Angiotensin Receptor Blocker Therapy Research Articles

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

Decreased Prevalence of New-Onset Adhesive Capsulitis in Patients Prescribed Angiotensin Receptor Blockers

Angiotensin receptor blockers (ARBs) are commonly prescribed antihypertensive agents that have well-known antifibrotic properties. The purpose of this study was to examine the association between ARB use and the rates of new-onset adhesive capsulitis as well as adhesive capsulitis requiring operative treatment. Using a large national insurance database, a randomly generated cohort of patients with at least 3 continuous months of ARB use between January 2010 and December of 2019 (n=1,000,000) was compared to a separate randomly generated cohort without ARB use (n=3,000,000) . Rates of newly diagnosed adhesive capsulitis and associated manipulation under anesthesia and/or arthroscopic capsulotomy were calculated over a one- and two-year period following the completion of at least 3 continuous months of ARB therapy. Rates were compared using multivariable logistic regression to control for demographics and comorbidities. Both unadjusted and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated and reported for each comparison. Statistical significance was set at P<0.05. The mean age in the ARBs cohort was 61.8 years (SD = 10.0), while in the control cohort, it was 54.8 years (SD = 12.3) (p < 0.001). The ARBs cohort had significantly lower rates of newly diagnosed adhesive capsulitis compared to the control cohort at both one year (0.15% vs. 0.55%, p < 0.001) and two years (0.3% vs. 0.78%, p < 0.001). Similar findings were observed for the arthroscopic capsular release/MUA cohort associated with adhesive capsulitis. After adjusting for confounding factors, the lower rates of adhesive capsulitis and arthroscopic capsular release/MUA associated with adhesive capsulitis in the ARBs cohort remained statistically significant (p < 0.001). Patients prescribed ARBs experienced a decrease rate of newly diagnosed adhesive capsulitis, as well as adhesive capsulitis requiring surgical intervention when compared to a control cohort. These findings suggest a potential protective effect of ARBs against the development of adhesive capsulitis. Further investigations are warranted to elucidate the underlying mechanisms and establish a causal relationship.

Blood pressure lowering for kidney transplant recipients: systematic review with network meta-analysis.

Hypertension affects 50-90% of kidney transplant recipients and is associated with cardiovascular disease and graft loss. We aimed to evaluate the comparative benefits and harms of blood pressure lowering agents in people with a functioning kidney transplant. We conducted a systematic review with network meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, and CENTRAL through to October 2023. RCTs evaluating blood pressure lowering agents administered for at least 2 weeks in people with a functioning kidney transplant with and without preexisting hypertension were eligible. Two reviewers independently extracted data. The primary outcome was graft loss. Treatment effects were estimated using random effects network meta-analysis, with treatment effects expressed as an odds ratio (OR) for binary outcomes and mean difference (MD) for continuous outcomes together with their 95% confidence interval (CI). Confidence in the evidence was assessed using GRADE for network meta-analysis. Ninety-four studies (7547 adults) were included. Two studies were conducted in children. No blood pressure-lowering agent reduced the risk of graft loss, withdrawal because of adverse events, death, cardiovascular or kidney outcomes compared with placebo/other drug class. Angiotensin-converting enzyme inhibitors and angiotensin receptor blocker therapy may incur greater odds of hyperkalemia compared with calcium channel blockers [odds ratio (OR) 5.48, 95% confidence interval (CI) 2.47-12.16; and OR 8.67, 95% CI 2.65-28.36; low certainty evidence, respectively). The evidentiary basis for the comparative benefits and safety of blood pressure lowering agents in people with a functioning kidney transplant is limited to guide treatment decision-making.

Comparative effectiveness of sacubitril/valsartan versus angiotensin receptor blockers in patients with heart failure with preserved ejection fraction: A real-world study.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Sacubitril/valsartan (SAC/VAL) or angiotensin receptor blockers (ARBs) are recommended therapy for heart failure with preserved ejection fraction (HFpEF), but little is known about their real-world comparative effectiveness among patients with HFpEF. The objective of this study was to determine the comparative effectiveness of SAC/VAL vs ARBs in preventing HF-related hospitalization or all-cause hospitalization among patients with HFpEF. We conducted a cohort study using IBM MarketScan commercial and Medicare supplemental databases to identify patients aged 18 years or older with a diagnosis of HFpEF and initiation of SAC/VAL (2015-2020) or ARB (2009-2014) therapy. The index date was the date of the first SAC/VAL or ARB prescription fill. After propensity score (PS) matching with a ratio of 1 up to 3, Cox proportional hazards regression was used with robust variance estimators to compare the risks of HF-related hospitalization and all-cause hospitalization between the 2 therapies. Several subgroup and sensitivity analyses were conducted to check the robustness of the main analysis. After PS matching, 2,520 patients (846 receiving SAC/VAL and 1,674 receiving an ARB) were included in the final analyses. After controlling for covariates, there was no difference in the risk of HF-related hospitalization between SAC/VAL and ARB recipients (adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 0.99-1.77). There was also no difference in the risk of all-cause hospitalization between SAC/VAL and ARB recipients (aHR, 1.06; 95% CI, 0.91-1.24). Among individuals with private or Medicare Advantage insurance plans, there was no significant difference in the risk of HF-related hospitalization or all-cause hospitalization between adults with HFpEF who received SAC/VAL and those who received ARB therapy.

