Angiotensin II Receptor Blockers Research Articles

The Autonomic Nervous System and Inflammation in Chronic Kidney Disease.

The autonomic nervous system plays a crucial role in regulating physiological processes and maintaining homeostasis through its two branches: the sympathetic nervous system (SNS) and the parasympathetic nervous system. Dysregulation of the autonomic system, characterized by increased sympathetic activity and reduced parasympathetic tone, is a common feature in chronic kidney disease (CKD) and cardiovascular disease. This imbalance contributes to a pro-inflammatory state, exacerbating disease progression and increasing the risk for cardiovascular events. The sympathetic system promotes inflammation by releasing catecholamines, which activate adrenergic receptors on immune cells. The parasympathetic system exerts anti-inflammatory effects via the cholinergic anti-inflammatory pathway mediated by the vagus nerve. Targeting the autonomic system to restore the balance between the sympathetic and the parasympathetic components offers promising approaches to reduce inflammation and improve outcomes in CKD and cardiovascular disease. Beta-blockers, angiotensin-converting enzyme inhibitors (ACEi), and angiotensin II receptor blockers (ARBs) are pharmacological agents that modulate sympathetic activity and have shown anti-inflammatory effects. Lifestyle interventions, such as a healthy diet, physical exercise, mindfulness, and meditation, enhance parasympathetic activity and improve autonomic function. Vagus nerve stimulation has emerged as a promising therapy, demonstrating significant potential in reducing inflammation and improving clinical outcomes in various conditions, including CKD, myocardial infarction and stroke. Despite mixed results in heart failure trials, vagal nerve stimulation has consistently improved quality-of-life measures. Understanding the mechanisms underlying autonomic system regulation of inflammation can inform the development of novel therapeutic strategies to restore autonomic balance and improve patient outcomes in CKD and cardiovascular disease.

Hypocapnia and its relationship with in-hospital mortality in acute heart failure patients: Insights from the Indonesian multicenter ICCU registry

Acute heart failure (AHF) presents serious risks for hospitalized patients. The aim of this study was to explore the relationship between arterial partial pressure of carbon dioxide (PaCO2) levels and outcomes in AHF patients admitted to the intensive cardiovascular care unit (ICCU), utilizing data from the IndONEsia ICCU Registry (One ICCU Registry). A multicenter retrospective observational study was performed covering data between August 2021-2023. Participants were categorized by PaCO2 levels: hypocapnia (<35 mmHg), normocapnia (35–45 mmHg), and hypercapnia (>45 mmHg). The primary outcomes included ICCU mortality, in-hospital mortality, and 30-day mortality, whereas the length of the stays in the ICCU or hospital and ventilation requirement were set as the secondary outcomes. Mortality risks were assessed using Cox proportional hazards models. Of the 1,870 patients, 1,102 (58.96%) had hypocapnia, 645 (34.5%) had normocapnia, and 123 (6.5%) had hypercapnia. Hypocapnia patients had significantly higher ICCU, in-hospital, and at 30-day mortality rates compared to normocapnic patients (all p<0.001), along with longer lengths of stay in ICCU and in hospital (p<0.001). Hypocapnia significantly increased noninvasive and mechanical ventilation requirement compared to normocapnia patients. Multivariate analysis identified factors impacting patients’ survival, including age, treatment with angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARBs) drugs, and severity scores such as the quick sequential organ failure assessment (qSOFA) and simplified acute physiology score II (SAPS II). In conclusion, hypocapnia in AHF patients could increase in-hospital, ICU and 30-days mortality rates and length of hospital stays, as well as noninvasive and mechanical ventilation requirements.

RNA-Seq transcriptomic landscape profiling of spontaneously hypertensive rats in youth treated with a ARNI versus ARB.

