Use Of Angiotensin Receptor Blockers Research Articles

ODP190 Efficacy of Esaxerenone on Hypertensive Patients with Type 2 Diabetes or Those with Impaired Glucose Tolerance

Abstract Patients with diabetes may develop mineralocorticoid receptor (MR) related hypertension due to abnormal activation of MR, thusMR blocker (MRB) is used for the treatment of hypertensionin patients with diabetes. Although theselective MRB esaxerenone (Esax)approved for hypertension, the effectiveness of Esax in daily clinical practice has not provenin hypertensive patients with type 2 diabetes (T2D) or those withimpaired glucose tolerance (IGT). The aim of this study is to clarifythe efficacy of Esax in these patients. In this retrospective study, patientswho initiated Esax from May 2019 to February 2020 and thosewho initiated amlodipine (Amlo) were screened. After excluding patients with a history of hypersensitivity to these drugs, K > 5. 0 mEq/L at the baseline and severe renal dysfunction (eGFR < 30 mL/min/1.73m 2), and patients receiving potassium preparations, 35 and 70 patients were enrolled in the Esax and Amlo group, respectively. After propensity score matching with the parameters including gender, age, body mass index (BMI), concomitant use of angiotensin receptor blocker, systolic blood pressure (SBP), diastolic blood pressure (DBP), K, AST, ALT, TG and eGFR, finally each 24 cases were analyzed. Primary endpoints were changes (Δ) in SBP and DBP from the baseline to 6 months after the initiation of the drugs. Secondary endpoints comprised changes in liver enzymes and those in lipid metabolism markers. Unpaired t-test was used for statistical analysis. The dose of Esax and Amlo were 2.2±0.5 mg and 4.1±1.2 mg at the baseline, and 3.4±1.3 mg and 5.3±1.2 mg at 6 months, respectively. SBP was more decreased in the Esax group compared with the Amlo group (ΔSBP: -27± 20 mmHg vs -11± 14 mmHg, p<0. 05). DBP was not significantly different between the two groups (ΔDBP: -11± 10 mmHg vs -9± 14 mmHg). In the Esax group, ALT and TG were significantly decreased (ΔAST: -7.3 ± 11.5 U/L vs +0.9 ± 9.5 U/L, p<0. 05,ΔTG: -14.3 ± 51. 0 mg/dL vs +33.5 ± 59.4 mg/dL, p<0. 05), and HDL-C significantlyincreased (ΔHDL: +1.8 ± 6.1 mg/dL vs -3.8 ± 4.8 mg/dL, p<0. 05). Severeadverse events were not observed in any subjects. These results suggest the efficacy of Esax for controlling blood pressure as well as the plausible benefit in liver disease and lipid metabolism in hypertensive patients with T2D or IGT. Presentation: No date and time listed

The Impact of Different Antihypertensive Drugs on Cardiovascular Risk in Isolated Systolic Hypertension with Type 2 Diabetes Patients.

Angiotensin receptor blockers (ARB), angiotensin converting enzyme inhibitor (ACEI), calcium channel blocker (CCB) and thiazide diuretics (TD) are common antihypertensive drugs for diabetes patients with hypertension. The purpose of this study was to compare the cardiovascular risks of these drugs in patients with isolated systolic hypertension (ISH) and type 2 diabetes mellitus (T2DM). We used Action to Control Cardiovascular Risk in Diabetes trial data to explore the relationship between antihypertensive drugs and cardiovascular risks in ISH with T2DM patients by performing propensity score matching, Kaplan-Meier survival analyses and Cox proportional regression. The cumulative incidence rates of primary outcomes (PO, including cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke) in the ARB use group were significantly lower than those without (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.34-0.83; p = 0.006). However, for ACEI, CCB and TD, they were negligible (ACEI: p = 0.209; CCB: p = 0.245; TD: p = 0.438). ARB decreased cardiovascular mortality (CM) in PO rather than non-fatal myocardial infarction (NMI) and non-fatal stroke (NST) (CM: HR 0.32; 95%CI 0.18-0.90; p = 0.004; NMI: p = 0.692; NST: p = 0.933). ARB may alleviate the cardiovascular risks in ISH with T2DM patients, but ACEI, CCB, and TD did not.

Updates on Pharmacologic Management of Microvascular Angina.