Influence of angiotensin receptor and converting enzyme blockers therapy in the respiratory outcome of COVID-19 hospitalized patients

ObjectivesCOVID-19, caused by SARS-CoV-2, has spread around the world since 2019. In severe cases, COVID-19 can lead to hospitalization and death. Systemic arterial hypertension and other comorbidities are associated with serious COVID-19 infection. Literature is unclear whether antihypertensive therapy with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors affect COVID-19 outcomes. We aim to assess whether ACEI/ARB therapy is a risk factor for worse respiratory outcomes related to COVID-19 in hospitalized patients. MethodsRetrospective study enrolling admitted COVID-19-diagnosed patients by RT-PCR at the Hospital Geral de Fortaleza, Brazil, during 2021. Patient medical records, sociodemographic, and clinical data were analyzed. Chest CT images were analyzed using CAD4COVID-CT/Thirona™ software. ResultsA total of 294 patients took part in the study. A cut-off point of 66% of pulmonary involvement was found by ROC curve, with patients having higher risk of death and intubation and lower 60-day survival. Advanced age (RR 1.025, P=0.001) and intubation (RR 16.747, P<0.001) were significantly associated with a higher risk of death. Advanced age (RR 1.023, P=0.001) and the use of noninvasive ventilation (RR 1.548, P=0.037) were associated with a higher risk of intubation. Lung involvement (>66%) increased the risk of death by almost 2.5-fold (RR 2.439, P<0.001) and by more than 2.3-fold the risk of intubation (RR 2.317, P<0.001). ConclusionsAltogether, our findings suggest that ACEI or ARB therapy does not affect the risk of death and disease course during hospitalization.

Influence of angiotensin receptor and converting enzyme blockers therapy in the respiratory outcome of COVID-19 hospitalized patients

ObjectivesCOVID-19, caused by SARS-CoV-2, has spread around the world since 2019. In severe cases, COVID-19 can lead to hospitalization and death. Systemic arterial hypertension and other comorbidities are associated with serious COVID-19 infection. Literature is unclear whether antihypertensive therapy with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors affect COVID-19 outcomes. We aim to assess whether ACEI/ARB therapy is a risk factor for worse respiratory outcomes related to COVID-19 in hospitalized patients. MethodsRetrospective study enrolling admitted COVID-19-diagnosed patients by RT-PCR at the Hospital Geral de Fortaleza, Brazil, during 2021. Patient medical records, sociodemographic, and clinical data were analyzed. Chest CT images were analyzed using CAD4COVID-CT/Thirona™ software. ResultsA total of 294 patients took part in the study. A cut-off point of 66% of pulmonary involvement was found by ROC curve, with patients having higher risk of death and intubation and lower 60-day survival. Advanced age (RR 1.025, P=0.001) and intubation (RR 16.747, P<0.001) were significantly associated with a higher risk of death. Advanced age (RR 1.023, P=0.001) and the use of noninvasive ventilation (RR 1.548, P=0.037) were associated with a higher risk of intubation. Lung involvement (>66%) increased the risk of death by almost 2.5-fold (RR 2.439, P<0.001) and by more than 2.3-fold the risk of intubation (RR 2.317, P<0.001). ConclusionsAltogether, our findings suggest that ACEI or ARB therapy does not affect the risk of death and disease course during hospitalization.

Frailty measured using an electronic frailty index and outcomes in older patients with myocardial infarction

