Effects Of Angiotensin II Receptor Blockers Research Articles

Rationale and Design of a Randomized, Open-Label, Parallel-Group Study of Esaxerenone Versus Angiotensin Receptor Blockers in Older Patients With Uncontrolled Hypertension on Calcium Channel Blocker Monotherapy (ESCORT-HT).

Angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) are commonly prescribed as first- and second-line treatments for older Japanese patients with hypertension. However, due to age-related decline in renin activity, the effectiveness of ARBs may decrease. This highlights the need for other antihypertensive agents to be used in combination with CCBs to replace ARBs for more effective blood pressure (BP) control. The ESCORT-HT study is a multicenter, randomized, controlled, open-label, parallel-group study with a 4-week run-in period and 12-week treatment period. This study aims to evaluate the efficacy of esaxerenone as a second-line treatment for hypertension and to determine whether its BP-lowering effect is noninferior to that of ARBs in older patients with uncontrolled hypertension on CCB monotherapy. The safety profiles of esaxerenone and ARBs will also be evaluated. Patients will be randomly assigned in a 1:1 ratio to receive either esaxerenone or an ARB. The primary efficacy endpoint will be the change from baseline in morning home systolic BP at the end of the treatment period. The BP-lowering effect of esaxerenone will be considered noninferior to that of ARBs if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic BP change between esaxerenone and ARB is <3.8mmHg, and will be considered superior if the upper limit of the two-sided 95% CI is <0. The findings may elucidate the possible benefits of earlier use of mineralocorticoid receptor blockers in combination with CCBs in older patients with essential hypertension.

Impact of Angiotensin Receptor Blockers (ARB) versus Other Antihypertensive Medication on Blood Pressure in Patients on Dialysis: A Meta-Analysis.

Hypertension is an important factor driving mortality among dialysis patients. Angiotensin-II receptor blocker (ARB) has been effective similarly to angiotensin-converting enzymes (ACEs) but with a low incidence of side effects. The meta-analysis included all published studies that investigated the effect of ARB on the hypertension in adult dialysis patients (≥18 years). Data extraction was guided by a predetermined checklist. Data sources of the retrieved studies were PubMed, MEDLINE, ScienceDirect, SCOPUS, Cochrane, Web of knowledge, and Google Scholar were systematically searched until February 2023. Using the RevMan 5 software, the mean difference for systolic and diastolic BP (SBP and DBP) and the risk ratio (RR) of the adverse events (AEs) were pooled from the selected studies. The random-effects model was used to compare the difference in the pre-and post-dialysis of the SBP and DBP. Data analyses were performed from December 2022 to February 2023. The primary outcome was the reduction in SBP and DBP in dialysis hypertensive patients who were on anti-hypertensive agents, and the secondary outcome was assessment of AE associated with the drug after dialysis (PROSPERO Registration: CRD42022355369). The initial search yielded 1,679 records, of which 84 studies underwent full-text evaluation, which identified 13 studies and 1,462 patients. The pooled standard MD for losartan with other anti-hypertensive agents, where the pre-dialysis SBP was 0.17 (95% confidence interval [CI]: -0.21-0.55) and the post-dialysis was 0.35 (95% CI: -0.17-1.02); yet, both are statistically non-significant, implies that there was no difference between Losartan and ARB drugs regarding the effect on the SBP. Diastolic BP for predialysis was -0.01 (95% CI: -0.65-0.63) and post-dialysis was 0.03 (95% CI: -0.24-0.30) and statistically non-significant. AEs by the ARB agents were lower compared to other anti-antihypertensive agents (relative risk [RR]: 1.01; 95% CI: 0.59-1.75) and statistically non-significant. This systematic review and meta-analysis of RCT demonstrated that ARB and other anti-hypertensive medications had similar impacts on the treatment of hypertension.

The Potential Impact of Renin-Angiotensin System Inhibitors on Cancer Survival and Recurrence: A Systemic Review and Meta-Analysis.