Microvascular angina (MVA), historically called cardiac syndrome X, refers to angina with nonobstructive coronary artery disease. This female-predominant cardiovascular disorder adds considerable health-related costs due to repeated diagnostic angiography and frequent hospital admissions. Despite the high prevalence of this diagnosis in patients undergoing coronary angiography, it is still a therapeutic challenge for cardiologists. Unlike obstructive coronary artery disease, with multiple evidence-based therapies and management guidelines, little is known regarding the management of MVA. During the last decade, many therapeutic interventions have been suggested for the treatment of MVA. However, there is a lack of summarization tab and update of current knowledge about pharmacologic management of MVA, mostly due to unclear pathophysiology. In this article, we have reviewed the underlying mechanisms of MVA and the outcomes of various medications in patients with this disease. Contrary to vasospastic angina in which normal angiogram is observed as well, nitrates are not effective in the treatment of MVA. Beta-blockers and calcium channel blockers have the strongest evidence of improving the symptoms. Moreover, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, estrogen, and novel antianginal drugs has had promising outcomes. Investigations are still ongoing for vitamin D, omega-3, incretins, and n-acetyl cysteine, which have resulted in beneficial initial outcomes. We believe that the employment of the available results and results of the future large-scale trials into cardiac care guidelines would help reduce the global cost of cardiac care tremendously.

Angiotensin receptor blockade is associated with increased risk of giant cell arteritis.

Angiotensin II is implicated in GCA pathology. We examined whether the use of angiotensin receptor blockers (ARBs) is associated with GCA risk compared with angiotensin-converting enzyme inhibitors (ACEis) or other antihypertensives. We performed a matched cohort study including adults who were initiators of antihypertensives in UK primary care data between 1995 and 2019. Treatment-naïve individuals without prior GCA or PMR were categorized into three groups-ARB initiators, ACEi initiators, or other antihypertensive initiators (beta-blockers, calcium channel blockers, diuretics or alpha-adrenoceptor blockers)-and followed for up to 5 years. Incident GCA was defined using validated Read codes, with age of onset ≥50 years and two or more glucocorticoid prescriptions. Inverse probability-weighted Cox models were used to model outcome risk, adjusting for lifestyle parameters, comorbidities and comedications. Among >1 million new starters of antihypertensives (81 780 ARBs, 422 940 ACEis and 873 066 other antihypertensives), the incidence rate of GCA per 10 000 patient-years was 2.73 (95% CI 2.12, 3.50) in the ARB group, 1.76 (95% CI 1.25, 2.39) in the ACEi group and 1.90 (95% CI 1.37, 2.56) in the other antihypertensives group. The hazard of GCA was higher in ARB initiators [hazard ratio (HR) 1.55; 95% CI 1.16, 2.06] than initiators of ACEis, but similar between initiators of other antihypertensives and ACEis (HR 1.08; 95% CI 0.87, 1.35). Initiation of ARBs is associated with a higher risk of GCA compared with ACEis or other antihypertensives. Mechanistic studies of angiotensin receptor biology will provide further clarity for our findings.

Factors associated to renin-angiotensin-aldosterone system inhibitors discontinuation or down-titration due to hyperkalaemia in patients with chronic cardiovascular conditions

Abstract Background/Introduction The renin-angiotensin-aldosterone system inhibitors (RAASI) are one of the keystones of the medical treatment in chronic cardiovascular disorders and have shown improvements in clinical outcomes in many clinical trials. Hyperkalaemia is a well-defined non-desirable effect of RAASI that occasionally forces to interrupt these medications. That enforced RAASI discontinuation or down-titration due to hyperkalaemia may have adverse prognostic consequences. Purpose Describe the demographical, clinical and pharmacological variables associated to a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia among individuals with chronic cardiovascular conditions. Methods We used data from more than 375,000 individuals 55 years of age or older, included in the population-based healthcare database of a public Institute of Health between 2015 and 2017. We included participants with at least one relevant condition: chronic heart failure, chronic kidney disease, diabetes mellitus, ischemic heart disease or hypertension. They had to be under RAASI treatment as of January 1st, 2016, and with evidence of at least one episode of hyperkalaemia (serum potassium >5.0 mmol/L) during 2016. Then, were classified in one of the two following profiles: RAASI treatment discontinuation or down-titration versus RAASI treatment unchanged or up-titrated. For the statistical analysis, we used logistic regression to calculate the multivariable-adjusted odds ratios of each study variable, comparing RAASI discontinuation or down-titration group to RAASI treatment unchanged or up-titrated controls (reference group). Results In the multivariable-adjusted model, the risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia was significantly associated with the use of RAASI, very high comorbidity index, potassium derangements (both hypokalaemia and hyperkalaemia), prior hospitalizations and prior emergency visits. Among RAASI treatments, the use of Angiotensin receptor blockers (OR 2.518, 95% CI 2.317–2.735) and Angiotensin-converting enzyme inhibitors (OR 2.341, 95% CI 2.149–2.549) were associated with a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia than Aldosterone inhibitors (1.428, 95% CI 1.285–1.584). Conclusion These results suggest that vulnerable populations such as those with very high comorbidity index, potassium derangements or prior emergency visits or hospitalizations have a higher risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia. A more careful and exhaustive management of RAASI should be advised in those patients. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Josep Comin-Colet has received speaker fees from Vifor Pharma.

Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure

Albuminuria, routinely assessed as spot urine albumin-to-creatinine ratio (UACR), indicates structural damage of the glomerular filtration barrier and is associated with poor kidney and cardiovascular outcomes. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce UACR in patients with type 2 diabetes, but its use in patients with heart failure (HF) is less well studied. To analyze the association of empagliflozin with study outcomes across baseline levels of albuminuria and change in albuminuria in patients with HF across a wide range of ejection fraction levels. This post hoc analysis included all patients with HF from the EMPEROR-Pooled analysis using combined individual patient data from the international multicenter randomized double-blind parallel-group, placebo-controlled EMPEROR-Reduced and EMPEROR-Preserved trials. Participants in the original trials were excluded from this analysis if they were missing baseline UACR data. EMPEROR-Preserved was conducted from March 27, 2017, to April 26, 2021, and EMPEROR-Reduced was conducted from April 6, 2017, to May 28, 2020. Data were analyzed from January to June 2022. Randomization to empagliflozin or placebo. New-onset macroalbuminuria and regression to normoalbuminuria and microalbuminuria. A total of 9673 patients were included (mean [SD] age, 69.9 [10.4] years; 3551 [36.7%] female and 6122 [63.3%] male). Of these, 5552 patients had normoalbuminuria (UACR <30 mg/g) and 1025 had macroalbuminuria (UACR >300 mg/g). Compared with normoalbuminuria, macroalbuminuria was associated with younger age, races other than White, obesity, male sex, site region other than Europe, higher levels of N-terminal pro-hormone brain natriuretic peptide and high-sensitivity troponin T, higher blood pressure, higher New York Heart Association class, greater HF duration, more frequent previous HF hospitalizations, diabetes, hypertension, lower eGFR, and less frequent use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and mineralocorticoid receptor antagonists. An increase in events was observed in individuals with higher UACR levels. The association of empagliflozin with cardiovascular mortality or HF hospitalization was consistent across UACR categories (hazard ratio [HR], 0.80; 95% CI, 0.69-0.92 for normoalbuminuria; HR, 0.74; 95% CI, 0.63-0.86 for microalbuminuria; HR, 0.78; 95% CI, 0.63-0.98 for macroalbuminuria; interaction P trend = .71). Treatment with empagliflozin was associated with lower incidence of new macroalbuminuria (HR, 0.81; 95% CI, 0.70-0.94; P = .005) and an increase in rate of remission to sustained normoalbuminuria or microalbuminuria (HR, 1.31; 95% CI, 1.07-1.59; P = .009) but not with a reduction in UACR in the overall population; however, UACR was reduced in patients with diabetes, who had higher UACR levels than patients without diabetes (geometric mean for diabetes at baseline, 0.91; 95% CI, 0.85-0.98 and for no diabetes at baseline, 1.08; 95% CI, 1.01-1.16; interaction P = .008). In this post hoc analysis of a randomized clinical trial, compared with placebo, empagliflozin was associated with reduced HF hospitalizations or cardiovascular death irrespective of albuminuria levels at baseline, reduced progression to macroalbuminuria, and reversion of macroalbuminuria. ClinicalTrials.gov Identifiers: NCT03057977 and NCT03057951.

Drugs acting on the renin–angiotensin–aldosterone system (RAAS) and deaths of COVID-19 patients: a systematic review and meta-analysis of observational studies

BackgroundAngiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are two of the most commonly used antihypertensive drugs acting on the renin–angiotensin–aldosterone system (RAAS). Previous research has shown that RAAS inhibitors increase the expression of angiotensin-converting enzyme, a cellular receptor for the severe acute respiratory syndrome coronavirus 2, raising concerns that the use of ACEi and ARBs in hypertensive patients may increase COVID-19 patient mortality. Therefore, the main aim of the current study was to find out the role of drugs acting on RAAS, particularly ACEi/ARBs in the deaths of COVID-19 patients.ResultsIn total, 68 studies were found to be appropriate, reporting a total of 128,078 subjects. The odds ratio was found to be 1.14 [0.95, 1.36], which indicates the non-significant association of ACEi/ARBs with mortality of COVID-19 patients. Further, the association of individual ACEi/ARBs with mortality of COVID-19 patients was also found non-significant. The sensitivity analysis results have shown no significant effect of outliers on the outcome.ConclusionsBased on available evidence, ACEi/ARB were not significantly associated with deaths of COVID-19 patients.

