Angiotensin II Receptor Blockers Research Articles

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.

Cardiovascular profile drugs and the state of periodontal tissues

People with CVD, mostly over 50 years of age, regularly take medications such as beta-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), statins and acetylsalicylic acid (ASA). Periodontal tissue disease (PTD) occurs in the age group 35–44 years in 60% of cases, in the group of people 65–74 years – about 70%, that is, in that period of life when cardiovascular disease (CVD) begins to develop and progress. Some cardioprotective drugs, such as antihypertensives, cause xerostomia. Medication-induced xerostomia is one of the common causes of oral health problems in older adults who are on long-term drug therapy. Xerostomia is a common debilitating condition that causes problems such as dysphagia, loss of taste, and oral pain, as well as increasing the risk of tooth decay and oral infections. Drug-induced gingival overgrowth is an abnormal hypertrophy of the gingiva that can be caused by a number of medications, including calcium channel blockers. Drug-induced gingival overgrowth is characterized by the accumulation of connective tissue that primarily affects the anterior regions of the upper and lower jaw, and also causes problems with oral hygiene, which leads to susceptibility to infections and periodontal disease and can lead to tooth loss. Anticoagulants used in CVD due to the risk of bleeding require special approaches in the prevention and therapy of periodontal tissue disease. The possibilities of using statins in PTD due to their pleiotropic properties, independent of hypolipidemic action. The review article is devoted to the influence of drugs of cardiovascular profile on the state of periodontal tissues and mechanisms of development of side effects, as well as the possibilities of using statins taking into account their pleiotropic effects.

Elegibility for Sacubitril/Valsartan in italian clinical practice: insights from the OPTIMA-HF registry

Abstract Background/Introduction Guidelines strongly recommend patients with heart failure with reduced ejection fraction (HFrEF) be treated with multiple medications proven to improve clinical outcomes, as tolerated. Among them, angiotensin receptor blocker/neprylisin inhibitor (ARNi) are the foundation of neuro-hormonal blockade in patients with HFrEF, however the degree to which gaps in this medication use and dosing persist in outpatient practice is unclear. Purpose To assess the proportion of patients with HFrEF who are eligible for ARNi based on the PARADIGM-HF trial criteria and the association between eligibility and baseline characteristics. Methods The OPTIMA-HF (Optimization of Therapy in the Italian Management of Heart Failure) registry included outpatients in Italy with chronic HFrEF receiving at least 1 oral medication for management of HF. Patients were characterized by baseline use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)/ARNI, beta-blocker, mineralocorticoid receptor antagonist (MRA) and sodium glucose co-transporter II inhibitor (SGLT2i). Patient-level factors associated with medication use were examined. Results Outpatients with HFrEF from 29 ambulatory cardiology practices and university hospitals in the OPTIMA-HF registry recruited between January 2022 and September 2023 were included. Of 1291 patients, 1018 (79%) met the PARADIGM-HF criteria and 949 of them (93%) were on ARNi. Of the enrolled patients, 342 (27%) were not on ARNi, however only 129 (38%) did not met the PARADIGM-HF inclusion criteria for ARNi prescription. Reasons for not meeting PARADIGM-HF criteria were no beta-blocker background therapy (22%), hyperkalemia (4%), hypotension (15%), chronic kidney disease (65%) and hyperkalemia (79%). In a logistic regression model not being on ARNi was associated with older age, chronic kidney disease, not being on cardiac resynchronization therapy, lower systolic blood pressure, lower BMI, and higher PAPs (Figure), representing the picture of a more fragile patient net of compliance with the PARADIGM-HF criteria. Conclusions Among outpatients with HFrEF in the OPTIMA-HF Registry, 79% met the PARADIGM-HF criteria. Strategies to improve guideline-directed use of HFrEF medications remain urgently needed, and these findings may inform targeted approaches to optimize outpatient medical therapy.

