scholarly journals Angiotensin Receptor Blockers Upregulate Angiotensin Type 4 Receptor in Brains of Cognitively Intact Individuals

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 637-637
Author(s):  
Caglar Cosarderelioglu ◽  
Claudene J George ◽  
Qian-Li Xue ◽  
Esther Oh ◽  
Luigi Ferrucci ◽  
...  
Keyword(s):  
Angiotensin Receptor Blockers ◽  
Amyloid Β ◽  
Protein Carbonyl ◽  
Receptor Subtypes ◽  
Angiotensin Receptor ◽  
Older Individuals ◽  
Protein Levels ◽  
Amyloid Load ◽  
The Impact ◽  
Cognitively Intact

Abstract The primary dementia-protective benefits of Angiotensin receptor type 1 (AT1R) blockers (ARBs) are believed to arise from systemic effects on blood pressure. However, there is a brain-specific renin-angiotensin system (b-RAS) that acts mainly through three receptor subtypes: AT1R, AT2R, and AT4R. AT1R promotes inflammation and oxidative stress (OS). AT2R increases nitric oxide. AT4R is essential for dopamine release and mediates memory consolidation. Here, we aimed to investigate the effects of ARBs on b-RAS, OS, inflammation, PHF-tau, and beta-amyloid load. Postmortem frontal-cortex brains of age- and sex-matched cognitively intact (CI) individuals using (n=30) and not using ARBs (n=30) and Alzheimer's disease (AD) patients using (n=30) and not using ARBs (n=30) were studied. Protein levels of receptors were measured by Western blot. Protein carbonyl (PC) and cytokine levels were measured by ELISA. Tangle and amyloid-β scores were used as outcomes. In CI individuals, our data shows that ARB treatment was associated with higher protein levels of AT4R (median(range) 0.69(1.92) vs 0.17(1.18) CI+ARBs vs CI, p=0.02), lower level of OS marker PC (10.60(8.32) vs 11.26(7.44), CI+ARBs vs CI, p=0.03) and lower hippocampal and overall amyloid scores (0(5.45) vs 1.15(4.21) p=0.03, 0.79(12.75) vs 3.41(13.36) p=0.04, CI+ARBs vs CI, respectively). In AD group, ARB treatment was associated with lower AT1R protein levels (0.47(1.15) vs 0.59(1.99), AD+ARBs vs AD, p=0.02). No significant changes were observed in OS, inflammation, or PHF-tau and amyloid load in AD brains treated with ARBs. Our results highlight the impact of ARBs on the brains of cognitively intact and AD older individuals.

Abstract 15514: Ace Inhibitors, Angiotensin Receptor Blockers, and Outcomes in Hospitalized Patients With Severe Covid-19 Pneumonia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Prabhjot Grewal ◽  
Jeanwoo Yoo ◽  
Aikaterini Papamanoli ◽  
Azad Mojahedi ◽  
Simrat Dhaliwal ◽  
...  
Keyword(s):  
Ace Inhibitors ◽  
Cox Regression ◽  
Angiotensin Receptor Blockers ◽  
Patient Characteristics ◽  
University Hospital ◽  
Target Cells ◽  
Angiotensin Receptor ◽  
Receptor Blockers ◽  
Artery Disease ◽  
The Impact

Introduction: Angiotensin converting enzyme (ACE) 2, is a co-receptor for the entry of SARS-CoV-2 into target cells. The impact of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with coronavirus disease 19 (COVID-19) is under investigation. Hypothesis: ACEIs/ARBs are associated with worse outcomes in patients hospitalized with COVID-19. Methods: We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O2). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of previous (home) use of ACEIs or ARBs with mortality and the composite of death or MV. Results: Table 1 summarizes the patient characteristics according to ACEI/ARB use (ACEI: 73; ARB: 73; 146/469 patients, 31.1%). After a median of 13 days (8-22), 123 patients (26.2%) died and 105 patients (22.4%) required MV and survived. In models adjusting for age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, heart failure, atrial fibrillation, chronic lung disease, chronic kidney disease, and baseline 0 2 saturation, ACEIs/ARBs were not associated with mortality (HR 1.00; 95%CI 0.62-1.61; P=0.99). There was no difference between classes in mortality (ACEI vs. ARB: HR 1.14; 95%CI 0.61-2.15; P=0.68). However, there was a trend towards lower rates of death or MV with ACEI/ARB (HR 0.75; 95%CI 0.54-1.05; P=0.095), mainly because of lower MV rates. The protective effect of ARBs on the composite was significant (HR 0.66; 95%CI 0.44-0.99; P=0.046) whereas that of ACEIs was not (HR 0.87; 95%CI 0.57-1.31; P=0.50), albeit difference was not significant (P=0.28). Conclusions: In patients with severe COVID-19 pneumonia, ACEI/ARB use was not associated with mortality. Especially ARBs may reduce need for MV in this high-risk COVID-19 population.