Renin-angiotensin system inhibitors (RASis), specifically angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs), are widely used antihypertensives. Their impact on the prognostic outcomes among patients with cancer has been subject to scrutiny and debate. The aim of this study was to evaluate the effect of RASis on survival in patients with cancer.We systematically searched PubMed, Web of Science, Embase, and Cochrane Library for relevant studies published until April 1, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEis on cancer prognosis compared with a control group and reported the survival outcomes and hazard ratios were included in the analysis. From each study, pooled hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity.61 studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASis improved overall survival (HR = 0.88; 95% CI, 0.82-0.93; P < 0.0001), progression-free survival (HR = 0.72; 95% CI, 0.65-0.79; P < 0.00001), disease-specific survival (HR = 0.86; 95% CI, 0.71-1.04; P = 0.03), and recurrence-free survival (HR = 0.74; 95% CI, 0.58-0.93; P = 0.01) in patients with cancer. The effect of RASis on overall survival varied depending on the type of cancer or type of RASis (ACEis or ARBs), according to subgroup analysis.The usage of renin-angiotensin system inhibitors has a positive impact on survival outcomes and recurrence among patients with cancer.

Efficacy and safety of losartan in childhood immunoglobulin A nephropathy: a prospective multicenter study

Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria.Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks.Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period.Conclusions: Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. &lt;i&gt;ClinicalTrials.gov trial registration (NCT0223277)&lt;/i&gt;

Angiotensin II Receptor Blockers Cause Changes in Prostate-specific Antigen Levels: A Retrospective Cohort Study.

We previously reported a decrease in prostate-specific antigen (PSA) levels in patients with castration-resistant prostate cancer treated with angiotensin II receptor blockers (ARBs). However, no studies have reported the effect of ARBs on PSA variability in patients without a history of prostate cancer. Therefore, we conducted a population-based, retrospective study to determine whether ARBs have an inhibitory effect on elevated PSA levels in Japanese patients without a history of prostate cancer. This study was conducted using a large-scale Japanese claim database, including male patients aged ≥60 years who had two or more PSA measurements with an interval between measurements of 3 months to 2 years between April 2008 and June 2019. Patients who had been prescribed ARBs were grouped into the ARB group, and those who were prescribed antihypertensive drugs other than ARBs were grouped into the non-ARB group. We compared the proportions of patients with second PSA levels greater than the first. The numbers of eligible patients in the ARB and non-ARB groups were 777 and 527, respectively. Multivariate logistic regression analysis revealed that the proportion of patients with elevated PSA levels was significantly lower in the ARB group than in the non-ARB group (adjusted odds ratio=0.80, 95% confidence interval=0.64-0.99, p=0.047). ARBs may suppress elevated PSA levels in patients without a history of prostate cancer. This contributes to the prevention of prostate cancer.

Therapeutic effects of candesartan in inflammatory skin disorders by suppressing Th17 differentiation

As angiotensin II is associated with inflammation, type I angiotensin II receptor blockers (ARBs) exibit anti-inflammatory effects in patients with hypertension as well as inflammatory disease animal models including arthritis models. The present study aimed to investigate whether ARBs exert anti-inflammatory effects in vivo in skin disorders. We tested effects of ARBs on 1-chloro-2,4-dinitrobenzene(CDNB)-induced atopic dermatitis-like and imiquimod-induced psoriasis-like skin models. CDNB-induced atopic dermatitis-like skin lesions were suppressed by administration of candesartan or telmisartan. The suppressive effect of telmisartan was blocked by the presence of GW9662, a selective PPARγ inhibitor, but not that of candesartan. Both ARBs suppressed increases in pro-inflammatory cytokine (IL-4, IL-13, IFN-γ, and IL-17A) levels, and GW9662 inhibited telmisartan-induced suppression but not candesartan. Candesartan significantly inhibited in vitro differentiation of naïve T cells into Th17 cells to a greater extent than telmisartan. In the imiquimod-induced psoriasis model, whose primary etiology is activation of IL-23/IL-17 axis, candesartan significantly suppressed psoriasis-like skin lesions and Th17 cell populations in both lymph nodes and spleens to a greater extent than telmisartan. Overall, certain ARBs may have anti-inflammatory effects in skin diseases. Candesartan may have therapeutic implications in inflammatory skin disorders by suppressing Th17 differentiation, while telmisartan might have therapeutic potential by activating PPARγ.