Modern heart failure treatment is superior to conventional treatment across the left ventricular ejection spectrum: Real-life data from the Swedish Heart Failure Registry 2013-2020

Abstract Background Heart failure (HF) is a clinical syndrome characterized by high mortality and morbidity. In 2016, Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), was recommended as a new treatment option for HF in patients with HFrEF. In the 2021 European Society of Cardiology guidelines for treatment of HFrEF patients Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were introduced because they demonstrated significantly reduced HF events or cardiovascular (CV) mortality. Since ARNI and SGLT2i were introduced to treat HF, its therapeutic regimen has modernized from previous treatment with beta-blocker (BB) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) with mineralocorticoid receptor antagonist (MRA) as added-on in HF with reduced ejection fraction (HFrEF). Purpose This study is aimed to compare effectiveness of modern therapy including ARNI and SGLT2i with conventional heart failure treatment. Conventional HF treatment includes (BB, ACEi/ARB, with or without MRA) and modern heart failure treatment (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i) in real-world. Methods This observational study (2013-2020), using the Swedish HF Registry, involved 20,849 HF patients. Patients received either conventional (BB, ACEi/ARB, with/without MRA, n=20,140) or modern (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i, n=709) treatment at the index visit. The endpoints were all-cause and cardiovascular (CV) mortality. Results Modern HF therapy was associated with a significant 28% reduction in all-cause mortality compared to conventional HF treatment (adjusted HR [aHR]: 0.72 (95% CI 0.54 - 0.96), p=0.024), and had 33% reduced all-cause mortality (aHR: 0.67 (95% CI 0.48 - 0.94), p=0.019) within 2 years of index registration. Similarly, modern HF therapy was associated with a significant 62% reduction in CV mortality compared to conventional HF treatment (aHR: 0.38 (95% CI 0.21 - 0.68), p=0.0013). In addition, we found a 58% reduced CV mortality (aHR 0.42 (95% CI 0.22 - 0.79), p=0.0067) within 2 years of index registration. In the propensity score 1:1 matched cohort in which ARNI was included in the matching procedure, i.e., no ARNI was used in any of the two treatment groups and the effect of SGLT2i was the target assessment. The results were associated with a statistically significant risk reduction of 42% in all-cause mortality in the modern HF treatment group compared to the conventional treatment group (aHR: 0.58 (95% CI 0.36 - 0.94), p=0.028), and a 49% (aHR: 0.51 (95% CI 0.29 - 0.89), p=0.018) risk reduction within 2 years of index registration. Conclusion This study demonstrates that modern HF therapy in a real-world Swedish HF population is associated with a statistically significant risk reduction in all-cause and CV mortality, regardless of EF, sex, age, eGFR, and etiology of HF compared to conventional HF therapy.Central Illustration

Guideline-directed medical therapy patterns in heart failure with reduced ejection fraction: the OPTIMA-HF registry

Abstract Background/Introduction European guidelines strongly recommend an optimized pharmacological treatment in patients with heart failure with reduced ejection fraction (HFrEF) with a fast introduction of the four-pillars. Purpose Aim of the Optimization of Therapy in the Italian Management of Heart Failure [OpTIMa-HF] Registry was to collect data on HF patients to describe the current Italian population of HF patients with a specific focus on HFrEF treatment adherence and prescription rates, according to the most recent European Guidelines. Methods OPTIMA-HF is an observational, cross-sectional, multicenter, real-life study conducted in two different clinical settings: HF outpatients’ clinics of Italian University Hospitals and territorial Italian Cardiology outpatients’ services, that enrolled patients with chronic HFrEF receiving at least 1 oral medication for management of HF. Patients were characterized by baseline use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI), beta-blocker, mineralocorticoid receptor antagonist (MRA) and sodium glucose co-transporter II inhibitor (SGLT2i). Patient-level factors associated with medication use were examined. Results Overall, 1390 patients from 29 ambulatory cardiology practices and university hospitals were included. Mean age was 69.5 ± 11.9 years, 24% were female, and median EF was 33 (28-37). Among enrolled patients, 72.2% were prescribed ARNI, 17.1% ACEI/ARB, 95% beta-blocker, 75.5% MRA and 63% SGLT2i therapy (Figure 1). Despite high prescription rates for each single class, a still not sufficient number of patients was on treatment with all four pillars, in particular 40.4% considering the presence ARNI and 6.2%. When medications were prescribed, few patients were receiving target doses of ACEI/ARB (31.7%), ARNI (16%), and beta-blocker (33.3%), whereas a higher proportion were receiving target doses of MRA therapy (38%), and all were receiving target dose for SGLT2i. Among patients eligible for all classes of medication, only 1.1% were simultaneously receiving target doses of ACE/ARB/ARNI, beta-blocker, MRA and SGLT2i. Prescription rates did not significantly differ between the type of center (University Hospital vs. territorial Cardiology outpatients’ services). As regards patients not on treatment with any of the four pillars, a small but still present amount of patients had no contraindications to these drugs (Figure 1). Conclusions In this contemporary outpatient HFrEF Italian registry, significant high prescription rates of the four-pillars were observed, however therapy combination rate is still not sufficient and drugs' titration need to be implemented to receive the greatest benefits from an optimized treatment. Strategies to improve guideline-directed use of HFrEF medications remain urgently needed, and these findings may inform targeted approaches to optimize outpatient medical therapy.

