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Biomedical Papers of the Medical... Sep 2022Sub-analysis of a retrospective nation-wide observational analysis of heart failure (HF) epidemiology reported to the Czech National Registry of Reimbursed Health... (Observational Study)
Observational Study
Angiotensin-converting enzyme inhibitors, angiotensin-II-receptor antagonists and angiotensin-receptor blocker/neprilysin inhibitor utilization in heart failure patients: Sub-analysis of a nation-wide population-based study in the Czech Republic.
AIMS
Sub-analysis of a retrospective nation-wide observational analysis of heart failure (HF) epidemiology reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018 aimed at angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II-receptor antagonists (ARB) and angiotensin receptor blocker/neprilysin inhibitor (ARNI) use.
METHODS AND RESULTS
ACEi and ARBs were generally used in 87.6% of all HF patients in 2012 (n=154 627); 84.5% in 2013 (n=170 861); 83.5% in 2014 (n=186 963); 81.6% in 2015 (n=198 844); 80.1% in 2016 (n=205 793); 78.0% in 2017 (n=212 152) and in 76.7% in 2018 (n=219 235). In a sub-analysis of patients with a medical procedure and/or examination using an I50.x ICD code accounted for in the given year, ACEi and ARBs were generally used in 99.3% in 2012 (n=63 250); 96% in 2013 (n=62 241); 95.2% in 2014 (n=64 414); 93.3% in 2015 (n=65 217); 91.8% in 2016 (n=65 236); 90.1% in 2017 (n=65 761) and in 88.6% in 2018 (n=66 332). In 2018, the majority of patients with HF were prescribed ramipril (n=49 909; 17.5%) and perindopril (n=44 332; 15.5%). The mostly prescribed ARBs in 2018 were telmisartan (n=18 669; 6.5%); losartan (n=13 935; 4.9%) and valsartan (n=4 849; 1.7%). In 24.5% of cases, ACEIs and ARBs were prescribed in a fixed combination with another drug. ARNI became gradually more prescribed from 2018 (n=9 659 in November 2020).
CONCLUSION
In an analysis of ACEIs, ARBs and ARNIs utilization in all patients treated for heart failure in the given year in the whole country, we found a comparable rate of drug prescription in comparison with specific heart failure registries. This indicates a good translation of current standard of care into common clinical practice. Ramipril and perindopril remained the mostly prescribed ACEIs and telmisartan became the mostly prescribed ARB. Since 2018, ARNIs began to be widely prescribed.
Topics: Angiotensin II Type 2 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Antihypertensive Agents; Czech Republic; Heart Failure; Humans; Losartan; Neprilysin; Perindopril; Ramipril; Retrospective Studies; Telmisartan; Valsartan
PubMed: 34092792
DOI: 10.5507/bp.2021.035 -
JAMA Cardiology Nov 2023The US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection...
IMPORTANCE
The US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (EF) to all patients with HF, noting the greatest benefits in those with below-normal EF. However, the upper bound of below normal is not clearly defined, and value determinations across a broader EF range are unknown.
OBJECTIVE
To estimate the cost-effectiveness of sacubitril-valsartan vs renin-angiotensin system inhibitors (RASis) across various upper-level cutoffs of EF.
DESIGN, SETTING, AND PARTICIPANTS
This economic evaluation included participant-level data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and the PARAGON-HF (Prospective Comparison of ARNi with ARB Global Outcomes in HF With Preserved Ejection Fraction) trials. PARADIGM-HF was conducted between 2009 and 2014, PARAGON-HF was conducted between 2014 and 2019, and this analysis was conducted between 2021 and 2023.
MAIN OUTCOMES AND MEASURES
A 5-state Markov model used risk reductions for all-cause mortality and HF hospitalization from PARADIGM-HF and PARAGON-HF. Quality-of-life differences were estimated from EuroQol-5D scores. Hospitalization and medication costs were obtained from published national sources; the wholesale acquisition cost of sacubitril-valsartan was $7092 per year. Risk estimates and treatment effects were generated in consecutive 5% EF increments up to 60% and applied to an EF distribution of US patients with HF from the Get With the Guidelines-Heart Failure registry. The base case included a lifetime horizon from a health care sector perspective. Incremental cost-effectiveness ratios (ICERs) were estimated at EFs of 60% or less (base case) and at various upper-level EF cutoffs.