Abstract Background Frailty is common amongst older patients with myocardial infarction and is an independent predictor of poor clinical outcomes. Despite this, frailty is not systematically or objectively measured nor routinely used in risk stratification. The electronic Frailty Index (eFI) is a frailty assessment tool which uses electronic health records to identify and classify frailty and has been shown to correlate well with in-person frailty assessment. However, the performance of the eFI in disease specific populations and its ability to predict individual patient outcomes is unclear. Purpose To assess the relationship between frailty, measured using the eFI, and the management and outcomes of older patients with myocardial infarction. Methods Consecutive patients admitted to hospital in the South East of Scotland between 01/10/2014 and the 01/03/2021 with a primary diagnosis of myocardial infarction were identified using International Classification of Disease (ICD-10) code I21 or I22. Patients under the age of 65 (n= 3,601) and those with no biomarker evidence of myocardial injury were excluded (n=1,301). The provision of guideline recommended therapy, recurrent hospital admission due to myocardial infarction, heart failure or stroke and 12-month all-cause mortality were compared between groups based on eFI classification (fit, mild, moderate or severely frail). Results Of the 3,930 patients (mean age 78 [SD 8] years, 43% female, 83% Caucasian), 2,324 (59%) were classified as frail with 1,421 (36%), 664 (17%), and 239 (6%) classified as mild, moderate and severely frail, respectively. The eFI was measurable in all patients. Patients with any degree of frailty were less likely to receive anti-platelet therapy, ACE inhibitor or angiotensin receptor blocker or beta-blocker therapy or undergo revascularisation with fewer than 1 in 10 patients with severe frailty undergoing inpatient coronary catheterisation (7.5% vs 57% non-frail, P &amp;lt;0.001 for all). Frailty was independently associated with an increased incidence of recurrent myocardial infarction, heart failure or stroke within 12 months with the odds greatest in those with severe frailty (OR 1.93 (95% CI 1.42-2.61%)). The primary outcome of all-cause death at 12-months occurred in 355 (25%), 226 (34%) and 109 (46%) patients with mild, moderate and severe frailty compared with 176 (11%) in non-frail patients (Figure 1). Frailty status was an independent risk factor for all-cause mortality with the risk of death greatest in those with severe frailty (HR 2.64 (95% CI 1.63 – 3.67, p&amp;lt;0.001)). Conclusion The eFI identified patients at increased risk of in-patient death, major adverse cardiovascular events, and all-cause mortality within 12 months following myocardial infarction. Measurement of the eFI from linked healthcare data is feasible and could be used to aide personalised risk stratification and service utilisation in older patients admitted with myocardial infarction.Cumulative incidence plotForest plot with adjusted hazard ratio

FRI203 A Case Of Pseudoadrenal Tumor Mimicking Left Adrenal Pheochromocytoma

Abstract Disclosure: A. Tanabe: None. E. Sugito: None. H. Kajio: None. Approximately 50% of adrenal incidentalomas are non-functional cortical adenomas, and 25% are adrenocortical hormone-secreting adenomas and pheochromocytomas. Adrenocortical carcinomas, and pheochromocytomas which have malignant potential, need to be differentiated and removed even if the tumors are hormonally inactive. In addition to these adrenal origin tumors, anatomic structures and tumors that develop in tissues neighboring the adrenal glands (pseudoadrenal tumors) may be confused with primary adrenal tumors. The larger the tumor, the more difficult it is to determine continuity with the adrenal glands. Herein we report a patient with gastrointestinal stromal tumor (GIST) that mimicked a left adrenal pheochromocytoma. A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. The mass appeared to be in the tip of the lateral limb of the left adrenal gland and was located between the left adrenal gland and the posterior wall of the stomach. The patient had no abnormal findings other than general obesity. The blood pressure was 106/72 mmHg with antihypertensive agents. The plasma corticotropin and cortisol concentrations were normal and suppressed normally after a 1-mg overnight dexamethasone suppression test. The plasma aldosterone concentration and renin activity were increased with angiotensin receptor blocker and diuretic therapy. The 24-h urine fractionated metanephrines levels were at the upper limit of the reference range. Because the tumor showed unenhanced computed tomography (CT) attenuation of 40-50 Hounsfield units, hormonally-inactive adrenocortical carcinoma or pheochromocytoma had to be differentiated. I-123-metaiodobenylguanidine (I-123-MIBG) scintigraphy showed tumor avidity consistent with a pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal CT postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a GIST. Although it has been reported that I-123-MIBG may accumulate in tumors other than neuroendocrine tumors, reports on GISTs are rare. Lessons learned from our case include the importance of clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathologic analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies. Presentation: Friday, June 16, 2023

Effect of SGLT2 inhibitors on the proteinuria reduction in patients with IgA nephropathy.

Recent trials suggest sodium-glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced proteinuria in patients with IgA nephropathy (IgAN). While little was known its efficacy in clinical practice especially in those already received full dose reninangiotensin-aldosterone system (RAAS) inhibitors. A cohort of 93 Chinese patients with biopsy-proven IgAN and persistent proteinuria underwent full supportive therapy, including optimal blood pressure control and full dose angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy. Proteinuria reduction at three and six months after initiating SGLT2i therapy was analyzed. A total of 93 patients were enrolled in this study and 62 of them completed the six-month follow-up. After SGLT2i administration, a significant reduction in proteinuria was observed, with a decrease of 22.9% (p < 0.001) at three months and 27.1% (p < 0.001) at six months. During the six-month follow-up period, a decline of 3.0 mL/min/1.73m2 in estimated glomerular filtration rate (eGFR) (p = 0.012) and an increase of 0.8 g/L in albumin (p = 0.017) were observed. The anti-hypertensive effect of SGLT2i was not significant (p > 0.05). Notably, a consistent antiproteinuric effect of SGLT2i was observed across various settings, including different age groups, baseline levels of proteinuria/eGFR, use of immunosuppressive agents, and the presence of comorbid diabetes and hypertension (all p values >0.05). The proteinuria was significantly reduced after SGLT2i administration in IgAN patients with full dose angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy. Importantly, the antiproteinuric effect of SGLT2i was observed independently of immunosuppressive agent therapy, age, baseline eGFR and proteinuria levels, as well as the history of hypertension and diabetes.