Prognostic determinants in patients with heart failure with reduced ejection fraction after a first hospitalisation for acute heart failure. COMFE registry

Abstract Introduction The clinical characteristics and determinants for prognosis of patients with a first hospitalisation for heart failure (HF) with reduced left ventricular ejection fraction (LVEF <40%) are poor described and show heterogeneous results that need major investigation. Purpose The aim of our study was to identify the clinical characteristics, prognosis and their main determinants in a prospective registry of patients with HF and reduced LVEF with a first hospital admission for acute heart failure, prognosis and their main determinants in a prospective registry in these patients. Methods We carried out a prospective registry in 2 University Hospitals of patients admitted to cardiology department due to first-time HF hospitalisation with reduced LVEF. 231 admitted consecutively between March 2021 and September 2022 were included, with a mean follow-up of 381 days. Continuous variables were represented as median (interquartile range) and categorical variables as percentage %. A multivariate logistic regression was performed in which age, sex, comorbidities, treatment, rhythm at discharge and improvement in LVEF were included; and using the Wald method, the predictors of rehospitalization and/or death were identified. Data were analysed using SPSS v. 25.0. Results The main baseline characteristics are shown in Table 1. The population had a median age of 71 years, 75% were men, with a high prevalence of arterial hypertension (HBP) (69%) and hyperlipidemia (57%). Quadruple therapy (Na-Glucose cotransporter 2 inhibitor [SGLT2i], Beta-Blocker, mineralocorticoid receptor antagonist [MRA] and angiotensin receptor-neprilysin inhibitor [ARNI], angiotensin converting enzyme inhibitor [ACEi] or Angiotensin-II receptor blocker [ARB]) was achieved in 57% at discharge. The dynamics of NTproBNP was studied from admission to completed up-titration, observing an average reduction of 37% and 32% met the criteria for improved LVEF after. The etiology is described in Figure 1a, with ischemic heart disease being the most represented (31%). Multivariate Cox regression for the combined event of readmission/death from any cause showed that treatment with SGLT2i (OR 0,48 [CI 95%: 0,23-0,98 p:0,04]) and Beta-Blocker (OR 0,35 [CI 95%: 0,14-0,87 p:0,02]) at discharge and improved LVEF (OR 0,33 [CI 95%: 0,15-0,72 p:0,006]) were protective predictors against the event; but diabetes mellitus (DM) was a predictor of a worse prognosis (OR 2,9 [CI 95%: 1,52-5,5 p:0,001]) Fig. 1b. Conclusions Patients with a first admission for HF with reduced LVEF constitute a heterogeneous clinical group. Improvement in LVEF after drug up-titration and treatment with SGLT2i and Beta-blocker are independently associated with a better prognosis. Our findings may have implications for their clinical management.Table 1Figure 1

Systematic Review: Comparative Efficacy and Safety of Losartan vs. Candesartan for the Treatment of Hypertension