The association between angiotensin receptor blockers and lung, bladder, and colon cancer development: A 10-year multicentric retrospective Lebanese study.

Cardiovascular diseases (CVD) are the leading cause of death globally, followed by cancer. Angiotensin II contributes greatly to CVD pathogenesis, and Angiotensin II receptor blockers (ARBs) constitute a mainstay in hypertension and CVD management. However, the relationship between ARBs and cancer initiation is controversial, with no clear data in Lebanon. Therefore, our study aimed to determine the association between ARBs intake and lung, bladder, and colorectal cancers development in the Lebanese population. A retrospective study was conducted on 709 subjects divided into 2 main groups: Control (subjects without cancer; n = 177), and Cases (patients with cancer (n = 532): lung, bladder, or colorectal), taking ARBs (n = 236, (n = 121 in control and n = 115 in cases)) or not (n = 473). Collected information included the patients demographics, comorbidities, cancer's risk factors, and ARBs dose and duration intake. Bivariate, multivariate, and binary logistic analyses were enrolled. ARBs use was significantly protective (P value = 0.000) against overall cancer development (odds ratio [OR] = 0.127) and against each, lung (OR < 1), bladder (OR < 1), and colorectal cancers (OR < 1). A duration-response relationship was established. This protective effect and the time-dependent relationship remained unchanged after omitting the most relevant risk factors. In summary, a significant overall protective effect of ARBs against lung, bladder and colorectal cancers was found. This beneficial response was time-dependent. These results can guide patients on treatment options and clinicians for informed decision-making.

Prophylactic effect of angiotensin receptor blockers in children with genetic aortopathies: the early bird catches the worm

AimsIn genetic aortopathies (GA) particular attention is paid to aortic root dilatation which has an impact on morbidity and mortality. This study focuses on the effects of therapy with angiotensin-II-receptor-blockers (ARB) or beta-blockers (BB) on aortic root growth and the question which therapy should be initiated at which dosage and at what age.MethodsSince 1998 we diagnosed 208 patients with GA (170 FBN-1). 81 patients between 5 months and 18 years receiving either ARB or BB therapy were included. We retrospectively analyzed the progression of the dilatation of Sinus Valsalva aortae (SV) using calculated z-scores before and after therapy initiation and compared BB and ARB treatment.ResultsBoth ARB and BB (p < 0.05) therapy showed significant improvement in aortic root growth, while the effect is significantly more pronounced in ARB (p < 0.01) independent of age and genetic cause. A detailed comparison of the two drug groups showed a more sustained effect in limiting the progression of the dilatation of the aortic root in patients treated with ARB. Progression of dilatation of the SV was significantly lower in children treated with ARBs compared to BB (delta z-score, p < 0.05). In addition, ARBs were better tolerated and had a significantly lower discontinuation rate (3%) compared to BB (50%) (p < 0.01). Independently of age at initiation all children and adolescents were able to reach the target dose under ARB.ConclusionWe demonstrated a significant change in both treatment options, with the effect of ARB being more pronounced while being better tolerated throughout the treatment period.

