, with good tolerability, in patients with uncontrolled hypertension in clinical trials and in large observational prospective studies. The efficacy and tolerability of PER/IND/AML was similar to that of PER/IND + AML in a randomized clinical trial. The therapeutic effect of PER/IND/AML was associated with improved health-related quality of life. Thus, switching from the two-pill PER/IND + AML regimen to single-pill PER/IND/AML reduces pill burden and simplifies drug administration, which may improve adherence to treatment, leading to better BP control and clinical outcomes.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Humans; Hypertension; Indapamide; Perindopril; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 35257306
DOI: 10.1007/s40256-022-00521-0 -
Materia Socio-medica Mar 2020Perindopril is a tissue-specific ACE inhibitor with 24 hours long blood pressure-lowering effect, which protects blood vessels and decreases the variability of blood...
INTRODUCTION
Perindopril is a tissue-specific ACE inhibitor with 24 hours long blood pressure-lowering effect, which protects blood vessels and decreases the variability of blood pressure.
AIM
The aim of our study was to investigate the effectiveness and safety of perindopril in newly diagnosed or previously treated but uncontrolled adult hypertensive patients.
METHODS
This prospective cohort study included primary care patients with essential hypertension. Primary study outcomes were decreasing arterial blood pressure to normal levels (<140/90 mmHg), reducing systolic arterial blood pressure for 10 mmHg or more and reducing diastolic arterial blood pressure for 5 mmHg or more. Safety was evaluated by type and frequency of adverse events.
RESULTS
In the great majority of the study patients (more than 96%) perindopril was effective as monotherapy, achieving a significant reduction in both systolic and diastolic blood pressure, and in three-quarters of the study patients it normalized both systolic and diastolic blood pressure. The effectiveness of perindopril was shown in both patients with previously and newly diagnosed hypertension, adverse events were mild and rare, even hyperkalemia was encountered less often than before the onset of the therapy with perindopril.
CONCLUSIONS
Our study confirmed excellent effectiveness of perindopril in the treatment of essential hypertension and its remarkable safety. When used as monotherapy of hypertension, perindopril's doses should be carefully titrated until the achievement of full effect, which in some patients should be awaited for at least 6 months from onset of the therapy.
PubMed: 32410885
DOI: 10.5455/msm.2020.32.4-9 -
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 -
Acta Medica Academica Dec 2022The objective of this non-interventional post-marketing clinical trial was to analyze the antihypertensive effect and safety of a fixed combination of perindopril and... (Clinical Trial)
Clinical Trial
OBJECTIVE
The objective of this non-interventional post-marketing clinical trial was to analyze the antihypertensive effect and safety of a fixed combination of perindopril and indapamide in the treatment of unregulated essential hypertension.
PATIENTS AND METHODS
The prospective clinical trial included patients aged 20 to 75 years with essential hypertension and blood pressure values ≥ 140/90 mmHg at baseline. On the basis of the investigator's decision, patients received 2 mg perindopril + 0.625 mg indapamide (group 2+0.625) or 4 mg perindopril + 1.25 mg indapamide (group 4+1.25).
RESULTS
The study included 1173 patients (426 patients in group 2+0.625 and 747 patients in group 4+1.25) at 27 investigational centers in Bosnia and Herzegovina. Mean blood pressure values at baseline and visits after nine months were significantly higher in the 4+1.25 group compared to the 2+0.625 group. There was a significant drop in systolic and diastolic blood pressure in both groups. The target values of systolic and diastolic blood pressure, according to the European Society of Cardiology (2018), were reached after nine months of therapy by more than 80% of patients in the 2+0.625 group, and this number was significantly higher compared to the 4+1.25 group where more than 60% of patients reached target values. Newly diagnosed patients had a better response to therapy. The percentage of patients receiving additional antihypertensive therapy decreased by the end of the study. Age, gender and the existence of diabetes mellitus were identified as negative predictors of target blood pressure achievement. The therapy showed a good safety profile.
CONCLUSION
A fixed combination of perindopril and indapamide was effective and safe in the treatment of unregulated essential hypertension.
Topics: Humans; Antihypertensive Agents; Blood Pressure; Drug Combinations; Essential Hypertension; Hypertension; Indapamide; Perindopril; Prospective Studies; Treatment Outcome
PubMed: 36799308
DOI: 10.5644/ama2006-124.385 -
Synergistic actions between angiotensin-converting enzyme inhibitors and statins in atherosclerosis.Nutrition, Metabolism, and... Apr 2022Hypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and... (Review)
Review
AIMS
Hypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and activating the renin-angiotensin aldosterone system (RAAS) and mevalonate pathways. This review examines how the severity and duration of these risk factors may influence the cardiovascular risk through a reciprocal interplay leading to oxidative stress and pro-inflammatory response.
DATA SYNTHESIS
The review highlights the clinical evidence supporting the benefits of statins and angiotensin-converting enzyme (ACE) inhibitors for hypertension, lipid disorders and ASCVD management, both individually and combined, at all stages of the cardiovascular continuum.
CONCLUSION
Drug strategies incorporating an ACE-inhibitor and a statin, and in particular perindopril and atorvastatin, have consistently demonstrated reductions in the rate of ASCVD events in patients with hypertension and lipid disorders, cementing their position as first-line therapies for the management of atherosclerosis complications.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Renin-Angiotensin System
PubMed: 35082055
DOI: 10.1016/j.numecd.2021.11.015 -
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