Angiotensin receptor-neprilysin inhibitor (ARNI) and angiotensin II receptor blockers (ARB) are antihypertension medications that improve cardiac remodeling and protect the heart. However, at the early stage of hypertension, it is still unclear how these two drugs affect the transcriptomic profile of multiple organs in hypertensive rats and the transcriptomic differences between them. We performed RNA sequencing to define the RNA expressing profiles of the eight tissues (atrium, ventricle, aorta, kidney, brain, lung, white fat, and brown fat) in spontaneously hypertensive rats (SHRs) and SHRs treated with ARNI or ARB. Acquired data was processed and analyzed by computational analyses (i.e., clustering, DEG, functional association, WGCNA, and protein-protein interaction (PPI) network analysis). We discovered that various tissues produced significant transcriptomic changes at the early stage of hypertension. The transcriptomic differences are notably in brown fat, kidney, lung, and brain tissues between ARNI and ARB treatment. Meanwhile, ARNI or ARB treatment can reverse the dysregulated expression genes related to the metabolism process, especially in brown fat, lung, and kidney tissues under hypertension. The current study has presented a comprehensive rat RNA-Seq transcriptomic landscape in SHRs and compared the transcriptome differences between ARNI and ARB treatment as a biomedical research resource for further study.

Insights from animal studies exploring the efficacy and safety of topical losartan, in prophylaxis and treatment of corneal scarring fibrosis.

Several studies in rabbits demonstrated the efficacy and safety of topical losartan, an angiotensin II receptor blockers (ARB) that modulates the TGF-β intracellular signaling pathways by inhibiting the activation of Extracellular Signal-regulated Kinase (ERK), in preventing or treating stromal fibrosis after a range of injuries such as Descemetorhexis, alkali burns, incisions, and photorefractive keratectomy (PRK). Several case reports have shown that topical losartan treatment is also efficacious and safe in humans to prevent or treat stromal fibrosis after many different injuries or diseases. Topical losartan penetrates the full thickness of the cornea and, therefore, can treat both anterior and posterior stromal fibrosis. These rabbit studies have demonstrated that there can be epithelial and stromal toxicity to losartan at dosages greater than 0.8 mg/ml and that higher dosages will not accelerate the return to transparency of fibrotic corneas. In corneas with an epithelial defect, it is likely safer to use 0.2 mg/ml losartan six times a day until the epithelium closes to further decrease the risk of epithelial toxicity before going to the 0.8 mg/ml six times a day dosage. Future clinical studies will explore additional questions, such as whether four times a day dosing is less effective than six times a day dosing in the treatment of stromal fibrosis.

Evaluation of Bone–Implant Interface: Effects of Angiotensin II Receptor Blockade in Hypertensive Rats

Hypertension is a global health concern not only correlated with cardiovascular complications, but also with impaired bone metabolism, potentially affecting healing at the bone–implant interface. Losartan, an angiotensin II receptor blocker (ARB) commonly prescribed for hypertension, has shown beneficial effects on bone healing in spontaneously hypertensive rats (SHRs). However, the influence of hypertension and ARBs like losartan on the bone cellular response at the bone–implant interface remains underexplored. Methods: A total of 32 rats were included in this study: 16 SHRs, with 8 receiving losartan (30 mg/kg daily) and 8 receiving no treatment, and 16 normotensive Wistar rats, with 8 receiving losartan and 8 receiving no treatment. After one week of treatment, titanium implants were placed into the tibia of all the animals. The bone–implant interface was assessed 60 days post-implantation using micro-computed tomography (µCT) and an immunohistochemical analysis. Results: (i) The ARB treatment significantly increased the bone volume and bone–implant contact in the SHRs receiving losartan compared to the untreated SHRs. (ii) Consistent with the µCT findings, the immunohistochemistry further confirmed regular bone turnover and increased osteocalcin (OC) mineralization in the treated SHRs. In contrast, no alterations in the bone microarchitecture were noted in the Wistar rats treated with losartan. Conclusions: The results suggest that losartan, an ARB drug, improves bone volume and bone turnover at the bone–implant interface in SHRs.

MR T2* Map to Predict Worsening Hypertension Control: A Preliminary Study.