An overview of the effects of combination therapy with a renin-angiotensin system blocker plus a calcium channel blocker on glucose homeostasis in non-diabetic hypertensive patients

Arterial hypertension (AH) is a major cardiovascular risk factor and often coexists with insulin resistance. Insulin resistance impairs glucose homeostasis and has been associated with the development of new-onset type 2 diabetes mellitus (T2D). Overactivity of renin-angiotensin system (RAS) mediated by angiotensin II adversely affects glucose homeostasis. The blockade of RAS with the use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) has been associated with beneficial effects on glucose metabolism. On the other hand, calcium channel blockers (CCBs) have been reported to exert a metabolic neutral effect. By contrast, the use of diuretics and beta-blockers has been shown to have an overall negative effect on glucose metabolism. Current ESH/ESC treatment guidelines recommend the use of fixed single-pill combinations of RAS blockers with either CCBs or thiazide/thiazide-like diuretics in hypertensive patients with grade 1 AH and high cardiovascular risk, or greater. Nonetheless, considering the patient’s medical history and comorbidities, antihypertensive treatment should be carefully tailored. To this, hypertensive patients at risk of developing new-onset T2D, with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), should be preferentially treated with either monotherapy or combined treatment using agents which do not affect or worsen glucose homeostasis.

The histological spectrum of ARB-induced gastritis.

Olmesartan, an angiotensin receptor blocker (ARB) used for hypertension management, is known to cause a sprue-like enteropathy in a subset of patients. Rare cases of gastritis occurring with ARB use have also been reported, but the histological features of ARB-induced gastritis and the response to drug cessation have not been examined in a dedicated case-series. Cases of suspected ARB-induced gastritis were identified from the pathology archives of four institutions. Haematoxylin and eosin (H&E) slides from gastric biopsies were reviewed. Fifteen patients (14 female, one male) were identified. The most common presenting symptoms were diarrhoea (10) and weight loss (six). Gastric biopsies commonly showed a full-thickness active chronic gastritis with surface epithelial injury involving the antrum and body. Glandular atrophy, intra-epithelial lymphocytosis and/or subepithelial collagen thickening were also present in some cases. Duodenal involvement, including villous atrophy, intra-epithelial lymphocytosis and/or collagenous sprue, was identified in 11 of 13 cases with concurrent duodenal biopsies. Following drug cessation, symptomatic improvement occurred in all 11 cases for which follow-up data were available. Histological resolution occurred in five of eight cases with follow-up gastric biopsies, with improvement seen in the remaining three biopsies. ARB-induced gastritis typically presents as active chronic gastritis, frequently with associated surface epithelial injury. Glandular atrophy, intra-epithelial lymphocytosis and/or subepithelial collagen thickening may also be present. These gastric changes can be seen without associated duodenal injury in rare cases, and they should alert the pathologist to the possibility of ARB-induced injury. Drug cessation results in marked symptomatic and histological improvement.

Angiotensin receptor blocker use is associated with upregulation of the memory-protective angiotensin type 4 receptor (AT4R) in the postmortem brains of individuals without cognitive impairment.

The reported primary dementia-protective benefits of angiotensin II type 1 receptor (AT1R) blockers (ARB) are believed, at least in part, to arise from systemic effects on blood pressure. However, there is a specific and independently regulated brain renin-angiotensin system (RAS). Brain RAS acts mainly through three receptor subtypes; AT1R, AT2R, and AT4R. The AT1R promotes inflammation and mitochondrial reactive oxygen species generation. AT2R increases nitric oxide. AT4R is essential for dopamine and acetylcholine release. It is unknown whether ARB use is associated with changes in the brain RAS. Here, we compared the impact of treatment with ARB on not cognitively impaired individuals and individuals with Alzheimer's dementia using postmortem frontal-cortex samples of age- and sex-matched participants (70-90years old, n = 30 in each group). We show that ARB use is associated with higher brain AT4R, lower oxidative stress, and amyloid-β burden in NCI participants. In AD, ARB use was associated with lower brain AT1R but had no impact on inflammation, oxidative stress, or amyloid-β burden. Our results may suggest a potential role for AT4R in the salutary effects for ARB on the brains of not cognitively impaired older adults.

Effects of RAS inhibitors on all-site cancers and mortality in the Hong Kong diabetes surveillance database (2002-2019).