Hypertension is one of the most significant modifiable risk factors for cardiovascular disease (CVD) and remains a leading cause of morbidity and mortality globally. Effective management of hypertension is essential for preventing comp lications such as stroke, myocardial infarction, and heart failure. Angiotensin II receptor blockers (ARBs) like losartan and candesartan are well-established therapeutic options for blood pressure (BP) control and are widely prescribed due to their favorable side-effect profiles and organ-protective properties. Despite being members of the same drug class, these ARBs differ in their pharmacokinetics, receptor binding affinity, and clinical efficacy. This systematic review aims to provide a detailed comparison of the efficacy and safety of losartan versus candesartan in managing hypertension. We conducted a comprehensive search of the PubMed, Embase, and Cochrane databases, retrieving studies published from 2000 to 2024 that compared the two ARBs directly in hypertensive populations. A total of 25 randomized controlled trials (RCTs) and observational studies, comprising more than 12,000 participants, were included in the analysis. The primary outcomes evaluated were the reduction in systolic and diastolic blood pressure, cardiovascular event prevention, and adverse event profiles. The results suggest that both losartan and candesartan effectively lower BP, but candesartan consistently demonstrated greater reductions in both systolic and diastolic BP compared to losartan. Candesartan also appeared to have superior cardiovascular outcomes, with a lower incidence of major cardiovascular events such as stroke, myocardial infarction, and heart failure hospitalizations. The safety profiles of both drugs were comparable, though losartan was associated with a slightly higher incidence of cough and discontinuation due to adverse events. Overall, candesartan may offer a slight clinical advantage over losartan, particularly in patients requiring more potent or sustained BP control. However, both drugs remain valuable options in the management of hypertension. Further long-term studies are recommended to confirm these findings and to investigate the potential benefits of each drug in specific patient subgroups.

Advancing Community Care and Access to Follow-Up after Acute Kidney Injury Hospitalization: A Randomized Clinical Trial.

Key Points A risk-guided intervention improved adherence to processes of care for AKI survivors.Further supports are necessary to improve uptake of processes of care for AKI survivors in primary care. Background AKI is associated with development and progression of CKD. Gaps in recommended care for CKD are common after AKI. Methods In this randomized controlled trial conducted in Alberta, Canada, we allocated adults hospitalized with Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or greater AKI to a risk-guided, transition of care intervention versus usual practices at the time of hospital discharge. For people in the intervention group, we used a validated risk index to predict risk of severe CKD after AKI. People at low risk (<1%) received patient education alone. People at medium risk received additional clinical guidance, provided to their primary care physician. People at high risk (>10%) were referred to nephrology. The primary outcome was the proportion of patients who received treatment with an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB), statin, and nephrology specialist follow-up within 90 days of discharge. Results One hundred fifty-five patients were recruited; the mean (SD) age was 60 (15) years, 91 (60%) were male, and 96 (62%) had eGFR <60 ml/min per 1.73 m2 or urine albumin-creatinine ratio >30 mg/g at discharge. The proportion of participants who received ACE-I/ARB, statin treatment, and nephrologist follow-up was 28% in the intervention group versus 3% in the usual care group (absolute risk difference [RD], 25%; 95% confidence interval [CI], 15% to 36%). The use of ACE-I or ARB in participants with urine albumin-creatinine ratio >300 mg/g or diabetes was greater in the high-risk group with the intervention versus usual care (RD, 37%; 95% CI, 6% to 67%), as was statin use among those with CKD (RD, 30%; 95% CI, 5% to 56%) and nephrologist follow-up for those with sustained eGFR <30 ml/min per 1.73 m2 at discharge (RD, 78%; 95% CI, 56% to 100%). Hyperkalemia was more frequent in the intervention group (RD, 10%; 95% CI, 9% to 19%). Conclusions A risk-guided intervention for patients hospitalized with AKI increased recommended processes of care for CKD for high-risk patients after hospital discharge. Clinical Trial registry name and registration number: Improving Post Discharge Care after Acute Kidney Injury (AFTER AKI), NCT02915575.