#4057 SUPERIOR PROTEINURIA REDUCTION WITH SPARSENTAN IN IMMUNOGLOBULIN A NEPHROPATHY (IGAN): A PROTECT STUDY INTERIM ANALYSIS

Abstract Background and Aims IgAN is the most common glomerular disease worldwide. Despite optimized standard of care, most patients with IgAN progress to kidney failure within 10-15 years, consequently seriously affecting their quality of life and mortality. Treatments that reduce proteinuria and risk of kidney disease progression are urgently needed for IgAN. Sparsentan is a novel, oral, non-immunosuppressive, single molecule that is a dual endothelin and angiotensin receptor antagonist being investigated for IgAN and focal segmental glomerulosclerosis. The Phase 3 PROTECT study is examining the long-term antiproteinuric and nephroprotective potential and safety of sparsentan compared with an active control, angiotensin receptor blocker (ARB) irbesartan, in adults with IgAN. Reported here are the PROTECT pre-specified interim primary efficacy endpoint and safety outcomes. Method PROTECT is an ongoing, global, Phase 3, multicenter, randomized, double-blind, active controlled study designed to evaluate the efficacy and safety of sparsentan versus the active control irbesartan in adults with IgAN with overt proteinuria despite receiving maximized treatment with an angiotensin converting enzyme inhibitor (ACEi) and/or ARB. The study duration is 270 weeks; the double-blind period is 114 weeks (110 treatment and 4 follow-up) with an open-label extension period up to 156 weeks. Adult patients with biopsy-proven IgAN (excluding IgAN secondary to another condition or IgA vasculitis), urine protein excretion value ≥1.0 g/day, eGFR ≥30 mL/min/1.73m2, systolic/diastolic blood pressure ≤150/≤100 mmHg, and on a stable dose of ACEi and/or ARB therapy for at least 12 weeks prior to screening that is both the patient's maximum tolerated dose and at least one-half of the maximum labeled dose were eligible for inclusion. Patients took their last ACEi and/or ARB dose the day before randomization. Patients were randomized 1:1 to sparsentan or irbesartan (target dose 400 and 300 mg/day, respectively), stratified by screening eGFR and urine protein excretion values. The pre-specified interim primary efficacy endpoint of change from baseline in urine protein/creatinine ratio (UP/C, based on a 24-hour urine sample) at Week 36 was analyzed using a mixed model repeated measures analysis. The safety evaluation included assessment of treatment emergent adverse events. Results A total of 671 patients were screened; 406 patients from clinical sites in 18 countries, including sites in North America, Europe, and Asia Pacific, met eligibility criteria and were enrolled and randomized into PROTECT. Two randomized patients withdrew from the study prior to initiating study treatment. The 404 randomized patients who received study drug were included in the primary analysis population. The mean reduction in UP/C from baseline at 36 weeks was significantly greater in the patients who received sparsentan (-49.8%) versus irbesartan (-15.1%, P&amp;lt;0.0001). Proteinuria reduction consistency across baseline demographic and clinical characteristics and rates of complete and partial remission are reported, as well as sustained proteinuria reduction over time. Safety outcomes related to edema and liver function tests are reported. Overall, sparsentan was generally well-tolerated and comparable to irbesartan. Conclusion The interim results of the PROTECT study show that in adult patients with IgAN and persistent proteinuria above 1 g/day despite being treated with ACEis and/or ARBs, once-daily treatment with sparsentan compared head-to-head with maximum labelled or tolerated irbesartan produced a robust and clinically meaningful reduction in proteinuria. The safety of sparsentan was consistent with previous studies in FSGS and comparable to irbesartan.

Impact of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers on clinical outcomes in hypertensive patients with acute myocardial infarction.

There has been a concern that angiotensin receptor blockers (ARB) may increase myocardial infarction (MI) in hypertensive patients compared with other classes of anti-hypertensive drugs. Angiotensin-converting enzyme inhibitor (ACEI) is recommended as a first-line inhibitor of renin-angiotensin system (RASI) in patients with acute MI (AMI), but ARB is also frequently used to control blood pressure. This study investigated the association of ARB vs. ACEI with the long-term clinical outcomes in hypertensive patients with AMI. Among patients enrolled in the nationwide AMI database of South Korea, the KAMIR-NIH, 4,827 hypertensive patients, who survived the initial attack and were taking ARB or ACEI at discharge, were selected for this study. ARB therapy was associated with higher incidence of 2-year major adverse cardiac events, cardiac death, all-cause death, MI than ACEI therapy in entire cohort. After propensity score-matching, ARB therapy was still associated with higher incidence of 2-year cardiac death (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.20-2.14; P = 0.001), all-cause death (HR, 1.81; 95% CI, 1.44-2.28; P < 0.001), and MI (HR, 1.76; 95% CI, 1.25-2.46; P = 0.001) than the ACEI therapy. It was concluded that ARB therapy at discharge in hypertensive patients with AMI was inferior to ACEI therapy with regard to the incidence of CD, all-cause death, and MI at 2-year. These data suggested that ACEI be a more appropriate RASI than ARB to control BP in hypertensive patients with AMI.