SummaryBackgroundCancer is replacing cardiovascular-disease as a leading cause of death in type 2 diabetes (T2D). The association of RAS-inhibitors (RASi) and cancer, including differences between angiotensin-converting-enzyme-inhibitor (ACEi) and angiotensin-receptor-blocker (ARBs) as well as their associations independent of blood pressure lowering, remains inconclusive in T2D.MethodsWe conducted a cohort study with new-user design in 253,491 patients in the Hong-Kong-Diabetes-Surveillance-Database (HKDSD) in 2002-2019. We evaluated the associations of time-varying RASi use (ACEi and ARBs) with all-site cancer, diabetes-related cancers, and cancer-specific mortality including comparison with new-users of calcium-channel-blockers (CCBs) as an active-comparator group.FindingsOf 253,491, 133,730 (52.8%) were new-RASi and 119,761 (47.2%) were non-RASi users with a median follow-up period of 6.3 (interquartile ragne: 3.4-9.2) years (1,678,719 patient-years). After propensity-score weighting and adjustment for time-varying covariables, RASi use was associated with lower risk of all-site cancer (HR=0.76, 95%CI: 0.74-0.79), diabetes-related cancer (HR=0.79, 95%CI: 0.75-0.84), cancer-specific mortality (HR=0.50, 95%CI: 0.47-0.53), and diabetes-related cancer mortality (HR=0.49, 95%CI: 0.45-0.54) versus non-RASi. Amongst RASi users, ARBs use was associated with lower risk of cancer-specific mortality versus ACEi (HR=0.77, 95%CI: 0.66-0.91). Use of RASi was associated with an estimated-prevention of 2.6 (95%CI: 2.3-3.0) all-site cancer per-1000-person-years and 2.2 (95%CI: 2.0-2.5) cancer-related mortality per-1000-person-years. Lower risk of cancer-specific mortality was similarly observed in new-RASi compared with new-CCBs users.InterpretationRASi use was independently associated with lower cancer risk in T2D with stronger associations in users of ARBs than ACEi. The benefits of RASi in patients with diabetes might go beyond cardiovascular-renal protection if confirmed by other real-world studies and trials.FundingDr. Aimin Yang was supported by a CUHK Impact-Research-Fellowship Scheme.

The effect of ACE inhibitors and ARBs on outcomes in hospitalized patients with COVID-19.

Background Contradictory opinions exist regarding the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with hypertension, which is the most common comorbidity associated with COVID-19. Herein, the effects of ACEIs and ARBs on outcomes of COVID-19 patients were evaluated.MethodsIn this cross-sectional study, the outcomes of COVID-19 patients were compared between patients who received pretreatment ACEIs or ARBs and those who did not.ResultsThe incidence of moderate and severe forms of COVID-19 was significantly higher in patients taking ACEI/ARB drugs (P-value = 0.012). Also, patients taking ACEI/ARB drugs (P-value = 0.034), patients with hypertension (P-value = 0.011), and patients with dyslipidemia (P-value = 0.011) experienced more severe forms of COVID-19. There was an association between increased length of hospital stay and dyslipidemia (P-value = 0.033) and the use of ACEI/ARB drugs (P-value = 0.041), while no correlation was found between other parameters in univariate linear regression analysis as well as multivariate linear regression. There was an association between increased mortality of patients with increasing age (P-value < 0.001), BMI greater than 30 kg/m2 (P-value = 0.02), asthma (P-value = 0.003), and dyslipidemia (P-value = 0.045).ConclusionsACEI/ARB drugs put COVID-19 patients at high risk for moderate to severe forms of COVID-19 and higher length of hospital stay. Although, it is notable that these drugs did not significantly affect specific adverse outcomes of COVID-19, such as the need for admission to the intensive care unit (ICU), length of ICU stay, ventilation, and mortality.

Potential for repurposing oral hypertension/diabetes drugs to decrease asthma risk in obesity

Objective Risk for asthma in the overweight/obese may be mediated by adiponectin and peroxisome proliferator activated receptor pathways and may be reduced by the use of oral drugs impacting these pathways, such as angiotensin converting enzyme inhibitors (ACE-I), thiazolidinediones (TZD), and angiotensin receptor blockers (ARB). Our study objective was to determine whether ACE-I, TZD, and/or ARB use in overweight/obese adults with diabetes mellitus and/or hypertension is associated with a lower risk for incident asthma. Methods Using an existing cohort of American veterans, we performed a longitudinal data analysis over 15 years. Exposure was defined by the prescription pickup of ACE-I, TZD, and/or ARB for at least 4 weeks. The outcome, time until new-onset of clinician-diagnosed asthma, was studied using survival analysis. The propensity scoring method controlled for treatment selection bias. Results 2.83 million eligible veterans, including 77,278 with incident asthma, were studied. As compared to those unexposed, the use of ACE-I alone, TZD alone, or their combinations were each associated with decreased risk for incident asthma (hazard ratios of 0.88, 0.74, and 0.20, respectively; p < 0.001 for all analyses in the fully adjusted statistical models). TZD lowered the risk among racial/ethnic minority subjects more than among White participants (p < 0.001). On the other hand, ARB use alone or in combination with TZD was associated with a higher risk for incident asthma. Conclusions Use of ACE-I and/or TZD was associated with a lower risk for incident asthma in overweight/obese patients with diabetes mellitus and/or hypertension.