RESULTS
Among 13 264 total patients whose data were analyzed, for those with EFs of 60% or less, sacubitril-valsartan was projected to add 0.53 quality-adjusted life-years (QALYs) at an incremental lifetime cost of $40 892 compared with RASi, yielding an ICER of $76 852 per QALY. In a probabilistic sensitivity analysis, 95% of the values of the ICER occurred between $71 516 and $82 970 per QALY. Among patients with chronic HF and an EF of 60% or less, treatment with sacubitril-valsartan vs RASis would be at least of economic intermediate value (ICER <$180 000 per QALY) at a sacubitril-valsartan cost of $10 242 or less per year, of high economic value (ICER <$60 000 per QALY) at a cost of $3673 or less per year, and cost-saving at a cost of $338 or less per year. The ICERs were $67 331 per QALY, $59 614 per QALY, and $56 786 per QALY at EFs of 55% or less, 50% or less, and 45% or less, respectively. Treatment with sacubitril-valsartan in only those with EFs of 45% or greater (up to ≤60%) yielded an ICER of $127 172 per QALY gained; treatment was more cost-effective in those at the lower end of this range (ICER of $100 388 per QALY gained for those with EFs of 45%-55%; ICER of $84 291 per QALY gained for those with EFs of 45%-50%).
CONCLUSIONS AND RELEVANCE
Cost-effectiveness modeling provided an ICER for treatment with sacubitril-valsartan vs RASis consistent with high economic value for patients with reduced and mildly reduced EFs (≤50%) and at least intermediate value at the current undiscounted wholesale acquisition cost price at an EF of 60% or less. Treatment was more cost-effective at lower EF ranges. These findings may have implications for coverage decisions and value assessments in contemporary clinical practice guidelines.
Topics: United States; Humans; Cost-Benefit Analysis; Neprilysin; Angiotensins; Stroke Volume; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Tetrazoles; Heart Failure; Antihypertensive Agents
PubMed: 37755814
DOI: 10.1001/jamacardio.2023.3216 -
Journal of Clinical Hypertension... May 2021Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more... (Meta-Analysis)
Meta-Analysis
Is the newest angiotensin-receptor blocker azilsartan medoxomil more efficacious in lowering blood pressure than the older ones? A systematic review and network meta-analysis.
Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more effective than the older ones. A network meta-analysis was performed to compare the efficacy of various angiotensin-receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin-receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6-12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20-80 mg), irbesartan (300 mg), olmesartan (20-40 mg), telmisartan (80 mg), and valsartan (160-320 mg), but not candesartan (8-16 mg), losartan (50-100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24-hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin-receptor blockers had different blood pressure lowering efficacy. The newest angiotensin-receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensins; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Network Meta-Analysis; Olmesartan Medoxomil; Oxadiazoles; Tetrazoles
PubMed: 33609077
DOI: 10.1111/jch.14227 -
Journal of Microbiology and... Sep 2022The placenta is a captivating multifunctional organ of fetal origin and plays an essential role during pregnancy by intimately connecting mother and baby. This study...
The placenta is a captivating multifunctional organ of fetal origin and plays an essential role during pregnancy by intimately connecting mother and baby. This study explicates placental pathology and information about 25 placentas collected from the mothers infected with novel coronavirus (SARS-COV-2). So far, congenital transmission of SARS-CoV-2 seems to be remarkably uncommon in spite of many cases of COVID-19 during pregnancy. Out of the 25 placental tissue samples collected, none has shown gene expression of SARS-CoV-2 when confirmed by RT-PCR. At the same time, nasal and throat swab samples collected from newborns of SARS-CoV-2-positive mothers correspondingly tested negative by RT-PCR. The shielding properties of placental barriers against viral infections from mothers to newborns remains a mystery. Major histopathological findings have been recorded as choriodecidual tissue with necrosis, intramural fibrin deposition, chorionic villi with fibrosis, and calcification. Moreover, although recent findings are insufficient to prove direct placental transmission of COVID-19, the abundance of angiotensin-converting enzymes-2 (ACE-2) on the placental surface could potentially contribute to unpleasant outcomes during pregnancy as SARSCoV-2 gains access to human cells via ACE-2. Finally, the significance of these findings is vague and needs further study.