Angiotensin receptor-neprilysin inhibitor delays progression from paroxysmal to persistent atrial fibrillation

Progression from paroxysmal to persistent atrial fibrillation (AF) is linked to adverse clinical outcomes. The present study sought to clarify whether angiotensin receptor-neprilysin inhibitor (ARNI) can delay AF progression. A retrospective cohort study was conducted on consecutive patients with paroxysmal AF admitted at the Second Affiliated Hospital of Nanchang University between January 2017 and January 2022. The risk of AF progression from paroxysmal to persistent was compared between paroxysmal patients treated with ARNI and those who received an angiotensin receptor blocker (ARB). Seven-day Holter monitoring was performed to identify persistent AF. Propensity-score matched analysis was performed to compare the two groups. Cox-regression was used to estimate the hazard ratio (HR) for AF progression events. A total of 1083 patients were screened, and 113 patients in the ARB group and 57 patients in the ARNI group were eligible for analysis. Before propensity-score matching, the ARNI therapy was associated with a lower risk of AF progression than the ARB therapy (HR 0.34; 95% confidence interval [CI] 0.14–0.81; P = 0.015) after a median follow-up of 705 (interquartile range [IQR] 512 to 895) days. Among 170 patients, 47 ARNI-treated patients were successfully matched to 47 ARB-treated patients. After a median follow-up of 724 (541–929) days, compared to ARB, ARNI significantly reduced the risk of AF progression (HR 0.32; 95% CI 0.12–0.88; P = 0.016). ARNI may be superior to ARB in reducing the risk of progression from paroxysmal to persistent AF.

PS-C02-2: THE USE OF HYDROCHLOROTHIAZIDE FOR THE TREATMENT OF HYPERTENSION INCREASES THE CARDIOVASCULAR RISK ACCORDING TO THE CENTRAL HAEMODYNAMIC PARAMETERS

Objective: The chronic use of the diuretic hydrochlorothiazide (Hct) can activate the neurohormonal system, increasing metabolic risk factors it is potentially arrhythmogenic; and can stimulate the escape of aldosterone, even during Angiotensin Receptor Blockers (ARB) treatment. Aldosterone is a hormone with dangerous effects on the cardiovascular system, from arterial/myocardium stiffness to sodium and water retention; also, is involved in the production of reactive oxygen species and endothelial dysfunction. Psoriasis is a systemic disease that exemplifies the intersection of inflammation, immune dysregulation; and accelerating cardiovascular disease. This study aimed to know if the hydrochlorothiazide added to ARB therapy for the treatment of hypertension can produce a deleterious effect on the cardiovascular system similar to psoriasis, and compare the different responses of ARB therapy alone, according to the measuring of the Central Hemodynamic Parameters (CHP). Design &amp; Methods: For this cross-sectional retrospective study data were collected from 994 patients divided into three groups, both sexes. One group of patients with psoriasis female-male (F-M) (65–57) average age (SD) 55.7 (14.7) - 52.1 (12.5). A second group, in the regime of ARB therapy, F-M (237–217) average age (SD), 62.6 (12.8) - 58.5 (13.6). In the third group, during ARB+Hct therapy, F-M (253–165) average age (SD) was 65.2 (11.2) - 61.9 (12.6). For this study were entered anthropomorphic measures, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Heart Rate, CHP, and the Difference between observed values and normal levels of Augmentation Index (Diff-AIx), the surrogate value of arterial stiffness, assessing with a validated device employing the high-fidelity technique of applanation tonometry according to standard methods (SphygmoCor-PVX). All patients had a therapy time length of more than 6 months. The presence in brief phases of atrial fibrillation was in 24hs-Holter monitoring in the 3 groups were registered. Results: Data of SBP, DBP, Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure and Diff-AIx were highest among the groups with ARB+Hct and psoriasis, and ARB therapy with a statistically significant difference, while between the group psoriasis and ARB+Hct was not found a statistically significant. The highest percentage of patients with phases of atrial fibrillation during 24hs-Holter monitoring were found in the group ARB+Hct (13.6%) than ARB therapy (7.5%) with a statistically significant (p &lt; 0.001). Conclusions: The chronic use of Hydrochlorothiazide for hypertension treatment produces deleterious action on hemodynamics and cardiovascular parameters and can increase the development of atrial fibrillation.