A Rare Case of Synchronous Severe Duodenal Ulcers and Acute Colitis in Sartan-Induced Enteropathy: A Case Report and Review of Literature

Sartan induced sprue-like enteropathy (SIE) was initially reported as a side effect of chronic Olmesartan use in 2012 and is characterized by chronic diarrhoea and weight loss. The diagnosis is often difficult and requires ruling out of other causes of enteropathy including infectious gastroenteritis, autoimmune enteropathy and celiac disease. A 51 – year – old Caucasian male was admitted to our hospital because of chronic non-bloody diarrhoea associated with severe acute renal failure and electrolyte imbalances. His medical history was only positive for hypertension for which he was on Olmesartan Medoxomil and Lacidipine, both of which were discontinued due to hypotension at admittance. Stool cultures and search for C. Difficile toxin resulted negative, whilst a Colonscopy showed endoscopic and histological signs of aspecific acute colitis. After having responded to i.v. hydration with normalization of the renal function the patient was discharged home with the same medications he was on before admittance. His diarrhoea relapsed and he was readmitted shortly afterwards with acute renal failure and electrolyte imbalances; the anti-hypertensive medications were again discontinued. After having excluded all other causes of diarrohea, including celiac disease and HIV, Sartan – induced enteropathy (SIE) was suspected and then confirmed with an esophagogastroduodenoscopy which revealed a severe erosive duodenitis with multiple duodenal ulcers. The patient again responded to i.v. hydration with normalization of the renal function and Olmesartan was held also at discharge without further relapse of the symptoms. SIE is a rare cause of chronic diarrhoea, weight loss and possible severe renal failure. It could affect the whole gastrointestinal tract and in cases of unexplained non-bloody diarrhea, suspecting SIE is fundamental and should be considered in the differential diagnosis. Discontinuation of the drug is generally sufficient for symptom resolution: in suspected cases with a positive medical history for chronic angiotensin receptor blocker (ARB) use, stopping the drug ex-juvantibus should be undertaken. Further research on the immunopathological mechanisms and how to recognize patients at higher risk of developing this condition is deemed necessary.

Effect of Renin-Angiotensin-Aldosterone System Inhibitors on the Rupture Risk Among Hypertensive Patients With Intracranial Aneurysms.

Mounting experimental evidence supports the concept that the RAAS (renin-angiotensin-aldosterone system) is involved in the pathogenesis of intracranial aneurysm rupture. However, whether RAAS inhibitors could reduce the rupture risk of intracranial aneurysms remains unclear. We performed a chart review of a multicenter, prospectively maintained database of 3044 hypertensive patients with intracranial aneurysms from 20 medical centers in China. The patients were separated into ruptured and unruptured groups. Univariable and multivariable logistical regression analyses were performed to determine the association between the use of RAAS inhibitors and the rupture risk. Sensitivity analyses and subgroup analyses were performed to verify the robustness of the results. In multivariable analyses, female sex, passive smoking, uncontrolled, or unmonitored hypertension, use of over 2 antihypertensive medications, RAAS inhibitors use, antihyperglycemic agents use, hyperlipidemia, ischemic stroke, and aneurysmal location were independently associated with the rupture risk. The use of RAAS inhibitors was significantly associated with a reduced rupture risk compared with the use of non-RAAS inhibitors (odds ratio, 0.490 [95% CI, 0.402-0.597]; P=0.000). Compared with the use of non-RAAS inhibitors, the use of ACE (angiotensin-converting enzyme) inhibitors (odds ratio, 0.559 [95% CI, 0.442-0.709]; P=0.000) and use of ARBs (angiotensin receptor blockers; odds ratio, 0.414 [95% CI, 0.315-0.542]; P=0.000) were both significantly associated with a reduced rupture risk. The negative association of the rupture risk with RAAS inhibitors was consistent across 3 analyzed data and the predefined subgroups (including controlled hypertension). The use of RAAS inhibitors was significantly associated with a decreased rupture risk independent of blood pressure control among hypertensive patients with intracranial aneurysms.

Angiotensin Receptor Blockers in the Management of Hypertension: A Real-World Perspective and Current Recommendations.

Hypertension represents a major common cardiovascular risk factor. Optimal control of high blood pressure levels is recommended to reduce the global burden of hypertensive-mediated organ damage and cardiovascular (CV) events. Among the first-line drugs recommended in international guidelines, renin-angiotensin-aldosterone system antagonists [angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs)] have long represented a rational, effective, and safe anti-hypertensive pharmacological strategy. In fact, current US and European guidelines recommend ACEi and ARBs as a suitable first choice for hypertension treatment together with calcium channel blockers (CCBs) and thiazide diuretics. Different studies have demonstrated that ARBs and ACEi exert a comparable effect in lowering blood pressure levels. However, ARBs are characterized by better pharmacological tolerability. Most importantly, the clinical evidence supports a relevant protective role of ARBs toward the CV and renal damage development, as well as the occurrence of major adverse CV events, in hypertensive patients. Moreover, a neutral metabolic effect has been reported upon ARBs administration, in contrast to other antihypertensive agents, such as beta-blockers and diuretics. These properties highlight the use of ARBs as an excellent pharmacological strategy to manage hypertension and its dangerous consequences. The present review article summarizes the available evidence regarding the beneficial effects and current recommendations of ARBs in hypertension. The specific properties performed by these agents in various clinical subsets are discussed, also including an overview of their implications for the current COVID-19 pandemic.