Blood pressure measurement is important in monitoring hypertension. However, blood pressure does not provide much information about renal condition in treated hypertension. This study aimed to evaluate renal oxygenation in hypertensive patients using T2* mapping. Subgroup analysis explored whether R2* values can guide adjustments in antihypertensive treatment. A total of 140 consecutive subjects were recruited: 87 hypertensive subjects and 53 normotensive subjects. Hypertensive subjects were classified into non-medication (non-med), angiotensin II receptor blocker (ARB), and non-ARB-treated groups. Each group was divided into good and poor control subgroups based on blood pressure at enrollment. T2* mapping was utilized to assess renal cortical and medullary R2* values. After a 2-year follow-up, subjects were categorized into stable and unstable based on the need for treatment modifications. The unstable subgroup had higher medullary R2* values than the stable subgroup in all followed patients (p < 0.05). Additionally, the unstable merged non-med with ARB subgroup had higher medullary R2* values overall (p < 0.05) and within the good control subgroup (p < 0.05). Patients with stable hypertension, especially those with good control managed through lifestyle modifications or ARBs, exhibited lower renal medullary R2* values, suggesting higher renal oxygenation.

The efficacy and safety of Ginkgo biloba L. leaves extract combined with ACEI/ARB on diabetic kidney disease: a systematic review and meta-analysis of 41 randomized controlled trials.

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease in the world. However, the current conventional approaches have not yet achieved satisfactory efficacy. As one of the most influential products in botanical medicine, Ginkgo biloba L. leaves extract (GBE) demonstrates various pharmacological effects on DKD and is gradually used as an adjunctive therapy for this disease. A comprehensive analysis is necessary to evaluate the efficacy and safety of GBE as an adjuvant treatment for DKD. This meta-analysis aimed to evaluate the efficacy and safety of GBE as a supplementary treatment to conventional renin-angiotensin-aldosterone system inhibitors for DKD patients, providing a reference for subsequent research and clinical practice. This study has been registered in PROSPERO as CRD42023455792. Ten databases were searched from their inception to 21 July 2023. Randomized controlled trials about GBE and DKD were included. Review Manager 5.4 and Stata 16.0 were employed to conduct the analysis. Heterogeneity was assessed through the χ2 test and the I2 test, and the effect model was chosen accordingly. Meta-regression and subgroup analysis were performed to investigate the sources of heterogeneity and the influence of different factor levels on efficacy. The publication bias was evaluated with the funnel plot and Egger's test, and the evidence quality was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. A total of 41 studies with 3,269 patients were finally enrolled in this study. None of the included studies reported whether renal or cardiovascular disease progression events occurred. Compared with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) alone, the combination with GBE was more beneficial in improving urinary albumin excretion rate (UAER) [mean difference (MD) = -22.99μg/min, 95% confidence interval (CI): -27.66 to -18.31, p < 0.01], serum creatinine (SCr) [MD = -8.30μmol/L, 95% CI: -11.55 to -5.05, p < 0.01], blood urea nitrogen (BUN) [MD = -0.77mmol/L, 95% CI: -1.04 to -0.49, p < 0.01], 24-hour urinary total protein (24hUTP) [MD = -0.28g/d, 95% CI: -0.35 to -0.22, p < 0.01], cystatin C (Cys-C) [MD = -0.30mg/L, 95% CI: -0.43 to -0.17, p < 0.01], total cholesterol (TC) [MD = -0.69mmol/L, 95% CI: -1.01 to -0.38, p < 0.01], triglyceride (TG) [MD = -0.40mmol/L, 95% CI: -0.56 to -0.23, p < 0.01], low-density lipoprotein cholesterol (LDL-C) [MD = -0.97mmol/L, 95% CI: -1.28 to -0.65, p < 0.01], fasting blood glucose (FBG) [MD = -0.30mmol/L, 95% CI: -0.54 to -0.05, p = 0.02], hematocrit [MD = -4.58%, 95% CI: -5.25 to -3.90, p < 0.01] and fibrinogen [MD = -0.80g/L, 95% CI: -1.12 to -0.47, p < 0.01]. No significant improvement was found in 2-hour postprandial glucose (2hPG), glycated hemoglobin (HbA1c), diastolic blood pressure (DBP) and systolic blood pressure (SBP). No significant difference was detected in adverse events. Combining GBE with ACEI/ARB may improve UAER, SCr, BUN, 24hUTP, Cys-C, TC, TG, LDL-C, hematocrit and fibrinogen in DKD patients. It also seems beneficial for oxidative stress and inflammation but has minimal impact on glucose and blood pressure. Combined GBE therapy is generally tolerated, but safety monitoring remains essential during its use. More long-term high-quality clinical studies and in-depth molecular research are still necessary to provide stronger evidence regarding the benefits and safety of GBE in DKD. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=455792, identifier CRD42023455792.