RAAS ANTAGONISTS IN THE TREATMENT OF ARTERIAL HYPERTENSION IN PATIENTS WITH COVID-19-ASSOCIATED PNEUMONIA

Coronavirus disease COVID-19 has become a pandemic of the 21st century. According to the WHO data, more than 6.2 million people have died worldwide. Arterial hypertension (AH) is a risk factor for a severe course of COVID-19. AH doubles the risk of a lethal outcome twice. Therefore, the determination of the antihypertensive drug effect on the clinical course of coronavirus disease COVID-19 complicated by pneumonia is actual.&#x0D; Aim. The research is aimed to determine the effect of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs) on the course of coronavirus disease COVID-19 complicated by pneumonia in unvaccinated patients with AH.&#x0D; Materials and methods. 77 unvaccinated patients hospitalized for coronavirus disease COVID-19 complicated by pneumonia were enrolled in the research. The patients included in the research were divided into 3 groups: the first group included 41 patients treated with ACE inhibitors, the second group included 22 patients who received ARBs, and the control group included 14 patients who took neither ACEi nor ARBs. None of the patients received statins.&#x0D; Results. The mean age in the three groups did not differ statistically (69.0 ± 2.6 years in the first group, 68.0 ± 2.9 years in the second group and 69.0 ± 6.4 years in the control group, p = 0.91). There was not statistical difference in body mass index in patients of all three groups (28.0 ± 1.6 kg/m2 in the first group, 29.3 ± 2.4 kg/m2 in the second and 28.1 ± 2.8 kg/m2 in the control group, p = 0.67). 5 (12.2%) patients in the first group, 4 (18.2%) patients in the second group and 2 (14.3%) patients in the third group died (p = 0.81). Oxygen therapy was used in 16 (39.0%) patients of the first group and in 14 (63.6%) patients of the second group (p = 0.07). During the hospital stay, a decline in the oxygen saturation &lt;92% was observed in 17 (41.5%) patients of the first group, 12 (54.5%) in patients of the second group and 5 (35.7%) patients of the third group (p = 0.48). There was no significant difference in the number of patients treated with continuous positive airway pressure in all three groups (p=0.83), as well as invasive mechanical ventilation (p = 0.91). In the first and second groups, shortness of breath at the time of discharge was observed less frequently compared with the control group (p = 0.03). The number of points on the CAP-Sym questionnaire at the time of hospitalization was 25.8 ± 3.3 points in the first group, 29.5 ± 5.6 points in the second group and 26.5 ± 7.2 points in the control group (p = 0.51). At the time of discharge, the number of points on the CAP-Sym questionnaire in patients of the first group was 14.0 ± 2.5 points, in patients of the second group - 18.2 ± 3.7 points, in patients of the control group - 17.3 ± 4.4 points (p = 0.14).&#x0D; Conclusions. There was no effect of ACEi and ARBs on the severity and mortality of pneumonia associated with coronavirus disease COVID-19, compared with other antihypertensive drugs. Patients receiving ACE inhibitors tended to require supplemental oxygen less frequently than patients receiving ARBs. Patients taking ACE inhibitors or ARBs were less likely to complain of shortness of breath at the time of discharge than patients with hypertension whose antihypertensive therapy included neither ACE inhibitors nor ARBs.

The clinical and bioinformatics analysis for the role of antihypertension drugs on mortality among patients with hypertension hospitalized with COVID-19.

Comorbidities such as hypertension could exacerbate symptoms of coronaviral disease 2019 (COVID)‐19 infection. Patients with hypertension may receive both anti‐COVID‐19 and antihypertension therapies when infected with COVID‐19. However, it is not clear how different classes of anti‐hypertension drugs impact the outcome of COVID‐19 treatment. Herein, we explore the association between the inpatient use of different classes of anti‐hypertension drugs and mortality among patients with hypertension hospitalized with COVID‐19. We totally collected data from 278 patients with hypertension diagnosed with COVID‐19 admitted to hospitals in Wuhan from February 1 to April 1, 2020. A retrospective study was conducted and single‐cell RNA‐sequencing (RNA‐Seq) analysis of treatment‐related genes was performed. The results showed that Angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) drugs significantly increased the survival rate but the use of angiotensin‐converting enzyme inhibitor/β‐block/diuretic drugs did not affect the mortality caused by COVID‐19. Based on the analysis of four public data sets of single‐cell RNA‐Seq on COVID‐19 patients, we concluded that JUN, LST1 genes may play a role in the effect of ARB on COVID‐19‐related mortality, whereas CALM1 gene may contribute to the effect of CCB on COVID‐19‐related mortality. Our results provide guidance on the selection of antihypertension drugs for hypertensive patients infected with COVID‐19.

