Angiotensin Receptor Blockers Research Articles

Sacubitril-Valsartan in Patients Requiring Hemodialysis.

Randomized clinical trials have shown that sacubitril-valsartan reduces the risks of mortality and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF), but patients with kidney failure requiring dialysis were excluded. To investigate the comparative effectiveness of sacubitril-valsartan vs angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs or ARBs) in patients with HFrEF requiring hemodialysis. This retrospective, 1:1 propensity score-matched comparative effectiveness study included patients who were 18 years or older with HFrEF, enrolled in Medicare Parts A, B, and D, and survived at least 90 days receiving in-center hemodialysis from July 8, 2015, to December 31, 2020. Patients were excluded for less than 180 days of continuous Medicare Parts A, B, and D primary payer coverage or prior dispensing of sacubitril-valsartan. Data analysis was conducted from September 23, 2023, to June 25, 2024. New use of sacubitril-valsartan vs new or continued use of ACEIs or ARBs. The associations between initiation of sacubitril-valsartan therapy and all-cause mortality, cardiovascular mortality, all-cause hospitalization, and HF hospitalization were assessed using Cox proportional hazards regression models in a propensity score-matched sample. Participants included 1:1 matched pairs of 1434 sacubitril-valsartan users and 1434 ACEI or ARB users (mean [SD] age, 64 [13] years). Of the 2868 matched participants, 996 (65%) were male; 987 (34%) were Black or African American and 1677 (58%) were White; and median dialysis vintage was 3.8 (IQR, 1.8-6.3) years. The median follow-up was 0.9 (IQR, 0.4-1.7) years. Sacubitril-valsartan (vs ACEI or ARB) therapy was associated with a reduction in all-cause mortality (hazard ratio [HR], 0.82 [95% CI, 0.73-0.92]) and all-cause hospitalization (HR, 0.86 [95% CI, 0.79-0.93]) but not cardiovascular mortality (HR, 1.01 [95% CI, 0.86-1.19]) or HF hospitalization (HR, 0.91 [95% CI, 0.82-1.02]). There was a decrease in hyperkalemia (HR, 0.71 [95% CI, 0.62-0.81]) and no difference in hypotension (HR, 0.99 [95% CI, 0.83-1.19]). Only 195 participants (14%) ever received the maximum combination dose of sacubitril (97 mg twice daily) and valsartan (103 mg twice daily). In this comparative effectiveness study of patients with HFrEF requiring hemodialysis, sacubitril-valsartan therapy was associated with beneficial effects in all-cause mortality and all-cause hospitalization.

Characteristics, treatment and prognosis of patients with chronic heart failure according to ejection fraction. Results of an Ecuadorian registry.

In Ecuador, there are few data about the clinical behaviour of heart failure (HF). This study aims to analyse the clinical characteristics, treatment and prognosis according to the current classification based on left ventricular ejection fraction (EF). A retrospective observational study was carried out in patients with chronic HF from the 'Los Ceibos' registry during the period January 2017-December 2022. Patients were classified into HF with preserved EF (HFpEF) [EF ≥ 50%], HF with mildly reduced EF (HFmrEF) [EF:41-49%], and HF with reduced (HFrEF) [EF ≤ 40%]. The patients were followed up for a mean time of 2.28 (IQR 1.25-3.49) years. A total of 711 patients were included, 333 (46.8%) with HFrEF, 109 patients (15.3%) with HFmrEF and 269 patients (37.8%) with HFpEF. The average age was 69.8 ± 13.1 years, 31.4% were women. The main comorbidity was arterial hypertension (92.7%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were used in 74.5%, beta-blockers in 82.3%, and mineralocorticoid receptor antagonists in 51.3%. 58.3% of patients with HFrEF received three drugs of the so-called foundational quadruple therapy. A lower all-cause (24.5%) and cardiovascular mortality rate (11,2%) was observed in the HFpEF group compared to HFmrEF (47.4% and 25,7%) and HFrEF (45.3% and 25,8%), p < 0.001. In the 'Los Ceibos' registry, a higher prevalence of HFrEF was observed. The main comorbidity was HTN. Half of the patients with HFrEF received three drugs of the foundational therapy. At four years of follow-up, lower all-cause and cardiovascular mortality rate was observed in the HFpEF group.