Patients with Severe Obesity and Hypertension- Antihypertensive Treatment Before and After Bariatric Surgery-Five Years of Follow-Up

Background: Hypertension is the most common comorbidity associated with obesity. Hypertension can be treated with antihypertensive drugs, but weight loss can also lower BP, reducing the need for antihypertensive medication. Bariatric surgery is the most effective treatment for patients with severe obesity. Material and methods: The study group consisted of 30 obese patients with hypertension or newly diagnosed hypertension. Before laparoscopic sleeve gastrectomy (LSG) each patient was precisely interviewed, taking into account the antihypertensive drugs taken. We divided drugs into groups: betablockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), diuretics: thiazide diuretics / thiazide-like diuretics (TDs), loop diuretics (LDs), mineralocorticoid receptor antagonists (MRAs) and others: centrally acting drugs and alpha-blockers (ABs). Each patient had ABPM. Actually BMI and antihypertensive treatment was assessed 5 years after LSG. Results: The study group consisted of 30 patients with severe obesity (BMI≥40kg/m2) with an average age of 42.5 years (25-69), including 11 males and 19 females.17 of patients had been previously diagnosed and treated hypertension,13 had been newly diagnosed hypertension. The decrease in the frequency of ACEIs use before and after SLG was significant observed (from 83% to 24%,p&lt;0.001), CCBs (from 45% to 14%, p=0.008), TDs (from 31% to 3.5%, p=0.013).The decrease of body mass and BMI before and after SLG was significant(from 135kg to 100kg,p&lt;0.001; 47.3 to 33.8, p&lt;0.001). Antihypertensive medication was discontinued in a large proportion of patients after surgery, and the mean number of antihypertensive medications decreased. Bariatric procedures have strong evidence of efficacy and safety. Conclusions: Patients with severe obesity and hypertension should be offered surgical weight loss earlier in their disease process

Which Immunosuppressive Therapy should be used in Primary Membranous Glomerulonephritis?

Background: Different results have been reported on immunosuppressive treatments in patients with primary membranous nephropathy. In recent years, it has been determined that antiPLA2R antibodies can be used for the diagnosis of primary membranous glomerulonephritis. The aim of this study was to investigate the treatment responses of patients with primary membranous glomerulonephritis determined by the presence of PLA2-R antibody. Patients and Methods: Sixty patients (M:29, F:31) with membranous glomerulonephritis were retrospectively investigated. The presence of glomerular PLA2R antibodies were investigated by immunohistochemical method from the pathological specimen. Those patients were treated with immunosuppressants (methylprednisolon, cyclophosphamide, cyclosporine, azathioprine), and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB). The treatments were carried out with different combinations. The success of the treatment was defined as complete (&lt;0.3g/day), partial (&lt;3.5g/day or at least 50% reduction) or unresponsive (insufficient reduction) according to the reduction in proteinuria. In the patients, progression risks (low, moderate, high) were divided according to proteinuria and creatinine clearance. The results of immunosuppressive treatments were statistically analyzed, and p&lt;0.05 was accepted significant. Results Glomerular PLA2R antibodies were positive in 50 cases (87.7%), negative in 7 cases (12.2%). The mean duration of treatment of the patients was 23 months (6-58 months). With the treatment of PLA2R antibody-positive patients, 29% developed complete remission, 56% partial remission, and 15% did not respond. Complete remission was achieved only by steroid plus cyclophosphamide or cyclosporine combinations. The overall response (complete plus partial) rates were similar (respectively, 91% and 89%) in cyclophosphamide or cyclosporine treatment with steroids. The reduction rates in proteinuria were 70.6% in patients using cyclophosphamide, steroid, and ARB, and 79.5% in patients using cyclosporine, steroid, and ARB; there was no difference between them (P=0.67). In patients with positive PLA2R antibodies, the risk of progression was low in 25%, moderate in 29%, and high in 46%. When the treatment responses were examined, a lower rate of complete remission and higher partial remission were found in the high-risk group than in the low-risk group. However, overall response rates were not different in risk groups. Conclusion In primary membranous glomerulonephritis, only cyclophosphamide or combinations of cyclosporine and steroids provided complete remission. The complete plus partial response rates were similar in all risk groups.