Effect of sacubitril/valsartan and ACEI/ARB on glycaemia and the development of diabetes: a systematic review and meta-analysis of randomised controlled trials

BackgroundSacubitril/valsartan and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) therapies were reported to affect glycaemic control and the development of diabetes mellitus (DM), but the findings are inconsistent. We examined the evidence for the effects of sacubitril/valsartan and ACEI/ARB in DM by conducting a meta-analysis.MethodsThe Cochrane Central Register of Controlled Trials (The Cochrane Library), Embase, PubMed, and ClinicalTrials.gov were searched for data from randomised clinical trials (RCTs) that evaluated the efficacy of sacubitril/valsartan and ACEI/ARB in patients, as of May 25, 2022. Patients were grouped by their disease background at baseline. The main outcomes were the number of new-onset DM and hypoglycaemia, elevated glycaemia, inadequate DM control, diabetes treatment, and diabetic complications, from baseline to the end of the trials. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (ROB 2). The quality of the evidence was evaluated according to the Recommendations for Assessment, Development, and Evaluation guidelines. The meta-analysis of the incidence of various outcomes was conducted using fixed or random effects models. The results are expressed as binary risk, 95% confidence interval (CI), and relative risk (RR). The Mantel-Haenszel method and Z test were used to determine the overall results and determine the significance of the RR.ResultsThis study included 31 RCTs and 86,809 subjects. Compared with placebo, sacubitril/valsartan treatment significantly reduced the risk of new-onset DM among all patients (RR = 0.78, 95% CI: 0.64–0.95), patients with heart failure (HF) (RR = 0.24, 95% CI: 0.12–0.48), HF with reduced ejection fraction (HFrEF) (RR = 0.24, 95% CI: 0.12–0.50), and HF with preserved ejection fraction (HFpEF) (RR = 0.54, 95% CI 0.34–0.85). In contrast, sacubitril/valsartan treatment significantly increased the risk of hypoglycaemia among all patients (RR = 1.91, 95% CI: 1.05–3.47), patients with not all-DM (defined as part of the study population having DM at baseline) (RR = 5.71, 95% CI: 2.02–16.21), and patients with HFpEF (RR = 7.06, 95% CI: 2.10–23.76). Compared with ACEI/ARB, sacubitril/valsartan treatment significantly increased the risk of hypoglycaemia among patients with HF (RR 1.85, 95% CI 1.12–3.06, p = 0.02) and HFpEF (RR 3.59, 95% CI 1.51–8.55, p = 0.004). Compared with placebo, ACEI/ARB treatment did significantly reduce the risk of new-onset DM among all patients (RR 0.85, 95% CI 0.77–0.93, p = 0.0007) and patients with not all-HF (defined as part of the study population having HF at baseline) (RR 0.87, 95% CI 0.82–0.93, p<0.0001) and HFpEF (RR 0.60, 95% CI 0.44–0.83, p = 0.002), diabetes complications among patients with non-HF (/not all-DM) (RR 0.87, 95% CI 0.76–0.99, p = 0.04), and subsequent diabetes treatment among patients with new-onset DM (RR 0.70, 95% CI 0.58–0.84, p = 0.0002) and significantly increased the risk of hypoglycaemia among patients with not all-DM (RR 2.06, 95% CI 1.172–3.61, p = 0.01).ConclusionsThe results of our study, especially in reducing glycaemia and new-onset DM, revealed that sacubitril/valsartan had a positive effect on the control of glycaemia and the development of DM. ACEI/ARB also had a beneficial effect but the effect was weaker than that of sacubitril/valsartan. The above effects varied across diseases but the evidence was strongest in patients with HF.Trial registrationCRD42022336311.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation.

Cryoballoon ablation (CBA) is recommended for patients with paroxysmal atrial fibrillation (AF) refractory to antiarrhythmic drugs. However, only 80% of patients benefit from initial CBA. There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) decreases the recurrence of AF postablation, particularly in nonparoxysmal AF undergoing radiofrequency ablation. The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown. We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia (AA) following CBA for paroxysmal AF. To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF. We followed 103 patients (age 60.6 ± 9.1 years, 29% women) with paroxysmal AF undergoing CBA 1-year post procedure. Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring. A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence. After a 1-year follow-up, 19 (18.4%) participants developed recurrence of AA. Use of ACEI or ARB therapy was noted in the study population. Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease. On a multivariate model adjusted for baseline demographics and risk factors for AF, ACEI or ARB therapy did not prevent recurrence of AA following CBA (P = 0.72). Similarly, on Kaplan-Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA (P = 0.2173). In our study population, preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension

Arterial hypertension is associated with an increased incidence of epilepsy. Results from animal studies suggest that angiotensin receptor blocker (ARB) therapy could inhibit epileptic seizures. However, there is a lack of clinical data to support the use of ARB therapy in humans. To assess whether ARB therapy is associated with a decreased incidence of epilepsy in patients with hypertension. This cohort study obtained data from the Disease Analyzer database (IQVIA) on patients aged 18 years or older who had hypertension and at least 1 antihypertensive drug prescription. Patients were treated at 1274 general practices between January 2010 and December 2020 in Germany. Data were available for 1 553 875 patients who had been prescribed at least 1 antihypertensive drug. Patients diagnosed with epilepsy before or up to 3 months after the index date were excluded. A total of 168 612 patients were included in propensity score matching. Patients treated with 1 of 4 antihypertensive drug classes (β-blockers, ARBs, angiotensin-converting enzyme inhibitors, and calcium channel blockers [CCBs]) were matched to each other using propensity scores. The main outcome of the study was the incidence of epilepsy associated with ARB therapy compared with other antihypertensive drug classes. Cox regression models were used to study the association between the incidence of epilepsy and ARBs compared with all other antihypertensive drug classes as a group. The study included a total of 168 612 patients, with 42 153 in each antihypertensive drug class. The mean [SD] age of patients was 62.3 [13.5] years, and 21 667 (51.4%) were women. The incidence of epilepsy within 5 years was lowest among patients treated with ARBs (0.27% at 1 year, 0.63% at 3 years, 0.99% at 5 years) and highest among patients receiving β-blockers and CCBs (0.38% for both β-blockers and CCBs at 1 year; 0.91% for β-blockers and 0.93% for CCBs at 3 years; β-blockers, 1.47%; and CCBs, 1.48% at 5 years). Angiotensin receptor blocker therapy was associated with a significantly decreased incidence of epilepsy (hazard ratio, 0.77; 95% CI, 0.65-0.90) compared with the other drug classes as a group. In this cohort study of patients with hypertension, ARB therapy was associated with a significantly decreased incidence of epilepsy. The findings suggest antihypertensive drugs could be used as a novel approach for preventing epilepsy in patients with arterial hypertension.

S1563 ACE Inhibitor Use Is Associated With Angioectasias on Video Capsule Endoscopy (VCE) in Patients With Iron Deficiency Anemia

Introduction: Small bowel bleeding poses a clinical challenge in patients with vascular lesions. Bleeding recurrence after endoscopic therapy is high and medical therapies have limited efficacy. In those with left ventricular assist devices (LVADs), the use of angiotensin converting enzyme inhibitors (ACEi) has been associated with a reduced rate of gastrointestinal bleeding. Conversely, the antiplatelet effects of ACEi have been described thought due to their effects in decreasing platelet aggregation. Our aim was to determine whether ACEi or angiotensin receptor blocker (ARB) therapy had an impact on the rate of positive VCE small bowel findings in those with iron deficiency anemia (IDA). Methods: Data was collected from consecutive inpatient and outpatient VCE examinations performed between January 1, 2009 to March 1, 2018 at a single U.S. tertiary medical center performed for IDA. VCE studies were excluded in those with incomplete small bowel examinations (9) or technical failure (1). Patient demographics, laboratory values, medication use and endoscopic findings were recorded. VCE findings were based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed using Wilcoxon rank-sum test for continuous variables and Fischer’s exact test for dichotomous variables. Bivariate logistic regression was performed to identify independent factors predictive of positive VCE. Results: Eighty-two VCE were included in the final analysis. Median age was 67.6 (IQR: 57.1-75.5) years and 38 (46.3%) patients were male. Thirty-seven (45.1%) VCE examinations were positive with the most common finding of angiectasia in 21 (55.3%). Risk factors for positive VCE are listed in Table 1. In univariate analysis, ACEi therapy associated with both positive VCE (P=0.014) and the presence of angiectasia (P=0.021), whereas ARB therapy did not associate with positive VCE. ACEi findings remained significant in bivariate analysis after controlling for cardiac and pulmonary comorbidities. Conclusion: In this single center study the presence of ACEi use was associated with small bowel and/or stomach angiectasias on VCE in univariate analysis and when controlled for cardiac and pulmonary risk factors. Further studies are required to determine the mechanistic impact of ACEi on gastrointestinal bleeding risk such as the reduction in von Willebrand factor or factors that affect platelet aggregation. Table 1. - Univariate predictors of positive video capsule endoscopy in iron deficiency anemia Negative VCE (n = 45) Positive VCE (n =37) P-value Age, years, mean (SD) 63.6 (15.8) 68.6 (9.3) 0.303 Male sex, n (%) 21 (46.7) 17 (46) 1 White race, n (%) 22 (48.9) 20 (54.1) 0.223 Active smoking, n (%) 6 (14) 11 (29.7) 0.105 Outpatient location, n (%) 31 (68.9) 21 (56.8) 0.357 Chronic kidney disease, n (%) 10 (22.2) 13 (35.1) 0.224 Chronic liver disease, n (%) 3 (6.7) 4 (10.8) 0.696 Congestive heart failure, n (%) 10 (22.2) 13 (35.1) 0.224 Diabetes mellitus, n (%) 15 (33.3) 15 (40.5) 0.645 Cardiac valvular disease, n (%) 7 (15.6) 6 (16.2) 1 Coronary artery disease, n (%) 14 (31.1) 14 (37.8) 0.641 Cardiac arrhythmia, n (%) 10 (22.2) 18 (48.7) 0.019 Chronic lung disease, n (%) 10 (22.2) 13 (35.1) 0.224 Left ventricular assist device, n (%) 2 (4.4) 2 (5.4) 1 Blood transfusion in the preceding 4 weeks, n (%) 17 (37.8) 16 (43.2) 0.656 Aspirin, n (%) 20 (44.4) 14 (37.8) 0.654 Thienopyridine, n (%) 3 (6.7) 2 (5.4) 1 Coumadin, n (%) 1 (2.2) 5 (13.5) 0.086 SSRI/SNRI, n (%) 7 (15.6) 9 (24.3) 0.404 ACEi 7 (15.6) 15 (40.5) 0.014 ARB 9 (20) 7 (18.9) 1 Hemoglobin, g/dL1 9.9 (1.7) 9.2 (2.3) 0.216 Platelets, 109/L1 225.4 (67.5) 208.6 (84.9) 0.202 BUN, mg/dL1 21.9 (13.1) 26.7 (22) 0.869 Creatinine, mg/dL1 1.3 (0.5) 1.9 (1.5) 0.197 Ferritin, ng/mL,1 128 (259) 39.6 (28.7) 0.966 Percent saturation, %1 14.8 (15.1) 13.7 (15.4) 0.76

Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist.

Overactivation of the renin–angiotensin–aldosterone system (RAAS) has been shown to be pathologic in heart failure and albuminuric chronic kidney disease (CKD), triggering pro-inflammatory and pro-fibrotic cellular pathways. The standard of care in these disease states includes treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Mineralocorticoid receptor antagonists (MRAs) are also a mainstay in the treatment of heart failure with reduced ejection fraction; however, therapy is often limited by treatment-related hyperkalemia. In albuminuric CKD, the risk of hyperkalemia, acute kidney injury (AKI), and hypotension also remains significant. Finerenone is a novel non-steroidal MRA that may obviate some of these concerns and have therapeutic potential in additional patient populations. Finerenone was developed using the chemical structure of a dihydropyridine channel blocker but optimized to create a bulky MRA without any activity at the L-type calcium channel. It has several novel cellular mechanisms that may account for its ability to reduce cardiac hypertrophy and proteinuria more efficiently than an equinatriuretic dose of a steroidal MRA, while retaining anti-inflammatory and anti-fibrotic properties. Finerenone also has a lower rate of treatment-related hyperkalemia and AKI than steroidal MRAs with a smaller effect on systolic blood pressure, greatly expanding its therapeutic utility. The recently published FIGARO-DKD and FIDELIO-DKD trials demonstrate that treatment with finerenone in patients with type II diabetes and albuminuric CKD results in improved cardiovascular outcomes and a lower risk of CKD progression. Patients enrolled in these studies were already on maximally tolerated ACE inhibitor or angiotensin receptor blocker therapy. Trials investigating finerenone’s therapeutic effect in patients with heart failure with preserved ejection fraction (HFpEF) and non-diabetic CKD, as well sodium–glucose cotransporter 2 (SGLT2) and finerenone combination therapy in patients with diabetic nephropathy, are ongoing.

Neonatal presentation of Loeys-Dietz syndrome: two case reports and review of the literature

BackgroundLoeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, especially aortic dilatations and arterial tortuosity, craniofacial and skeletal features, joint laxity or contractures, skin abnormalities, hypotonia and motor delay. Its diagnosis is established by the identification of a pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3 genes. In newborns and toddlers, vascular complications such as aneurism rupture, aortic dissection, and intracerebral incidents, can occur already in the weeks of life. To avoid these events, it is crucial to precociously identify this condition and to start an apunderwent a surgical procedurepropriate treatment which, depending on the severity of the vascular involvement, might be medical or surgical.Case presentationWe report two cases of Loeys-Dietz syndrome precociously diagnosed. The first describes a male, born at 38 + 1 weeks of gestation, with hypotonia, joint hypermobility, arachnodactyly, and fingers joint contractures, as well as senile appearance and facial dysmorphisms. In the suspect of a connective tissue disorder, an echocardiography was performed and revealed an aortic root dilatation of 13 mm (Z score + 3). A trio based Whole Exome Sequencing found a novel de novo variant in the TGFBR2 gene. Despite the onset of a low-dose angiotensin receptor blocker therapy, the aneurysm progressed. The second case describes a female, born at 41 + 3 weeks of gestation. During the neonatal examination a cleft palate was noticed, as well as minor dysmorphisms. Since the family history was suspicious for connective tissue disorders, a genetic panel was performed and identified a pathogenetic variant in TGFB3 gene. In this case, the echocardiography revealed no abnormalities.ConclusionsIn addition to our cases, we identified 14 subjects with neonatal LDS in the medical literature. All of them had aortic involvement. Skeletal and face abnormalities, including eyes and palate malformations, were also highly frequent. Overall, 10 subjects required medical therapy to avoid aneurysm progression, and 8 patients underwent surgical procedures.Benefits of an early diagnosis of LDS are various and imply a potential modification of the natural history of the disease with early interventions on its complications.