An umbrella review and meta-analysis of the use of renin-angiotensin system drugs and COVID-19 outcomes: what do we know so far?

IntroductionCoronavirus disease 2019 (COVID-19) is caused by the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), and commonly presents with fever, loss of smell/taste, and a persistent cough; in severe cases, patients require hospitalisation and external ventilation. Advanced age and pre-existing conditions such as cardiovascular diseases and diabetes have been associated with an increased risk of COVID-19 related mortality.Based on their mechanisms of action and widespread use among patients at high risk of poor disease outcomes, the impact of renin-angiotensin-aldosterone system (RAAS) inhibitors – including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) – on COVID-19 related outcomes has become a topic of interest, resulting in rapid dissemination of a large number of predominantly retrospective, observational studies since early 2020. Since many of these studies were limited in scope and results were inconclusive, systematic reviews and meta-analyses of published and unpublished findings swiftly followed.AimTo assess the effect of ACEIs and ARBs on COVID-19 related outcomes by summarising the currently available evidence.MethodsUmbrella review of systematic reviews and subsequent meta-analysis. Eligible for inclusion were systematic reviews with meta-analysis focusing on patients with or without COVID-19 exposed to ACEIs and/or ARBs compared to patients not exposed to the medication. Outcomes of interest included risk of infection; hospitalisation; severity; and death. Reviews were identified through a literature search in Medline, EMBASE, Scopus, the Cochrane database of systematic reviews, and medRxiv, from 2019 until 1st of February 2021. Data was extracted using a standardised extraction sheet; the AMSTAR 2 Critical Appraisal Tool for systematic reviews was used for quality assessment. Heterogeneity between studies was evaluated using I2 statistics, and findings of included meta-analyses were summarised using random-effects models. The protocol was registered with PROSPERO (CRD42021233398).ResultsOut of an initial 157 publications, 66 systematic reviews underwent full text screening; after further exclusions based on pre-specified criteria, 47 studies were identified to be relevant. The number of included studies as well as the outcomes of interest varied widely between reviews, with death being the most common.Odds ratio for risk of COVID-19 infection among patients treated with ACEIs/ARBs versus patients not on treatment was 0.99 (95% Confidence Interval (CI) 0.97 – 1.02; 19 studies, I2 = 24.7%); and for hospitalisation among COVID-19 patients treated with ACEIs/ARBs versus not on treatment, 1.23 (95% CI 1.04 – 1.46; 11 studies, I2 = 76.4%); severe disease 0.86 (95% CI 0.78 – 0.95; 28 studies, I2 = 68%); and death, 0.80 (95% CI 0.75 – 0.86; 47 studies, I2 = 51.9%).ConclusionWhile treatment with ACEIs or ARBs does not appear to impact the risk of COVID-19 infection, it appears that patients on treatment have lower risks of severe disease and mortality compared to patients not on ACEIs/ARBS treatment. Findings should be interpreted cautiously as the systematic reviews/meta-analyses included in this study were of variable quality, and there was high heterogeneity among studies for most outcomes. Findings will inform evidenced-based guidelines on the appropriate measures for patients at risk of COVID-19 infection and prescribed RAAS inhibitors.

The use of angiotensin II receptor blocker is associated with greater recovery of cardiac function than angiotensin-converting enzyme inhibitor in dilated cardiomyopathy.