142-LB: Cognitive Screening among Older Adults with Diabetes

Background: Diabetes affects approximately 24.4% of older adults in the United States and increases the risk of cognitive dysfunction and future dementia. Patients with cognitive dysfunction may find it harder to manage their diabetes and have more complications such as hypoglycemia. Yearly cognitive screening is recommended for all older adults with diabetes but may not be widely conducted. Methods: We performed cognitive screening with the Mini-Cog test for a subset of patients with diabetes seen in Endocrine Clinics in one large healthcare system in 2020-21. We used a retrospective chart review to compare patient screening results between Endocrine (Endo) , Geriatric (Geri) and multidisciplinary Endo-Geriatric practices (Geri-Endo) . We used Chi-square tests to examine differences between clinic cohorts and a multivariate logistic regression to predict risk of cognitive dysfunction. We adjusted for age, ethnicity, sex, type of diabetes, Sulfonylurea (SU) use, ACE inhibitors (ACEI) / Angiotensin Receptor Blocker (ARB) use, smoking history, statin use, and BMI. Findings: Among 198 patients screened (Endo=80, Geri=32, Geri-Endo=86) , those seen in Geri-endo (40.7%) and Geri (31.3%) were more likely to have lower Mini-COG scores (lower scores suggest worse cognition) as compared to those in Endo (6.3%) (p&amp;lt;.0001) . Patients in Endo and Geri-Endo had longer duration of diabetes, were more likely to use insulin and had higher incidence of documented hypoglycemia. Higher age &amp;gt; 75 years (p=0.0105) , previous CV events (p=0.0006) and BMI &amp;lt;30 (p=0.0115) were significantly associated with lower Mini-COG scores. Conclusion: Our study shows that cognitive screening can help identify older adults at risk for dementia in diabetes clinic. Patients with older age, previous CV events and lower BMI may be at higher risk for cognitive dysfunction. Older adults should be screened yearly for cognition as part of routine diabetes care. Disclosure D. Gupta: None. H. Wilhalme: None. G. Sauder: None. T. Moin: None. Funding NIH National Center for Advancing Translational Science (NCATS) , UCLA CTSI (UL1TR001881)

An Analysis of Vascular Access Thrombosis Events From the Proactive IV irOn Therapy in hemodiALysis Patients Trial

IntroductionTreatment of anemia in dialysis patients has been associated with increased risk of vascular access thrombosis (VAT). Proactive IV irOn Therapy in hemodiALysis Patients (PIVOTAL) was a clinical trial of proactive compared with reactive i.v. iron therapy in patients requiring hemodialysis. We analyzed the trial data to determine whether randomized treatment arm, alongside other clinical and laboratory variables, independently associated with VAT.MethodsIn PIVOTAL, 2141 adult patients were randomized. The type of vascular access (arteriovenous fistula [AVF], arteriovenous graft [AVG], or central venous catheter [CVC]) was recorded at baseline and every month after randomization. The associations between clinical and laboratory data and first VAT were evaluated in a multivariate analysis.ResultsA total of 480 (22.4%) participants experienced VAT in a median of 2.1 years of follow-up. In multivariable analyses, treatment arm (proactive vs. reactive) was not an independent predictor of VAT (hazard ratio [HR] 1.13, P = 0.18). Diabetic kidney disease (HR 1.45, P < 0.001), AVG use (HR 2.29, P < 0.001), digoxin use (HR 2.48, P < 0.001), diuretic use (HR 1.25, P = 0.02), female sex (HR 1.33, P = 0.002), and previous/current smoker (HR 1.47, P = 0.004) were independently associated with a higher risk of VAT. Angiotensin receptor blocker (ARB) use (HR 0.66, P = 0.01) was independently associated with a lower risk of VAT.ConclusionIn PIVOTAL, VAT occurred in nearly 1 quarter of participants in a median of just >2 years. In this post hoc analysis, randomization to proactive i.v. iron treatment arms did not increase the risk of VAT.