Osteoporotic fracture risks of thiazides and dihydropyridines in angiotensin modulator users.

To determine whether thiazides, combined with either angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), offer bone-protective benefits compared with dihydropyridine (DHP) drugs combined with ACEi or ARB. This retrospective cohort study was conducted on the US Collaborative Network from the TriNetX database on March 5th, 2024. It included hypertensive ACEi or ARB users under thiazide or DHP drug treatments spanning from January 1st, 2015, to December 31st, 2022, with exclusion criteria applied. The primary outcome is a composite typical osteoporotic fracture (TOPF). Kaplan Meier analyses were performed after 1:1 propensity-score matching (PSM) with a 5-year follow-up. Besides investigating fracture-related outcomes in thiazide-ACEi/ARB and DHP-ACEi/ARB users, this study explores whether the effects differ between ACEi and ARB users. Subgroup analyses were also performed, and the heterogeneity among the results was assessed using Cochran's Q-tests. Post-PSM results yield 54,240 patients per cohort in the primary analysis, aging 61.5 ± 12.2 versus 61.4 ± 13.7 (thiazide-ACEi/ARB versus DHP-ACEi/ARB) with predominantly white ethnicity. Thiazide-ACEi/ARB users exhibit lower TOPF risk than DHP-ACEi/ARB users (hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.61-0.70), and such benefits from thiazides are similar between ACEi and ARB users (ACEi: HR = 0.69; ARB: HR = 0.67, Cochran's Q-test p-value = 0.78). Additionally, the effects of thiazides reveal significant heterogeneity between patients with and without inflammatory polyarthropathy (ICD-10, M05-M14) and benzodiazepine usage (Cochran's Q-test p-value = 0.01, 0.04). Thiazides are associated with lower risks of typical osteoporotic fractures compared to DHP drugs in patients treated with ACEi or ARB, while such benefits may diminish in those with a diagnosis of inflammatory polyarthropathy and benzodiazepine usage.

Impact of hyperkalaemia on renin–angiotensin–aldosterone (RAAS) inhibitor reduction or withdrawal following hospitalisation

BackgroundInhibitors of the renin–angiotensin–aldosterone system (RAAS), such as ACE inhibitors (ACEi), angiotensin-II receptor blockers and mineralocorticoid receptor antagonists, reduce morbidity and mortality in hypertension, congestive heart failure and chronic kidney disease. However, their use can lead to hyperkalaemia. We examined the proportions of RAAS inhibitor (RAASi) reduction or withdrawal, across GFR strata, following hospitalisation and the effect on patient mortality.MethodsThis was a retrospective cohort study of adult patients hospitalised from 1 January2017 to 31 December2020. Biochemistry data, clinical notes and medicines use were extracted using the CogStack platform, from electronic health records. Patients were identified by creatinine measurement during hospitalisation. Hyperkalaemia was defined as potassium > 5.0 mmol/L, with severity categorisation. RAASi discontinuation defined as ≥ 48 h without administration. Mortality risk associated with RAASi cessation was assessed using Cox proportional hazards models.ResultsAmong 129,172 patients with potassium measurements, 49,011 were hospitalised. Hyperkalaemia prevalence was 8.57% in the emergency department and 16.79% among hospitalised patients. Higher hyperkalaemia levels correlated with increased CKD and heart failure. RAASi use was more common in hyperkalaemic patients, with higher discontinuation rates during hospitalisation (36% with potassium 5–5.5 mmol/L; 61% with potassium > 6.5 mmol/L). By discharge, 32% of patients had RAASi stopped, and 2% doses reduced. Discontinuation of RAASi was associated with 37% worse survival probability.ConclusionRAASi cessation was greater with hyperkalaemia and associated with increased mortality in hospitalised patients. Reinstitution of RAASi after hospital discharge, or alternative management of hyperkalaemia if maintained on RAASi therapy, may improve clinical outcomes.