A pharmacovigilance study assessing risk of angioedema with angiotensin receptor blockers using the US FDA Adverse Event Reporting System

ABSTRACT Background Angiotensin receptor blockers (ARBs) are widely used for treating hypertension and heart failure. Angioedema has been reported as a controversial adverse effect of ARBs and the evidence on individual ARB risks is limited. This study aimed to assess signals of angioedema with different ARBs using the US FDA Adverse Event Reporting System (AERS) database. Research design and methods Reports of angioedema from 2004 to 2024 in AERS with an ARB as the primary suspect were extracted using Medical Dictionary for Regulatory Activities queries. Disproportionality analyses including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker were conducted to identify safety signals for individual ARBs. Results A total of 3,683 unique reports met the selection criteria. Irbesartan and losartan generated signals in all statistical measures, followed by telmisartan and candesartan in some measures. Valsartan had the highest report count. Most reports reported hospitalization, prolonged hospitalization or life-threatening outcomes consequent to angioedema. Conclusion This pharmacovigilance study using AERS highlights potential higher risks of angioedema with losartan and irbesartan compared to other ARBs, warranting validation through prospective epidemiological studies to characterize individual ARB safety profiles.

Pharmacogenetics of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in cardiovascular diseases

Cardiovascular diseases (CVDs) have a high mortality rate, and despite the several available therapeutic targets, non-response to antihypertensives remains a common problem. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are important classes of drugs recommended as first-line therapy for several CVDs. However, response to ACEIs and ARBs varies among treated patients. Pharmacogenomics assesses how an individual's genetic characteristics affect their likely response to drug therapy. Currently, numerous studies suggest that genetic polymorphisms may contribute to variability in drug response. Moreover, further studies evaluating gene-gene interactions within signaling pathways in response to antihypertensives might help to unravel potential genetic predictors for antihypertensive response. This review summarizes the pharmacogenetic data for ACEIs and ARBs in patients with CVD, and discusses the potential pharmacogenetics of these classes of antihypertensives in clinical practice. However, replication studies in different populations are needed. In addition, studies that evaluate gene-gene interactions that share signaling pathways in the response to antihypertensive drugs might facilitate the discovery of genetic predictors for antihypertensive response.

Long-term exposure to antihypertensive drugs and the risk of cancer occurrence: evidence from a large population-based study.

Available data on the association between antihypertensive drugs and cancer are characterized by a few years follow-up. Our aim has been to evaluate the association between long-term exposure to antihypertensive drugs and the risk of cancer occurrence. Using the healthcare utilization databases of the Lombardy region (Italy), individuals aged 40-85 years who had no previous history of cancer and were newly dispensed with at least one antihypertensive drug from the major drug classes between 2009 and 2011 were followed from the first drug dispensation to December 31, 2020. Data were analyzed according to the first drug used and the intention to treat principle, but also via an "as treated" approach, that is, by considering changes of and exposure to drugs during follow-up. The association between the duration of exposure to each drug class and the risk of cancer occurrence was evaluated using the adjusted Cox regression models. The study cohort included 338 910 new drug users (median age, 59 years; 49.5% males). During a median follow-up of 10.2 years, 36 556 cancers occurred. There was no consistent significant association between the risk of cancer occurrence and angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, or thiazides. A progressive, weak increase in cancer occurrence was associated with progressive exposure to calcium channel blockers and, limited to long-term exposure, to beta-blockers. A modest progressive increase in risk was observed also for thiazide-like and loop diuretics in the as treated, although not in the intention to treat approach. Long-term evaluation of exposure to antihypertensive drugs did not show consistent associations between thiazides, angiotensin-receptor blockers, or angiotensin-converting-enzyme inhibitors and the risk of cancer occurrence. A weak association was observed between cancer and the duration of exposure to calcium channel blockers and beta-blockers.

The effects of antihypertensive drugs on glucose metabolism.