Topics: Angiotensins; COVID-19; Female; Fibrin; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Mothers; Placenta; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2
PubMed: 36039383
DOI: 10.4014/jmb.2206.06056 -
Genetics Research 2023Health and economies are both affected by the coronavirus disease-19 (COVID-19) global pandemic. Angiotensin-converting enzyme 2 () is a polymorphic enzyme that is a...
BACKGROUND
Health and economies are both affected by the coronavirus disease-19 (COVID-19) global pandemic. Angiotensin-converting enzyme 2 () is a polymorphic enzyme that is a part of the renin-angiotensin system, and it plays a crucial role in viral entry. Previous investigations and studies revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have a considerable association. Recently, variants have been described in human populations in association with cardiovascular and pulmonary conditions. In this study, genetic susceptibility to COVID-19 in different populations was investigated.
METHODS AND RESULTS
We evaluated the identified variants based on the predictive performance of 5 deleteriousness-scoring methods and the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. The results indicated 299 variants within the gene. The variants were analyzed by different analysis tools to assess their functional effects. Ultimately, 5 more deleterious variants were found in the gene.
CONCLUSIONS
Collecting more information about the variations in binding affinity between SARS-CoV-2 and host-cell receptors due to variants leads to progress in treatment strategies for COVID-19. The evidence accumulated in this study showed that variants in different populations may be associated with the genetic susceptibility, symptoms, and outcome of SARS-CoV-2 infection.
Topics: Humans; Angiotensin-Converting Enzyme 2; Angiotensins; COVID-19; Genetic Predisposition to Disease; Genetic Variation; SARS-CoV-2
PubMed: 38074420
DOI: 10.1155/2023/2593199 -
Fundamental & Clinical Pharmacology Feb 2021
Outcome of patients hospitalized for Covid-19 and exposure to angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in France: Results of the ACECoV study.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; COVID-19; France; Humans; Hypertension; SARS-CoV-2
PubMed: 33290594
DOI: 10.1111/fcp.12637 -
Journal of the European Academy of... Mar 2020Systemic sclerosis (SSc) is a multisystemic disease with an extensive microvasculopathy. Previously, disturbances in plasma levels of angiotensin II (Ang II) and its...
BACKGROUND
Systemic sclerosis (SSc) is a multisystemic disease with an extensive microvasculopathy. Previously, disturbances in plasma levels of angiotensin II (Ang II) and its antagonistic angiotensin-(1-7) (Ang-(1-7)) were found in patients with SSc. Their significance in a pathogenesis of SSc stays unclear due to discrepancies of earlier studies.
OBJECTIVES
To evaluate a significance of disturbances in production pathway of angiotensins in a development of SSc.
METHODS
There were enrolled 27 patients with established SSc, 23 subjects with very early SSc and 23 healthy controls. The diagnosis of SSc was established in patients who met EULAR/ACR 2013 classification criteria. Very early SSc described patients with Raynaud's phenomenon having SSc-specific antinuclear antibodies and SSc-like abnormalities in nailfold videocapillaroscopy. Patients were submitted to evaluation of internal organ involvement and blood sampling to assay plasma levels of angiotensin I, angiotensin II and angiotensin-(1-7) with ELISA technique.
RESULTS
Plasma level of angiotensin-(1-7) was significantly reduced in both SSc group (median = 47.2 pg/mL; P < 0.001) and ones with very early SSc (median = 102.7 pg/mL; P = 0.002) when compared to healthy controls (median = 176.1 pg/mL). A tendency to higher than in control group (median = 214 pg/mL) plasma level of angiotensin I was seen in SSc group (median = 392 pg/mL; P = 0.059). Differences in plasma level of angiotensin II were insignificant between all study groups. Those disturbances produced unfavourable angiotensin-(1-7)/angiotensin II (%) ratio in both groups of patients, which achieved statistical significance in subjects with established SSc (P < 0.001). Production pathway of angiotensins showed a dependence on a subtype of SSc, immune profile and a presence of interstitial lung disease.
CONCLUSIONS
Production of angiotensin-(1-7) was significantly reduced in both SSc patients and those ones with very early SSc, although a significant imbalance between angiotensin II and angiotensin-(1-7) occurred only in subjects with established disease.