Association Between Long- Versus Short-Acting Angiotensin II Receptor Antagonists and Hypotension During Anesthesia Induction: A Retrospective Study.

The withdrawal or continuation of angiotensin II receptor blockers (ARBs) before surgery continues to be debated. We hypothesized that this is because ARBs with different half-lives have not been studied individually. This retrospective study aimed to clarify whether the degree of hypotension during anesthesia induction differs among ARBs with different half-lives. We included patients who received general anesthesia with regular oral administration of telmisartan (group T) or valsartan (group V), which have half-lives of approximately 24 and 6 hours, respectively. The frequency of hypotension and vasopressor frequency and dose during anesthesia induction were compared between the two groups. At our hospital, ARBs were withdrawn on the day of surgery in all patients. Groups T and V included 190 and 132 patients, respectively. Patient backgrounds in group V were significantly more strongly associated with the use of calcium channel blockers. No significant differences were observed in the use of other concomitant antihypertensive medications, cardiovascular complications, or renal function. The time during which the mean arterial blood pressure was < 60 mmHg during anesthesia induction was significantly greater in group T than in group V (11 min vs. 7 min, P=0.030). The proportion of patients who used vasopressors was significantly higher in group T than that in group V (74.2% vs. 56.0%, P < 0.001). Patients taking telmisartan showed more hypotensive during the induction of general anesthesia than those taking valsartan, even after withdrawal on the day of surgery.

Medicine Usage for Hypertension Management in Type 2 Diabetes Patients in the Rural-Urban Fringe Zone, Suzhou City, Jiangsu Province, China.

Medicine is critical for blood-pressure control in patients with type 2 diabetes mellitus (T2DM), for evaluation of treatment patterns and effects would offer baselines for future health services. A cross-sectional study was conducted from August 2018 to January 2021 in the urban-rural fringe zone of Suzhou City, Jiangsu Province, China. Blood pressure and antihypertensive medication use were collected from T2DM patients combined with hypertension (HTN). Using systolic blood pressure (SBP) and diastolic blood pressure (DBP) <140/85mmHg as HTN controls, medicine usage patterns were analyzed. Among the 931 T2DM patients with HTN, 333 (37.0%, 95% CI: 33.8%-40.2%) had HTN controlled with SBP and DBP of <140/85mmHg. Partial following the medicine recommendations for HTN control were observed in this zone, and calcium channel blocker (CCB), angiotensin II receptor blocker (ARB), diuretics and β-receptor blocker (Βeta-blocker) were the most frequently used ones, especially for CCB and ARB, which accounted for 67% (625/931) and 55% (509/931), respectively. For combination usage, complete adherence to the recommendation was observed, ie, ARB + CCB and ARB + diuretics were listed as the top two, accounting 30% (282/931) and 16% (153/931), respectively. Combination therapies had HTN control rates ranging from 31.1% to 39.1%, lower than those of monotherapy (>40%). In monotherapies, CCB had control rate of 41.2% (115/279, 95% CI 35.4%-47.2%), higher than combination (31.9%, 105/329, 95% CI 26.9%-37.3%), as well as ARB; the single reagent had control rate of 42.0% (95% CI 33.7%-50.7%), higher than combination (32.2%, 95% CI 27.4%-37.3%). More than 60% of T2DM patients had blood-pressures above the target level and the pattern of medications for HTN control in T2DM patients followed the recommendation of the authorities; however, the effects were not as expected, and more antihypertensive medicines or combinations would not raise the HTN control rate.

Primary Medication Adherence in Medicare Beneficiaries Prescribed Sacubitril-Valsartan or Renin-Angiotensin System Blockers for Heart Failure with Reduced Ejection Fraction

BackgroundSacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) that is now preferred over angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin-II-receptor blockers (ARBs) for treating heart failure with reduced ejection fraction (HFrEF). Primary medication adherence to a costly brand-name ARNI, compared to inexpensive generic ACE-Is or ARBs, is unknown. MethodsThis cohort study used a linked database of electronic health records and Medicare fee-for-service claims from a large integrated health care system in Boston to compare primary medication adherence among Medicare beneficiaries with HFrEF newly prescribed sacubitril-valsartan, those newly prescribed a generic ACE-I or ARB, and those switching from an ACE-I or ARB to sacubitril-valsartan. The primary outcome was the proportion of individuals who filled their first prescription for any ARNI, ACE-I, or ARB within 90 days; a secondary outcome was the mean number of days to first fill. We used logistic regression to adjust for variations in patient characteristics, including demographics, comorbidities, medication use, and qualification for subsidized out-of-pocket costs. ResultsAmong 50 new sacubitril-valsartan prescription recipients, 33 (66%) demonstrated primary adherence at 90 days, compared to 141 of 231 (61%) new ACE-I or ARB prescription recipients (adjusted odds ratio 1.32, 95% CI 0.63 to 2.73, p=0.51). The mean time to first fill was 18 days for those prescribed sacubitril-valsartan and 9 days for those prescribed generic ACE-Is or ARBs (p<0.001). By contrast, primary adherence at 90 days was higher (329 of 364, 90%) among those who switched from a generic ACE-I or ARB to newly prescribed sacubitril-valsartan. ConclusionsIn this small, single-center cohort study of Medicare beneficiaries with HFrEF, there was no difference in primary medication adherence among individuals newly prescribed sacubitril-valsartan and those newly prescribed generic ACE-Is or ARBs, although it took sacubitril-valsartan prescription recipients longer to fill their medication. Adherence was high among patients switching from an ACE-I or ARB to sacubitril-valsartan, suggesting that this switch was not associated with interruptions in renin-angiotensin blockade.

Lower Risk of Alzheimer’s Disease and Related Dementias associated with Angiotensin Receptor II Blockers (ARBs) treatment for individuals with Hypertension in High‐volume Claims Data

Lower Risk of Alzheimer’s Disease and Related Dementias associated with Angiotensin Receptor II Blockers (ARBs) treatment for individuals with Hypertension in High‐volume Claims Data

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.

A case of PLA2R-positive membranous nephropathy with subsequent development of IgG4-related disease.

Membranous nephropathy (MN) is a common cause of adult-onset nephrotic syndrome. It is also known as a minor but established renal manifestation of Immunoglobulin G4-related disease (IgG4-RD). Previous reports suggest that MN can also be an initial manifestation of IgG4-RD, all of which are phospholipase A2 receptor (PLA2R)-negative MN. We describe a case of PLA2R-positive MN that subsequently developed other manifestations of IgG4-RD. A 60-year-old male with nephrotic syndrome was diagnosed as primary MN with positive staining for PLA2R on the initial renal biopsy, which remained in partial remission with supportive therapy using angiotensin II receptor blocker (ARB) without steroid. About 1year later, a renal mass was detected during an annual checkup, and contrast-enhanced computed tomography revealed low-density masses in bilateral kidneys and the head of the pancreas. The findings of endoscopic biopsy of the pancreatic mass were consistent with autoimmune pancreatitis (AIP) and the second renal biopsy showed the findings of MN with tubulointerstitial nephritis, both of which led to a diagnosis of IgG4-RD. The second renal biopsy also showed positive PLA2R. The patient received oral glucocorticoid therapy for IgG4-RD, which improved IgG4-related AIP and renal masses and also resulted in complete remission of MN. To our knowledge, this is the first reported case of PLA2R-positive MN with subsequent development of IgG4-RD. It is sometimes difficult to determine whether PLA2R-positive MN occurring with IgG4-RD is primary MN or secondary MN associated with IgG4-RD. The possibility of developing IgG4-RD should be considered even when preceding MN is PLA2R-positive, suggesting of primary MN.

Avoiding anti-inflammatories: a randomised controlled trial testing the effect of an eHealth information package on primary healthcare patient medication knowledge and behaviour in Aotearoa New Zealand

BackgroundPatient medication knowledge and health literacy affect patient safety. Taking angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin II receptor blockers (ARBs), with diuretics and non-steroidal anti-inflammatory medications (NSAIDs) is nephrotoxic. Patients...