Abnormal glucose metabolism is a common disease of the endocrine system. The effects of drugs on glucose metabolism have been reported frequently in recent years, and since abnormal glucose metabolism increases the risk of microvascular and macrovascular complications, metabolic disorders, and infection, clinicians need to pay close attention to these effects. A variety of common drugs can affect glucose metabolism and have different mechanisms of action. Hypertension is a common chronic cardiovascular disease that requires long-term medication. Studies have shown that various antihypertensive drugs also have an impact on glucose metabolism. Among them, α-receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers can improve insulin resistance, while β-receptor blockers, thiazides and loop diuretics can impair glucose metabolism. The aim of this review was to discuss the mechanisms underlying the effects of various antihypertensive drugs on glucose metabolism in order to provide reference information for rational clinical drug use.

Postprandial hypotension is more common than orthostatic hypotension in older adults with dementia with lewy bodies: a cross-sectional study

Cardiovascular autonomic dysfunction is one of the supportive clinical features in dementia with Lewy bodies (DLB). This study aimed to investigate the frequency of postural and postprandial hypotension in people with DLB. The study group comprised 125 patients with DLB (76 females; mean age 78.4 ± 7.1 years) and 122 controls (88 females; mean age 74.4 ± 6.9 years). Postprandial blood pressure changes were assessed by ambulatory 24-hour blood pressure monitorization. Postural blood pressure changes were assessed via the head-up tilt table test. The frequency of postprandial hypotension (PPH) and orthostatic hypotension (OH) was higher in patients with DLB compared to controls (89.4% vs 51.7%; p < 0.001, and 45.5% vs 27.9%; p = 0.004, respectively) whereas the frequency of supine hypertension (SH), and orthostatic hypertension (OHT) was similar. However, SH in non-hypertensive participants was higher in DLB patients than in controls (48.9%, 25.7%; p = 0.035). PPH and OH were independently associated with a diagnosis of DLB (odds ratio [OR]:10.26 confidence interval [CI]%95 3.02–34.82; p < 0.001, and OR:2.22 CI%95 1.2–4.12; p = 0.012, respectively) after adjustment for age, number of medications, use of anti-psychotics drugs, angiotensin receptor blockers, and beta blockers. In conclusion, the study demonstrated that PPH was the most common finding of cardiovascular autonomic dysfunction, followed by OH and SH in older patients with DLB. Given the potential complications of postural blood pressure changes and PPH in such patients, cardiovascular autonomic dysfunction should be evaluated in patients with DLB.

HEART FAILURE AND CHRONIC KIDNEY DISEASE: PROGNOSIS AND THERAPEUTIC AND SURGICAL OPTIONS.

Heart failure (HF) and chronic kidney disease (CKD) are frequently interrelated conditions that significantly affect patients' quality of life and survival. Both conditions share common risk factors, such as diabetes mellitus and hypertension, and can exacerbate each other. HF can lead to deterioration in renal function due to reduced renal blood flow and activation of neurohormonal mechanisms. Conversely, CKD can worsen HF by causing volume overload and disrupting electrolyte balance. Managing these conditions requires an integrated approach that considers the complex interactions between the cardiovascular and renal systems. Objective: To analyze the therapeutic and surgical options available for treating heart failure in patients with chronic kidney disease and evaluate their impact on patients' prognosis. Methodology: The study followed the PRISMA checklist and involved a systematic search of PubMed, Scielo, and Web of Science databases. Keywords included "heart failure," "chronic kidney disease," "therapeutic options," "surgical options," and "prognosis." Inclusion criteria were articles published in the last 10 years, studies addressing both HF and CKD, and research providing data on therapeutic or surgical interventions. Studies focusing solely on one condition, articles outside the review's scope, and non-peer-reviewed research were excluded. Results: The results indicated that an integrated treatment approach, including risk factor management, specific pharmacotherapy, and surgical interventions, can significantly improve patient prognosis. Therapeutic options, such as ACE inhibitors and angiotensin receptor blockers, have shown benefits in reducing symptoms and disease progression. Surgical interventions, such as coronary revascularization and kidney transplantation, were also associated with improvements in clinical outcomes. Conclusion: Emphasized that a combined and multidisciplinary approach is essential to optimize treatment and quality of life for these patients, highlighting the importance of personalized and integrated strategies for therapeutic success.