Preventive role of angiotensin receptor blockers on the recurrent AF in hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: None. Background The structural remodeling makes important contributions to the AF substrate. The formation of connective tissue in response to injury (cardiac fibrosis) is a hallmark of arrhythmogenic structural remodeling. The atrial fibrosis decrease can be helpful in preventing the onset and recurrence of AF. Inflammatory mechanisms may form a basis for new agents more likely to prevent recurrent episodes of AF. The renin-angiotensin-aldosterone system plays an important role in the pathogenesis of AF in correlation with the inflammatory process. The aim of this study is to access the role of long-term treatment by sartans on the regression of left heart remodeling and the frequency of AF recurrence after successful cardioversion in hypertensive patients. Methods We have follow up 119 hypertensive patients with paroxysmal / persistent AF after successful cardioversion during 10-12 months. All patients divided into two groups: group A (62 patients) treated by Losartan daily dose 50 -100 mg or Valsartan daily dose 160mg for 10-12 months. As a control group B of similar 57 patients received standard antihypertensive therapy, but without taking sartans. Both groups were received supporting antiarrhythmic therapy with Аmiodarone (200-300 mg daily). The patients underwent clinical examination, echocardiography, ECG Holter monitoring and determination of plasma levels of inflammatory and fibrosis markers - high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and profibrotic cytokine - transforming growth factor beta (TGF-β1) by ELIZA. Statistical analysis was performed by SPSS-16. Results The obtained results have shown that it was no significant differences of the antihypertensive effect in both patients groups. But the obtained data of structural remodeling regression in A and B groups were differed significantly. Thus, in the A group decrease in LVTDV, TMZHP and LVEDD and an improvement in left ventricular diastolic function were revealed, on compared to the B group which showed only a tendency to improve these indicators. Moreover, in group A, there was a significant decrease in the concentration of inflammation and fibrosis markers compared with the control group. We obtained a positive correlation between hsCRP and LAD (r=0.58, p&amp;lt;0.001) and LVEDD (r=0.51, p&amp;lt;0.001), between TGF-β1 and LAD (r=0.55, p&amp;lt;0.001), LVEDD (r=0.59, p&amp;lt;0.001) and number of AF episodes (r=0.489, p&amp;lt;0.001.). The negative correlation was found between hsCRP and TGF-β1 (r=-0.36, p&amp;lt;0.01). It was revealed that in a group recurrence of AF was less than in B group (6.8% vs 10%). Conclusion These results confirmed that the use of angiotensin receptor blockers improves some cardiac remodeling parameters, decreases the frequency of AF recurrence in hypertensive patients with successful cardioversion and contributes to prevent AF episodes.

MO339: The Effect of Pre-Admission Angiotensin-Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) Use on the Incidence of Acute Kidney Injury and Mortality in Patients With Septic Shock

Abstract BACKGROUND AND AIMS In the early stages of sepsis, the renin–angiotensin–aldosteron system (RAAS) is activated despite adequate volume resuscitation. Overactivity of RAAS might contribute to an inferior outcome in patients with severe sepsis, therefore modulation of RAAS could be beneficial in preventing organ failure and reducing mortality. Recommendation to discontinue angiotensin convertase enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) for the prevention of acute kidney injury (AKI) in these patients is currently controversial. In this retrospective cohort study, we aimed to study the potential effect of pre-hospital ACEI or ARB use on the incidence of AKI and mortality in patients admitted to the intensive care unit (ICU) with septic shock. METHOD A total of 536 patients admitted to a single ICU for septic shock during a 5-year period were selected for inclusion in the study. Pre-admission ACEi/ARB exposure was extracted from the admission documents. Propensity score matching based on age, gender, diabetes, hypertension and cardiovascular disease (CVD) was used to control for baseline differences between ACEi/ARB treated and control patients. Stages of AKI were defined according to the KDIGO criteria, using the first available creatinine level as a baseline. Since ACEi/ARB therapy was discontinued after admission, AKI was only considered within the first 3 days of admission. The incidence of AKI stages was compared between treated and control patients. In addition, multivariate logistic regression models were used to assess the association between ACEi/ARB use and mortality in the ICU. RESULTS A total of 241 treated and 274 control patients were identified after matching. The mean age was 71 ± 9 years, 42% were female, the prevalence of diabetes and CVD were 36% and 72%, respectively. As expected, baseline GFR on admission in the treated group was lower compared with control: 37 mL/min versus 49 mL/min; P = .005. The incidence of AKI was similar in both groups: 25 versus 28%; P = .593. The somewhat higher proportion of patients with AKI stage 1 in the treated group (6.6% versus 3.3%) did not reach statistical significance (P = .170). This most likely reflects the glomerular hemodynamic effect of RAS inhibition. The incidence of stage 2 and 3 AKI was comparable in treated (19.1%) and control groups (25.4%, P = .233). Patient survival was similar in both groups: 63.1% versus 58.6%; P = .461. In the whole cohort of 536 patients, only baseline GFR remained an independent predictor of AKI stage 2 or 3 (OR 1.6 for 10 mL/min decline; P &amp;lt; .001) in the multivariate analysis. AKI stage 2 and 3 (OR 3.324; P &amp;lt; .001) and cardiovascular disease (OR 2.288; P = 0.003) were independent predictors of mortality. ACEi/ARB exposure was not associated with patient outcome in our cohort. CONCLUSION In this retrospective cohort study, we confirmed that pre-admission ACEi/ARB use was not associated with a higher risk of AKI in patients with septic shock admitted to the ICU. Our results suggest that ACEi/ARB treatment could be continued until the patient's blood pressure allows in early stages of sepsis.