Targeting the Renin-Angiotensin System in Obesity-Driven Hyperlipidemia and Hypertension

The renin-angiotensin system (RAS) plays a crucial role in the regulation of blood pressure, fluid balance, and lipid metabolism. Dysregulation of the RAS has been implicated in the pathogenesis of obesity-driven hyperlipidemia and hypertension, two major components of metabolic syndrome that significantly increase the risk of cardiovascular disease. In obese individuals, increased adipose tissue promotes local activation of the RAS, leading to heightened angiotensin II (Ang II) activity, oxidative stress, inflammation, and impaired lipid metabolism. These pathological mechanisms contribute to both elevated blood pressure and abnormal lipid profiles. Targeting the RAS through angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and novel agents offers therapeutic potential in reducing obesity-associated hypertension and hyperlipidemia. This review discusses the molecular mechanisms linking obesity to RAS overactivation, examines current pharmacological strategies, and explores emerging therapeutic options aimed at modulating the RAS in the context of obesity-driven cardiometabolic disorders. Keywords: Renin-angiotensin system, obesity, hyperlipidemia, hypertension, angiotensin II, ACE inhibitors, ARBs, metabolic syndrome, cardiovascular disease.

Abstract 220: Cerebral Angioedema in a Patient with Refractory Hypertension and Intracerebral Hemorrhage

Introduction/Purpose There is emerging evidence to implicate bradykinin in the development of cerebral edema. In the periphery, its association to the development of angioedema is well known. However, the relationship of peripheral angioedema to the development of cerebral angioedema is not well established. Angioedema may occur in patients receiving antihypertensive medication, and alteplase for acute ischemic stroke (1), however, the concurrent involvement of cerebral vasculature is not well studied. Moreover, the connection with cerebral edema ‐ cytotoxic or vasogenic ‐ remains poorly understood. Here we present a patient with an intracerebral hemorrhage (ICH) in the setting of refractory hypertension, who developed angioedema, and ultimately fulminant cerebral edema. We aim to investigate whether angioedema may extend beyond a systemic response and into the cerebral vasculature, contributing to further neurological compromise. Materials/Methods A retrospective review was conducted for one patient. Data, including history, exam, imaging, and clinical interventions were analyzed. All identifiers were removed. Results A 51‐year‐old African American woman with a medically refractory hypertension on multiple home medications presented with aphasia, and a blood pressure of 220/110 mm Hg. An initial non contrast head CT revealed a 60‐cc left basal ganglia intracerebral hemorrhage. CTA of the head and neck were negative for an underlying structural abnormality. She required intubation soon after presentation due to obtundation. No interval re‐hemorrhage was noted on repeat head CT. A contrast enhanced MRI was also unrevealing. 48 hours later she was noted to have orolingual edema and an angiotensin converting enzyme inhibitor (ACEi) and diltiazem were discontinued. In the ensuing days, due to difficult to control hypertension despite being on multiple antihypertensives, an angiotensin II receptor blocker (ARB) was introduced. However, this was discontinued and reintroduced several days later only to be discontinued again due to orolingual edema. She also had a failed extubation attempt due to hypoxemia and stridor, and received FFP, decadron, and racemic epinephrine. 2 days later she developed bradycardia and had neurologic deterioration progressing from initial right hemiparesis to complete unresponsiveness on examination. A noncontrast head CT showed no interval re‐hemorrhage but did show new areas of hypodensity involving the bilateral occipital lobes, the brainstem, the left temporal lobe, and uncal herniation. Hypertonic saline was started, however the patient progressed to brain death. Conclusion This case highlights the potential link between systemic angioedema, and fulminant cerebral edema and rapid neurologic decline. Previous literature has described potentially parallel mechanisms behind peripheral angioedema and cerebral edema (2). Angioedema may also influence progression from vasogenic to cytotoxic cerebral edema. As vasogenic edema develops, the increased tissue pressure can lead to ischemia and exacerbate cytotoxic edema (3). The significance of posterior circulation involvement is noteworthy, as ischemic infarctions here can lead to neurological deficits and are associated with vasogenic edema due to blood‐brain barrier disruption, such as in posterior reversible encephalopathy syndrome (PRES). Further investigation is required to explore acute intracerebral effects of angioedema. Physicians should consider cerebral angioedema in patients with both peripheral angioedema and neurological deterioration.