Dapagliflozin for rheumatic musculoskeletal disease in patients with chronic kidney disease.

To elucidate the effectiveness of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor, on renal function in patients with rheumatic musculoskeletal diseases complicated by chronic kidney disease (CKD) and identify factors associated with the response to dapagliflozin. We conducted a retrospective analysis of patients with rheumatic musculoskeletal disease and CKD who were treated with dapagliflozin for more than a year. The good response was defined as an improvement in the estimated glomerular filtration rate (eGFR) slope per year after dapagliflozin treatment compared to that before treatment. Additionally, we investigated the response rate and its predictive factors. In this analysis, 43 patients were included. The average eGFR slope demonstrated a significant improvement after dapagliflozin treatment compared to that before the treatment (0.04 vs -0.55 mL/min/1.73m²/year, p=0.001). A good response rate was 69.8% and was associated with low average levels of C-reactive protein, a high frequency of angiotensin II receptor blocker (ARB) use, and a low frequency of tacrolimus use compared to non-response (0.08 ± 0.18 vs 0.25 ± 0.29 mg/dL, p=0.03; 80.0% vs 38.4%, p=0.01; 10.0% vs 76.9%, p<0.01). Dapagliflozin is effective for rheumatic musculoskeletal diseases patients with CKD for preventing deterioration of renal function. Antihypertensive treatment with ARBs and inflammation control without tacrolimus was associated with a high likelihood of favorable response to dapagliflozin.

Real-world experience in initiation of treatment with the selective cardiomyosin inhibitor mavacamten in an outpatient clinic cohort during the 12-week titration period.

Lately, mavacamten emerged as a new therapeutic option for symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM). Clinical trials revealed reduction of serum biomarkers, and left ventricular outflow tract (LVOT) obstruction, as well as an improvement in clinical symptoms and exercise capacity. Nevertheless, clinical experience and manageability of patients in a real-world setting is still lacking. 22 patients with symptomatic oHCM (54.5% male, age 58.5 ± 16.2years) and elevated LVOT gradients were started on mavacamten between March 2023 and June 2024. All patients were New York Heart Association (NYHA) class II or higher. Seven patients were excluded from primary analysis due to comedication with Angiotensin-converting-enzyme-inhibitors or Angiotensin-II receptor blockers. Cardiac imaging, laboratory work-up and clinical evaluation were assessed at three visits during the 12weeks initiation phase; Dosing of mavacamten was adjusted according to manufacturer's recommendations. At 12weeks, the majority of patients described a significant improvement of their quality of life. Work-up at 12weeks revealed a significant reduction of serum biomarkers and LVOT gradients. In four patients, mavacamten needed to be temporarily paused due to clinical complaints or transient left ventricular ejection fraction deterioration below 50% with subsequent full recovery. We provide first insights into the usage of mavacamten in oHCM patients during the titration period in a real-world setting. Clinical findings are in line with previous clinical trials. In accordance with current recommendations, we highlight the need for standardized follow-up of patients on mavacamten treatment.

Effectiveness of a fixed combination of empagliflozin with metformin in reduction of cardiovascular risk in patients with uncontrolled arterial hypertension and decompensated type 2 diabetes mellitus