scholarly journals SARS-CoV-2 infection and adverse outcomes in users of ACE inhibitors and angiotensin-receptor blockers: a nationwide case-control and cohort analysis

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215768 ◽  
Author(s):  
Christian Fynbo Christiansen ◽  
Anton Pottegård ◽  
Uffe Heide-Jørgensen ◽  
Jacob Bodilsen ◽  
Ole Schmeltz Søgaard ◽  
...  
Keyword(s):  
Angiotensin Receptor Blockers ◽  
Cohort Analysis ◽  
Case Control ◽  
Adverse Outcomes ◽  
Angiotensin Receptor ◽  
Current Recommendation ◽  
Icu Admission ◽  
Registration Number ◽  
Receptor Blockers ◽  
The Impact

ObjectiveTo examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes.MethodsThis nationwide case-control and cohort study included all individuals in Denmark tested for SARS-CoV-2 RNA with PCR from 27 February 2020 to 26 July 2020. We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use.ResultsThe study included 13 501 SARS-CoV-2 PCR-positive and 1 088 695 PCR-negative individuals. Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09).Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). The associations were similar when ACE-I/ARB users were compared with non-users.ConclusionsACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic.Trial registration numberEUPAS34887

scholarly journals The impact of angiotensin receptor blockers on arterial stiffness: a meta-analysis

2015 ◽  
Vol 38 (9) ◽  
pp. 613-620 ◽  
Author(s):  
Feng Peng ◽  
Hongming Pan ◽  
Bin Wang ◽  
Jinxiu Lin ◽  
Wenquan Niu
Keyword(s):  
Arterial Stiffness ◽  
Angiotensin Receptor Blockers ◽  
Meta Analysis ◽  
Angiotensin Receptor ◽  
Receptor Blockers ◽  
The Impact

Impact of Clinical Audit on Adherence to the Guidelines Directed Medical Therapy in Patients Admitted with Heart Failure

2020 ◽  
Vol 15 (2) ◽  
pp. 117-123
Author(s):  
Aashiq A. Shukkoor ◽  
Nimmy E. George ◽  
Shanmugasundaram Radhakrishnan ◽  
Sivakumar Velusamy ◽  
Tamilarasu kaliappan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Acute Heart Failure ◽  
Medical Therapy ◽  
Clinical Audit ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Receptor ◽  
Converting Enzyme Inhibitors ◽  
Reduced Ejection Fraction ◽  
The Impact

Background: The adoption of guideline recommendations of pharmacotherapy to improve the clinical course of Heart Failure (HF) remains below par. Our objective is to evaluate the impact of clinical audit on adherence to the Guideline-Directed Medical Therapy (GDMT) in patients admitted with acute heart failure with reduced ejection fraction (EF). Methods: A prospective interventional study was conducted over a period of 12 months from June 2018 to May 2019 in all patients admitted with acute heart failure with reduced ejection fraction. The discharge prescriptions of patients who met the inclusion criteria were audited for appropriateness in the usage of neurohormonal blockers and Ivabradine, by a clinical pharmacist on a monthly basis. Audit results were presented to the practicing physicians every month and feedback was given. Results: Discharge prescriptions of 716 patients who presented with HF were audited for the reasonable or unreasonable omission of neurohormonal blocking drugs. The first-month audit revealed that the unreasonable omission of Angiotensin-Converting Enzyme Inhibitors/ Angiotensin Receptor Blockers/ Angiotensin Receptor Neprilisin Inhibitors ( ACEI/ARB/ARNI), Betablockers and Mineralocorticoid Receptor Antagonists (MRA) were 24.5%, 13.1%, and 9.09% respectively, which reduced to nil at the end of the study period (p=0.00). Initiation of Ivabradine before prescribing or achieving the target dose of Betablocker was noted in 38.18% of patients in the first month, which was also reduced to nil (p=0.00) at the end of the study. Conclusion: This study reveals that periodic clinical audit improves adherence to GDMT in patients admitted with heart failure with reduced ejection fraction.

scholarly journals Association of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease‐19

2021 ◽  
Author(s):  
Rohan Khera ◽  
Callahan Clark ◽  
Yuan Lu ◽  
Yinglong Guo ◽  
Sheng Ren ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Hospital Mortality ◽  
Ace Inhibitors ◽  
Validation Cohort ◽  
Angiotensin Receptor Blockers ◽  
Study Cohort ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Older Individuals ◽  
Receptor Blockers