AimsAngiotensin‐converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) have been shown to be associated with recovery of cardiac function in patients with dilated cardiomyopathy (DCM). The aim of this study was to assess comparative effectiveness of ACEis vs. ARBs on recovery of left ventricular ejection fraction (LVEF) among patients with DCM.Methods and resultsWe analysed the clinical personal records of DCM, a national database of the Japanese Ministry of Health, Labour and Welfare, from 2003 to 2014. Patients with LVEF < 40% and on either ACEis or ARBs were included. Eligible patients were divided into two groups according to the use of ACEis or ARBs. A one‐to‐one propensity case‐matched analysis was used. The primary outcome was defined as LVEF ≥ 40% at 3 years of follow‐up. Out of 4618 eligible patients, 2238 patients received ACEis and 2380 patients received ARBs. Propensity score matching yielded 1341 pairs. Mean age was 56.0 years, 2041 (76.1%) were male, median duration of heart failure was 1 year, and mean LVEF was 27.6%. The primary outcome was observed more frequently in ARB group than in ACEi group (59.8% vs. 54.1%; odds ratio 1.26; 95% confidence interval 1.08–1.47; P = 0.003). The per‐protocol analysis showed similar results (62.0% vs. 54.0%; odds ratio 1.39; 95% confidence interval 1.17–1.66; P < 0.001). The change in LVEF from baseline to 3 years of follow‐up was greater in ARB group than in ACEi group (15.8 ± 0.4% vs. 14.0 ± 0.4%, P = 0.003). The subgroup analysis showed that this effect was observed independently of systolic blood pressure, heart rate, LVEF, chronic kidney disease, and concomitant use of beta‐blockers and mineralocorticoid receptor antagonists.ConclusionsThe use of ARBs was associated with LVEF recovery more frequently than ACEis among patients with DCM and reduced LVEF.

Angiotensin blockade therapy and survival in pancreatic cancer: a population study

BackgroundPancreatic cancer (PC) is one of the most aggressive and challenging cancer types to effectively treat, ranking as the fourth-leading cause of cancer death in the United States. We investigated if exposures to angiotensin II receptor blockers (ARBs) or angiotensin I converting enzyme (ACE) inhibitors after PC diagnosis are associated with survival.MethodsPC patients were identified by ICD-9 diagnosis and procedure codes among the 3.7 million adults living in the Emilia-Romagna Region from their administrative health care database containing patient data on demographics, hospital discharges, all-cause mortality, and outpatient pharmacy prescriptions. Cox modeling estimated covariate-adjusted mortality hazard ratios for time-dependent ARB and ACE inhibitor exposures after PC diagnosis.Results8,158 incident PC patients were identified between 2003 and 2011, among whom 20% had pancreas resection surgery, 36% were diagnosed with metastatic disease, and 7,027 (86%) died by December 2012. Compared to otherwise similar patients, those exposed to ARBs after PC diagnosis experienced 20% lower mortality risk (HR=0.80; 95% CI: 0.72, 0.89). Those exposed to ACE inhibitors during the first three years of survival after PC diagnosis experienced 13% lower mortality risk (HR=0.87; 95% CI: 0.80, 0.94) which attenuated after surviving three years (HR=1.14; 95% CI: 0.90, 1.45).ConclusionsThe results of this large population study suggest that exposures to ARBs and ACE inhibitors after PC diagnosis are significantly associated with improved survival. ARBs and ACE inhibitors could be important considerations for treating PC patients, particularly those with the worst prognosis and most limited treatment options. Considering that these common FDA approved drugs are inexpensive to payers and present minimal increased risk of adverse events to patients, there is an urgent need for randomized clinical trials, large simple randomized trials, or pragmatic clinical trials to formally and broadly evaluate the effects of ARBs and ACE inhibitors on survival in PC patients.

Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease.

Radiation-induced heart disease (RIHD) is a potential late side-effect of thoracic radiotherapy resulting in left ventricular hypertrophy (LVH) and fibrosis due to a complex pathomechanism leading to heart failure. Angiotensin-II receptor blockers (ARBs), including losartan, are frequently used to control heart failure of various etiologies. Preclinical evidence is lacking on the anti-remodeling effects of ARBs in RIHD, while the results of clinical studies are controversial. We aimed at investigating the effects of losartan in a rat model of RIHD. Male Sprague-Dawley rats were studied in three groups: (1) control, (2) radiotherapy (RT) only, (3) RT treated with losartan (per os 10 mg/kg/day), and were followed for 1, 3, or 15 weeks. At 15 weeks post-irradiation, losartan alleviated the echocardiographic and histological signs of LVH and fibrosis and reduced the overexpression of chymase, connective tissue growth factor, and transforming growth factor-beta in the myocardium measured by qPCR; likewise, the level of the SMAD2/3 protein determined by Western blot decreased. In both RT groups, the pro-survival phospho-AKT/AKT and the phospho-ERK1,2/ERK1,2 ratios were increased at week 15. The antiremodeling effects of losartan seem to be associated with the repression of chymase and several elements of the TGF-β/SMAD signaling pathway in our RIHD model.

Angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers: New-onset diabetes mellitus stratified by statin use.

Regardless of statin use, which is known to induce hyperglycaemia, comparative studies on the risk of new-onset diabetes mellitus (NODM) with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are needed. This study evaluated the effects of ACEIs and ARBs on NODM in the clinical setting. This retrospective cohort study utilized electronic medical record data from Seoul St. Mary's Hospital and Seoul National University Hospital from 2009 to 2012. Patients who were prescribed ACEIs or ARBs for the first time (irrespective of concomitant statin use) were followed up for 5years. A total of 11,703 patients were included, 24.9% (n=2916) were taking ACEIs and 75.1% (n=9189) were taking ARBs. Patients on ACEIs had a significantly lower incidence of NODM both with statin use (HR=0.13, p<0.001) and without (HR=0.15, p=0.009) than patients on ARBs. Age ≥60years (HR=1.49, p=0.010), BMI ≥25 (HR=1.96, p<0.010), use of calcium channel blockers (HR=1.47, p=0.010), and diuretics (HR=1.48, p=0.010) were risk factors for NODM with statin use. Patients taking ACEIs are less likely to develop NODM than patients taking ARBs, irrespective of statin use. Patients' conditions, including the risk of NODM, should be considered before prescribing ACEIs or ARBs. Future randomized clinical trials are needed to clarify further the relationship between ACEIs and ARBs and their effect on NODM.

Effect of medical treatment on heart failure incidence in patients with a systemic right ventricle

To date, clinical trials have been underpowered to demonstrate a benefit from ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) in preventing systemic right ventricle (sRV) failure and disease progression in patients with transposition of the great arteries (TGA). This observational study aimed to estimate the effect of ACEi and ARB on heart failure (HF) incidence and mortality in a large population of patients with an sRV. Data on all patients with an sRV under active follow-up at two tertiary centres between January 2007 and September 2018 were studied. The effect of ACEi and ARB on the incidence of HF and mortality was estimated using a propensity score weighting approach to control confounding. Among the 359 patients with an sRV (32.2 (IQR 26.4–38.3) years, 59.3% male, 66% complete TGA with atrial switch repair and 34% congenitally corrected TGA), 79 (22%) had a moderate to severe sRV dysfunction and 138 (38%) were treated with ACEi or ARB. Fourteen (3.6%) patients died, 8 (2.1%) underwent heart transplantation and 46 (11.8%) had a new HF event over a median follow-up of 7.1 (IQR 4.0–9.4) years. On multivariate Cox analysis with adjustment using propensity score weighting approaches, ACEi or ARBs treatment was not significantly associated with a lower HF incidence or mortality in patients with an sRV. Despite significant neurohormonal activation described in patients with an sRV, there is still no evidence of a beneficial effect of ACEi or ARB on morbidity and mortality in this population.

Effect of Angiotensin Receptor Blocker and Angiotensin Converting Enzyme Inhibitor on Kidney Function and Blood Potassium Level in Indonesian Type 2 Diabetes Mellitus with Hypertension: A Three-Month Cohort Study.