Objective is to study the effectiveness of a fixed combination of empagliflozin and metformin in reducing cardiovascular risk in patients with uncontrolled arterial hypertension (AH) and decompensated type 2 diabetes mellitus (DM). Materials and methods. 36 patients with uncontrolled AH and decompensated type 2 diabetes mellitus aged 45 to 60 were examined. Before inclusion in the study, all patients received standard antihypertensive (angiotensin‑converting enzyme (ACE) inhibitor or angiotensin‑II receptor blocker (ARB) in combination with a calcium channel blocker and a thiazide‑like diuretic), glucose‑lowering (metformin) and hypolipidemic (atorvastatin) therapy. However, target levels of blood pressure (BP), glycated haemoglobin (HbA1c) and lipids were not achieved. After the initial examination, all patients were prescribed a fixed combination of empagliflozin and metformin at a dose of 12.5 mg/1000 mg 1—2 times a day, and antihypertensive and hypolipidemic therapy was continued. Re‑examination was carried out after 20 weeks. In the work, a statistical analysis of the obtained data was carried out using standard methods using Microsoft Excel 7.0 and SPSS 19.0 application packages. Results. The transfer of the examined patients from previous ineffective hypoglycemic therapy to a fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy made it possible to achieve the target levels of HbA1c in 69% of patients and target BP levels in 64%. The frequency of reaching target BP levels in the subgroup of patients who received ARB was significantly higher than in the subgroup of patients who received ACE inhibitors. The specified therapy contributed to a significant reduction in body weight, reaching the target levels of low‑density lipoprotein cholesterol (LDL‑C) and non‑high‑density lipoprotein cholesterol (Non‑HDL‑C) in more than a third of patients, and reducing the severity of albuminuria in some patients. The tested therapy, in general, led to reduction in cardiovascular risk and did not cause side effects that could lead to discontinuation of treatment. Conclusions. The fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy in patients with uncontrolled hypertension and decompensated type 2 diabetes mellitus contributed to the achievement in the vast majority of patients of the target levels of HbA1c in the blood and BP levels, reduced body weight, positive changes in lipid metabolism and kidney function, and demonstrated the possibility of a significant reduction in cardiovascular risk. A more pronounced decrease in BP was detected in the case of a fixed combination of empagliflozin and metformin with ARB compared to ACE inhibitors in this category of patients.

8707 Are We Adequately Prescribing Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) Or Glucagon-Like Peptide 1 Receptor Agonist (GLP-1 RA) In Patients With Type 2 Diabetes Mellitus (T2DM) And Established Atherosclerotic Cardiovascular Disease (ASCVD) Or Chronic Kidney Disease (CKD) In An Outpatient Setting: A Community Center Experience

Abstract Disclosure: R.K. Maan: None. A. Sawhney: None. A. Hayat: None. S. Kc: None. A. Madan: None. S. K c: None. L. Williams: None. A. Zweben: None. A. Rana: None. Introduction: The American Diabetes Association (ADA) recommends prescribing Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) or Glucagon-Like Peptide 1 Receptor Agonist (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and established Atherosclerotic Cardiovascular Disease (ASCVD) or Chronic Kidney Disease (CKD) for its cardiovascular benefits. Methods: Our retrospective study analyzed data from 511 T2DM patients who visited the outpatient clinic between 7/1/22 to 6/30/23. Using Microsoft Excel, we assessed adherence to ADA guidelines by collecting data for SGLT2i, GLP-1 RA and statin prescriptions, urine microalbumin creatinine ratio measurements, and appropriate management of albuminuria. The study also investigated patients on dipeptidyl peptidase-4 inhibitors (DPP-4i) who were eligible for SGLT2i or GLP-1 RA. Results: Out of the 511 patients, 478 were eligible for SGLT2i or GLP-1 RA, and only 60% were prescribed these medications. Out of 479 patients eligible for statin prescription, only 85% were on it. Albuminuria was appropriately managed in 76% of eligible patients with Angiotensin-Converting Enzyme Inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARBs). Additionally, 8 out of 11 patients on DPP-4i were eligible for SGLT2i or GLP-1 RA. Conclusion: We concluded that 60% of the patients eligible for SGLT2i or GLP-1 RA were prescribed the medication in our outpatient settings. The barriers identified were issues with insurance prior authorization and knowledge gaps. We aim to improve adherence to guidelines through multifaceted education strategies combined with audits and feedback.