Abstract Background Despite its clinical significance, the risk of severe infection requiring hospitalization among outpatients with SARS‐CoV‐2 infection who receive angiotensin‐converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) remains uncertain. Methods and Results In a propensity score‐matched outpatient cohort (January – May 2020) of 2,263 Medicare Advantage and commercially insured individuals with hypertension and a positive outpatient SARS‐CoV‐2 test, we determined the association of ACE inhibitors and ARBs with COVID‐19 hospitalization. In a concurrent inpatient cohort of 7,933 hospitalized with COVID‐19, we tested their association with in‐hospital mortality. The robustness of the observations was assessed in a contemporary cohort (May – August). In the outpatient study, neither ACE inhibitors (HR, 0.77, 0.53–1.13, P=0.18), nor ARBs (HR, 0.88, 0.61–1.26, P=0.48), were associated with hospitalization risk. ACE inhibitors were associated with lower hospitalization risk in the older Medicare group (HR, 0.61, 0.41–0.93, P=0.02), but not the younger commercially insured group (HR, 2.14, 0.82–5.60, P=0.12; P‐interaction 0.09). Neither ACE inhibitors nor ARBs were associated with lower hospitalization risk in either population in the validation cohort. In the primary inpatient study cohort, neither ACE inhibitors (0.97, 0.81–1.16; P=0.74) nor ARBs (1.15, 0.95–1.38, P=0.15) were associated with in‐hospital mortality. These observations were consistent in the validation cohort. Conclusions ACE inhibitors and ARBs were not associated with COVID‐19 hospitalization or mortality. Despite early evidence for a potential association between ACE inhibitors and severe COVID‐19 prevention in older individuals, the inconsistency of this observation in recent data argues against a role for prophylaxis.

scholarly journals Impact of angiotensin receptor blocker product recalls on antihypertensive prescribing in Germany

2020 ◽  
Author(s):  
Ulrike Maria Rudolph ◽  
Salka Enners ◽  
Marita Kieble ◽  
Felix Mahfoud ◽  
Michael Böhm ◽  
...  
Keyword(s):  
Antihypertensive Drugs ◽  
Beta Blockers ◽  
Angiotensin Receptor Blockers ◽  
Fourth Quarter ◽  
Fixed Dose ◽  
Channel Blockers ◽  
Product Recalls ◽  
Angiotensin Receptor ◽  
Defined Daily Doses ◽  
The Impact

Abstract In Germany, ~8 million patients take angiotensin receptor blockers (ARBs) and 2.25 million of them valsartan. In 2018, contamination of generic ARBs with probable carcinogenic nitrosamines resulted in more than 30 recalls. The impact of such a huge recall has never been explored in Europe. We analyzed the utilization of valsartan, all ARBs, and other alternative antihypertensive drugs in Germany. We used our database of anonymized dispensing data from >80% of community pharmacies at the expense of the statutory health insurance (SHI) funds from January 2017 to December 2019. We analyzed 290.8 million prescriptions, including all oral mono- and fixed-dose combinations of ARBs and plausible alternatives, i.e. ACE inhibitors (ACEi), beta-blockers (BB), and calcium channel blockers (CCB). Utilization was calculated by defined daily doses per 1000 SHI-insured persons per day (DID). Valsartan use decreased substantially after the recalls in July 2018 from 39.0 to 14.2 DID (−64%) in the second quarter of 2019 and to 16.9 DID (−57%) in the fourth quarter of 2019. Simultaneously, the use of alternative ARBs increased from 77.7 DID in the second quarter of 2018 to 121.9 DID (+57%) in the fourth quarter of 2019, mainly due to an increase of candesartan dispensing to 99.8 DID (+73%). There were no changes in the utilization of ACEi, BB, or CCB. The majority of recalled generic valsartan products were replaced by other ARBs, predominantly candesartan, despite documented drug shortages. In contrast to previous safety warnings/recalls, our data do not suggest an under-prescription of antihypertensives during this period.

Angiotensin converting enzyme inhibitor and angiotensin receptor blocker use and outcomes in patients with colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 544-544 ◽  
Author(s):  
Sherilyn Alvaran Tuazon ◽  
Gentry Teng King ◽  
Joanna Paula Pingol Sta. Cruz ◽  
Jean B. Ong Kian Koc ◽  
Young Kwang Chae ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Disease Free Survival ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