Topics: Adult; Aged; Angiotensin I; Angiotensin II; Female; Humans; Male; Middle Aged; Peptide Fragments; Scleroderma, Systemic; Young Adult
PubMed: 31746507
DOI: 10.1111/jdv.16103 -
Arteriosclerosis, Thrombosis, and... Dec 2023Blood pressure management involves antihypertensive therapies blocking the renin-angiotensin system (RAS). Yet, it might be inadequate due to poor patient adherence or... (Review)
Review
Blood pressure management involves antihypertensive therapies blocking the renin-angiotensin system (RAS). Yet, it might be inadequate due to poor patient adherence or the so-called RAS escape phenomenon, elicited by the compensatory renin elevation upon RAS blockade. Recently, evidence points toward targeting hepatic AGT (angiotensinogen) as a novel approach to block the RAS pathway that could circumvent the RAS escape phenomenon. Removing AGT, from which all angiotensins originate, should prevent further angiotensin generation, even when renin rises. Furthermore, by making use of a trivalent -acetylgalactosamine ligand-conjugated small interfering RNA that specifically targets the degradation of hepatocyte-produced mRNAs in a highly potent and specific manner, it may be possible in the future to manage hypertension with therapy that is administered 1 to 2× per year, thereby supporting medication adherence. This review summarizes all current findings on AGT small interfering RNA in preclinical models, making a comparison versus classical RAS blockade with either ACE (angiotensin-converting enzyme) inhibitors or AT1 (angiotensin II type 1) receptor antagonists and AGT suppression with antisense oligonucleotides. It ends with discussing the first-in-human study with AGT small interfering RNA.
Topics: Humans; Acetylgalactosamine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Blood Pressure; Hypertension; Renin; Renin-Angiotensin System; RNA, Small Interfering
PubMed: 37855126
DOI: 10.1161/ATVBAHA.123.319897 -
Biology of Sex Differences Jul 2019Obesity is a global epidemic that greatly increases risk for developing cardiovascular disease and type II diabetes. Sex differences in the obese phenotype are well... (Review)
Review
Obesity is a global epidemic that greatly increases risk for developing cardiovascular disease and type II diabetes. Sex differences in the obese phenotype are well established in experimental animal models and clinical populations. While having higher adiposity and obesity prevalence, females are generally protected from obesity-related metabolic and cardiovascular complications. This protection is, at least in part, attributed to sex differences in metabolic effects of hormonal mediators such as the renin-angiotensin system (RAS). Previous literature has predominantly focused on the vasoconstrictor arm of the RAS and shown that, in contrast to male rodent models of obesity and diabetes, females are protected from metabolic and cardiovascular derangements produced by angiotensinogen, renin, and angiotensin II. A vasodilator arm of the RAS has more recently emerged which includes angiotensin-(1-7), angiotensin-converting enzyme 2 (ACE2), mas receptors, and alamandine. While accumulating evidence suggests that activation of components of this counter-regulatory axis produces positive effects on glucose homeostasis, lipid metabolism, and energy balance in male animal models, female comparison studies and clinical data related to metabolic outcomes are lacking. This review will summarize current knowledge of sex differences in metabolic effects of the RAS, focusing on interactions with gonadal hormones and potential clinical implications.
Topics: Angiotensins; Animals; Female; Gonadal Steroid Hormones; Humans; Male; Receptors, Angiotensin; Renin; Renin-Angiotensin System; Sex Characteristics
PubMed: 31262355
DOI: 10.1186/s13293-019-0247-5 -
European Journal of Clinical... Apr 2023Hypertension management in older patients represents a challenge, particularly when hospitalized. (Observational Study)
Observational Study
BACKGROUND
Hypertension management in older patients represents a challenge, particularly when hospitalized.
OBJECTIVE
The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients.
METHODS
A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge.
RESULTS
Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death.
CONCLUSIONS
Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.
Topics: Aged; Aged, 80 and over; Humans; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Antihypertensive Agents; Calcium Channel Blockers; Hypertension; Prospective Studies; Sodium Chloride Symporter Inhibitors
PubMed: 36453932
DOI: 10.1111/eci.13931