Association between risk of Alzheimer’s disease and related dementias and angiotensin receptor Ⅱ blockers treatment for individuals with hypertension in high-volume claims data

Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer's disease and related dementias (AD/ADRD) and cognitive decline have been inconclusive. Individuals with hypertension who do not have any prior ADRD diagnosis were included in this retrospective cohort study from Optum's de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood-brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan-Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses. From 6,390,826 individuals with hypertension, there were 1,839,176 ARB users, 3,366,841 non-ARB AHM users, and 1,184,809 AHM non-users. The unadjusted KM curve showed that ARB users had lower cumulative hazard than other AHM users or AHM non-users (P<0.0001). In Cox PH analysis, ARB users showed a 20% lower adjusted hazard of developing ADRD compared to angiotensin-converting enzyme inhibitor (ACEI) users and a 29% and 18% reduced hazard when compared to non-ARB/ACEI AHM users and AHM non-users (all P<0.0001). Consumption of BBB-crossing ARBs was linked to a lower hazard of ADRD development than non-BBB-crossing ARBs, undetermined ARBs, and non-consumption of AHMs by 11%, 25%, and 31% (all P<0.0001). This study suggests that ARBs are superior to ACEIs, non-ARB/ACEI AHMs, or non-use of AHMs in reducing the hazard of ADRD among patients with hypertension. Also, BBB-permeability in ARBs was associated with lower ADRD incidence. There is no cure for AD, ADRD, or vascular dementia; hence, these findings are significant in preventing those disorders in an inexpensive, convenient, and safe way. Limitations in claims data should be considered when interpreting our findings. This research was supported by the National Institute on Aging grants (R01AG084236, R01AG083039, RF1AG072799, R56AG074604).

Angiotensin II receptor blockers and their applications in orthopaedic surgery and musculoskeletal medicine.

Angiotensin II receptor blockers (ARBs) are commonly prescribed for hypertension and heart failure, and have well-described antifibrotic properties throughout medical literature. The etiology and pathogenesis of fibrosis is biologically complex with a multitude of factors playing a role in the process. Consequently, pathologic fibrosis may be significant within orthopaedics contributing to post-operative stiffness and, ultimately, negative patient outcomes. The pharmacology of ARBs has been described to combat fibrosis in preclinical settings, while the literature of ARBs antifibrotic properties in relation to orthopaedics remains scarce. However, fibrosis is one of the primary factors contributing to tissue healing and functional recovery in the field of orthopaedic surgery. Fibrosis has specifically been described in relation to shoulder surgery, knee arthroplasty and hip arthroscopy. As such, outcomes of various orthopaedic surgeries are dependent upon a balance between tissue healing and stiffness, both of which may be mediated by a fibrotic response. Importantly, ARBs have recently emerged as a potential therapy to combat fibrosis-mediated stiffness in orthopaedic surgery patients. Thus, the following review article seeks to highlight the basic and clinical science of ARBs with emphasis on their implications and indications for orthopaedic surgery and musculoskeletal medicine.

Protocolo terapéutico de la diabetes mellitus tipo 2 con nefropatía

The protocol describes the therapeutic management of patients with type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), a frequent complication in 20%–40% of individuals with DM2. Treatment is based on blood pressure control (target<130/80mmHg); angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs) are recommended. For glycemic control, the glycosylated hemoglobin (HbA1c) level sought is individualized for each patient, but is generally below 7%, adjusting the medication according to the patient's estimated glomerular filtration rate (eGFR). Sodium-glucose cotransporter-2 (SGLT-2i) inhibitors and glucagon-like peptide-1 agonists (GLP-1a) are recommended for their renal and cardiovascular benefits. In addition, patients with CKD and DM2 should be treated with statins to reduce cardiovascular risk, avoiding drugs that increase the risk of hypoglycemia. Individualized treatment and frequent monitoring are essential, especially in patients with decreased eGFR and persistent albuminuria.