PurposeNational formulary restrictions in Indonesia (2019) require estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 to be able to prescribe telmisartan and valsartan and ACE-I intolerance to be able to prescribe irbesartan and candesartan. These restrictions are based on economic considerations and differ from American Diabetes Association (ADA) (2020) guidelines which allow equal use of angiotensin II receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACE-I) without restriction. Since there is a need to evaluate the different effects of ACE-I and ARB in the Indonesian hypertensive type 2 diabetes mellitus (T2DM) population, we compare their effects on urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and blood potassium level.Patients and MethodsA prospective cohort study at RSUPN Dr. Cipto Mangunkusumo Hospital was conducted in 123 T2DM patients. We followed the study subjects prospectively for three months using a validated questionnaire, health record, and laboratory data.ResultsAfter 3 months of observation, there were no significant changes, except increased BMI values (p = 0.046) in the ACE-I group, and decreased LDL value (p = 0.016) and HDL value (p = 0.004) in the ARB group. Multivariate analysis showed that the consumption of ACE-I or ARB was not associated with a decrease/constant of UACR or increase potassium level, even after adjusting by confounding variables. Interestingly, we found ARB was more likely to increase eGFR, but the significance was lost once the duration of ACE-I/ARB use was entered into the model. In addition, BMI >25 kg/m2 was a significant factor associated with decreased/constant UACR, maleness was significant for increased eGFR, and declining systolic blood pressure for increase in potassium level.ConclusionACE-I and ARB have a similar effect on UACR and blood potassium level, but ARB slightly increased eGFR compared to ACE-I within three months of consumption.

Primary prevention of cardiovascular disease events with renin-angiotensin system blockade in autosomal dominant polycystic kidney disease dialysis patients: A nationwide cohort study.

Although renin-angiotensin system (RAS) blockade has been shown to reduce cardiovascular disease (CVD) in the general population and high-risk subjects, their protective effect in autosomal dominant polycystic kidney disease (ADPKD) patients under dialysis was still unknown. By using the database from 1995 to 2008 Taiwan National Health Insurance Research Database (Registry for Catastrophic Illnesses), we included 387 ADPKD patients who received dialysis therapy, aged ≥ 18 year-old, and with no evidence of CVD events in 1997 and 1998. We utilized Cox proportional hazards regression analysis and propensity score matching to evaluate adjusted hazard ratios for all-cause mortality and CVD events in users (n=231) and nonusers (n = 156) of an angiotensin-converting enzymes inhibitor (ACEI) / angiotensin II receptor blocker (ARB) during the 12 years of follow-up. All study subjects were followed up for more than 3 months. There was no significant difference between the ACEI/ARB treatment group and the control group in incident CVD events except ischemic stroke and transient ischemic accident (TIA). The results remain similar between groups before and after propensity score matching. Moreover, there was no significant difference in outcomes between ACEI/ARB treatment over 50% of follow-up period and without ACEI/ARB treatment after propensity score matching. This nationwide cohort study failed to prove the protective effects of long-term ACEI or ARB on incident CVD events among APKD dialysis patients. Further larger scale, multicenter and randomized control trials are warranted to show the causal association

Angiotensin II Receptor Blockers (ARBs Antihypertensive Agents) Increase Replication of SARS-CoV-2 in Vero E6 Cells.

Several comorbidities, including hypertension, have been associated with an increased risk of developing severe disease during SARS-CoV-2 infection. Angiotensin II receptor blockers (ARBs) are currently some of the most widely-used drugs to control blood pressure by acting on the angiotensin II type 1 receptor (AT1R). ARBs have been reported to trigger the modulation of the angiotensin I converting enzyme 2 (ACE2), the receptor used by the virus to penetrate susceptible cells, raising concern that such treatments may promote virus capture and increase their viral load in patients receiving ARBs therapy. In this in vitro study, we reviewed the effect of ARBs on ACE2 and AT1R expression and investigated whether treatment of permissive ACE2+/AT1R+ Vero E6 cells with ARBs alters SARS-CoV-2 replication in vitro in an angiotensin II-free system. After treating the cells with the ARBs, we observed an approximate 50% relative increase in SARS-CoV-2 production in infected Vero E6 cells that correlates with the ARBs-induced up-regulation of ACE2 expression. From this data, we believe that the use of ARBs in hypertensive patients infected by SARS-CoV-2 should be carefully evaluated.

Effect of medical treatment on heart failure incidence in patients with a systemic right ventricle

BackgroundTo date, clinical trials have been underpowered to demonstrate a benefit from ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) in preventing systemic right ventricle (sRV) failure and disease...