544 Background: Increasing evidence implicates angiotensin in the pathophysiology of carcinogenesis. Both Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) have shown in-vitro activity in Colorectal Cancer (CRC) via inhibition of both VEGF and IGF-1 and present a novel therapeutic strategy. This study aimed to investigate the association of these agents in outcomes of patients with CRC. Methods: We reviewed the medical records of patients with stage I-III CRC from 2004-2008. ACEI and ARB use was defined as consumption for at least 3 months in patients with no evidence of disease after initial diagnosis and treatment. Outcomes were Disease Free Survival (DFS) and Overall Survival (OS). Kaplan-Meier and Cox proportional hazards regression were used. Results: A total of 222 patients were included, with a median follow up of 39 months. A total of 105 (47%) were identified as users of ACEI/ARBs. Multivariate analysis, adjusted to age, sex, race, stage, grade, tumor location, adjuvant chemotherapy, radiotherapy, statin and ASA use showed significantly improved DFS among users of ACEI and/or ARBs compared to non-users (HR = 0.44, p = 0.003). Considered separately, users of ACEIs only and users of ARBs only had better DFS than non-users (HR = 0.43 and 0.53, respectively). Compared directly, users of ACEIs did not have significantly different DFS than users of ARBs (HR = 0.81, p = 0.678). With regards to OS, multivariate analysis showed that, compared to non-users, patients with ACEI or ARB use had better OS, although non-significantly (HR = 0.59, p = 0.219). However, the magnitude of the impact on OS was comparable to that seen for DFS. Conclusions: The use of ACEIs and/or ARBs is associated with improved disease-free survival in CRC patients. There was a statistically insignificant trend toward improved OS, which may be related to the low power to the study. This observation warrants further exploration.

scholarly journals Angiotensin Receptor Antagonists to Prevent Sudden Death in Heart Failure: Does the Dose Matter?

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Pietro Francia ◽  
Francesca Palano ◽  
Giuliano Tocci ◽  
Carmen Adduci ◽  
Agnese Ricotta ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Beta Blockers ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Pharmacological Therapy ◽  
Angiotensin Receptor ◽  
Icd Implantation ◽  
Severe Left Ventricular Dysfunction ◽  
The Impact

International guidelines recommend ICD implantation in patients with severe left ventricular dysfunction of any origin only after careful optimization of medical therapy. Indeed, major randomized clinical trials suggest that suboptimal use of fundamental drugs, such as ACE inhibitors (ACE-i) and beta-blockers, may affect ICD shock-free survival, sudden cardiac death (SCD), and overall mortality. While solid evidence in favour of pharmacological therapy based on ACE-i with or without beta-blockers is available, data on SCD in HF patients treated with angiotensin receptor blockers (ARBs) are limited. The present paper systematically analyses the impact of ARBs on SCD in HF and reviews the contributory role of the renin-angiotensin system (RAS) to the establishment of arrhythmic substrates. The following hypothesis is supported: (1) the RAS is a critical component of the electrical remodelling of the failing myocardium, (2) RAS blockade reduces the risk of SCD, and (3) ARBs represent a powerful tool to improve overall survival and possibly reduce the risk of SCD provided that high doses are employed to achieve optimal AT1-receptor blockade.

scholarly journals Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARB) Are Protective Against ICU Admission and Mortality for Patients With COVID-19 Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Rawan ElAbd ◽  
Dana AlTarrah ◽  
Sarah AlYouha ◽  
Hamad Bastaki ◽  
Sulaiman Almazeedi ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Disease Severity ◽  
Angiotensin Receptor Blockers ◽  
Current Evidence ◽  
Secondary Outcome ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Icu Admission ◽  
Receptor Blockers ◽  
The Impact

Introduction: Corona Virus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. The aim of this study was to investigate the impact of being on an Angiotensin-Converting Enzyme Inhibitors (ACEI) and/or Angiotensin Receptor Blockers (ARB) on hospital admission, on the following COVID-19 outcomes: disease severity, ICU admission, and mortality.Methods: The charts of all patients consecutively diagnosed with COVID-19 from the 24th of February to the 16th of June of the year 2020 in Jaber Al-Ahmed Al-Sabah hospital in Kuwait were checked. All related patient information and clinical data was retrieved from the hospitals electronic medical record system. The primary outcome was COVID-19 disease severity defined as the need for Intensive Care Unit (ICU) admission. Secondary outcome was mortality.Results: A total of 4,019 COVID-19 patients were included, of which 325 patients (8.1%) used ACEI/ARB, users of ACEI/ARB were found to be significantly older (54.4 vs. 40.5 years). ACEI/ARB users were found to have more co-morbidities; diabetes (45.8 vs. 14.8%) and hypertension (92.9 vs. 13.0%). ACEI/ARB use was found to be significantly associated with greater risk of ICU admission in the unadjusted analysis [OR, 1.51 (95% CI: 1.04–2.19), p = 0.028]. After adjustment for age, gender, nationality, coronary artery disease, diabetes and hypertension, ICU admission was found to be inversely associated with ACEI use [OR, 0.57 (95% CI: 0.34–0.88), p = 0.01] and inversely associated with mortality [OR, 0.56 (95% CI: 0.33–0.95), p = 0.032].Conclusion: The current evidence in the literature supports continuation of ACEI/ARB medications for patients with co-morbidities that acquire COVID-19 infection. Although, the protective effects of such medications on COVID-19 disease severity and mortality remain unclear, the findings of the present study support the use of ACEI/ARB medication.

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