Successful Factors for Improving Aortic Remodeling with Thoracic Endovascular Repair and Bare Stent Extension

ObjectiveProximal ExTension to Induce COmplete ATtachment (PETTICOAT), which utilizes downstream bare metal stents for structural support, demonstrates potential, yet its adoption is limited by variable outcomes. This study elucidates the potential of PETTICOAT in aortic dissection, emphasizing the determinants that guide patient selection. MethodsA retrospective analysis of 60 patients who underwent full PETTICOAT for aortic dissections was conducted. A multivariate logistic regression model identified predictors of favorable aortic remodeling. Patients underwent standardized follow-up with CT scans to assess size, volumetric changes, and anatomical conditions. Selection criteria included full PETTICOAT application and a minimum three-month follow-up. Demographics, preoperative conditions, and procedural details were collected and analyzed. ResultsThe analysis identified predictors of favorable aortic remodeling, including age over 60, a larger downstream aorta stent graft, a smaller abdominal aorta (<450mm2), and oral angiotensin II receptor blocker (ARB) administration. Over a median 47.5-month follow-up, survival rates in the favorable remodeling (97.3%) and unfavorable groups (100%) were similar. Downstream aortic event-free survival rates did not significantly differ (89.2% vs. 73.9%), although the unfavorable group had a relatively higher incidence of distal stent-induced new entries (26.1% vs. 8.1%). ConclusionsThe PETTICOAT concept effectively enhances aortic remodeling in complex aortic dissections. Predictors for favorable remodeling, including age, stent graft sizing, aortic diameter, and ARB therapy, offer insights for optimizing patient selection. This approach improves survival outcomes, mitigates risks associated with untreated aortic segments, and provides a minimally invasive solution for aortic dissections. Despite some outcome variations, the technique holds promise for addressing the challenges of aortic dissections, with the potential for further refinement in patient selection and technique application.

Patient Adherence and Duration of Continuous Treatment With Various Arbs in Patients With Uncomplicated Arterial Hypertension in the USA Based on The Analysis of the Truven Health Analytics MarketScan Database.

To discuss two aspects that can be used to improve the adherence to therapy in patients with arterial hypertension (AH): 1) which of the angiotensin II receptor blockers (ARBs) provides the highest adherence rates; 2) how various factors influence adherence rates. An analysis of one of the world's largest clinical practice databases, Truven Health Analytics MarketScan (currently Merative MarketScan), was performed. The analysis included data on patients of both sexes aged 30 to 65 years who had been diagnosed with uncomplicated AH (at least once between March 1, 2012 and January 1, 2018) and prescribed monotherapy with one of ARBs. The exclusion criteria were heart failure and the treatment with two or more ARBs (simultaneously or sequentially) during the treatment period. Ultimately, the study included 717,099 patients with uncomplicated AH, who were divided into four groups based on the prescribed drug: azilsartan (n=4276), candesartan (n=6023), losartan (n=586,857), and valsartan (n=119,943). Adherence to treatment was evaluated by two parameters: duration of continuous therapy and medication possession ratio (MPR). The individual effect of each factor (specific ARB used for therapy, patient gender, age, initial ARB dose, patient co-payment per day of treatment) on the adherence to treatment was assessed using a regression analysis. The adherence to the ARB therapy was generally high. The MPR was the lowest in the azilsartan group and the highest in the candesartan group. However, the parameters that potentially influenced both the MPR and the duration of continuous therapy (patient's gender and age, initial ARB dose, co-payment size) differed significantly between the groups receiving different ARBs. The regression analysis showed that both adherence parameters and the duration of continuous therapy were higher in patients receiving candesartan than in patients receiving azilsartan, losartan or valsartan, when the effect on the adherence of other factors available for study (age, gender, initial dose of the drug, and the absolute size of co-payment for a day of therapy) was excluded. The lowest adherence to therapy was observed in the azilsartan treatment group (p&lt;0.01). The study provided data for comparing the adherence of patients with uncomplicated AH to the therapy with different ARBs. Further study of adherence to treatment will provide additional data that will allow an optimal selection of drugs for the treatment of AH in patients with potentially poor adherence.

Novel Insights into Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. As the leading cause of end-stage renal disease (ESRD) globally, DKD develops through a complex interplay of chronic hyperglycemia, oxidative stress, and inflammation. Early detection is crucial, with diagnosis based on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, and the use of nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on rigorous control of hyperglycemia and hypertension, aiming to mitigate disease progression. Despite therapeutic advances, DKD remains a leading cause of ESRD, highlighting the need for continued research to identify new biomarkers and innovative treatments.