ACE Inhibitor and Angiotensin Receptor Blocker Use During Pregnancy: Data From the ESC Registry Of Pregnancy and Cardiac Disease (ROPAC)

Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester due to the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester and about the impact of stopping just before pregnancy. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and evaluates the impact on perinatal outcomes. The Registry of Pregnancy and Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. ACE-I (n=35) and/or ARB (n=8) were used in 42 (0.7%) of the 5739 ROPAC pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p=0.021), had chronic hypertension (31% vs 6%, p<0.001), or a left ventricular ejection fraction <40% (33% vs 4%, p<0.001). In the multivariable analysis, ACE-I use during the first trimester was associated with an increased risk of congenital anomaly (OR 3.2; 95% CI 1.0-9.6). Therefore, ACE-Is should be avoided during pregnancy, also in the first trimester, due to a higher risk of congenital anomalies. However, there is no need to stop long before pregnancy. Preconception counseling is crucial to discuss the potential risks of these medications, to evaluate the clinical condition and, if possible, change or stop the medication.

Study of thermally induced interactions between active substances from the sartans class and various excipients

AbstractSartans, also known as angiotensin receptor blockers, comprise a category of antihypertensive medications designed to inhibit the actions of angiotensin II (Ang II) in the body, ultimately reducing blood pressure levels. This class of compounds is derived from 2-(1-benzyl-1H-imidazol-5-yl)-acetic acid, with its origin characterized by an imidazole core that underwent various substitutions at specific positions within the heterocyclic nucleus. We investigated the behavior of Losartan, Valsartan and Irbesartan and their compatibility with various excipients used in pharmaceutical tablet formulations by FTIR spectroscopic studies, thermal behavior by thermogravimetry and differential scanning calorimetry. The aim of the study was to determine the excipients to be used in pharmaceutical formulations containing drugs from the class of sartans as active ingredients. Our study concludes by recommending precautionary measures in elaborating new solid formulations containing lactose in the case of Losartan.

A retrospective analysis of e-prescriptions for non-communicable diseases on a telehealth platform in Malaysia

BackgroundThe management of non-communicable diseases (NCDs) has benefited from telehealth services. As these services which include teleconsultation services and e-prescriptions are relatively new in Malaysia, the data generated provide an unprecedented opportunity to study medication use patterns for the management of NCDs in the country. We analyze e-prescriptions from a local telehealth service to identify medication use patterns and potential areas to optimize medication use in relation to clinical practice guidelines.MethodsA cross sectional observational study was conducted by retrieving e-prescription records retrospectively from a telehealth service. 739,482 records from January 2019 to December 2021 were extracted using a designated data collection form. Data cleaning, standardization and data analysis were performed using Python version 3.11. The diagnoses were classified according to the International Classification of Disease 10 (ICD-10), while medications were classified using the Anatomical Therapeutic Chemical (ATC) system. Diagnoses, frequency of use for medication classes and individual medications were analyzed and compared to clinical practice guidelines.ResultsThe top five NCD diagnoses utilized by the service were hypertension (37.7%), diabetes mellitus (25.1%), ischemic heart disease (24.3%), asthma (14.4%), and dyslipidemia (11.7%). Medications were prescribed mostly in accordance with guideline recommendations. However, angiotensin receptor blockers (ARBs) were significantly more frequently prescribed compared to angiotensin converting enzyme inhibitors (ACEIs). Several medication classes appeared underutilized, including ACEIs in hypertensive patients with diabetes or ischemic heart disease, sodium glucose cotransporter 2 inhibitors in diabetic patients with ischemic heart disease, and metformin in patients with diabetes.ConclusionsTelehealth services are currently being utilized for the management of NCDs. Medication use for the management of NCDs through these services are mostly in accordance with guideline recommendations, but there exist areas that would warrant further investigation to ensure optimal clinical and economic outcomes are achieved.

Predictors of prolonged supratherapeutic serum lithium concentrations: a retrospective chart review

Introduction The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup suggests hemodialysis in severe lithium poisoning if specific criteria are met. One criterion is if the expected time to obtain a lithium concentration <1.0 mEq/L with optimal management is >36 h. There are a lack of data regarding which patient characteristics are associated with the rate at which patients achieve a lithium concentration <1.0 mEq/L. Methods We conducted a retrospective chart review analyzing hospital electronic medical records. Inclusion criteria consisted of a lithium concentration >1.2 mEq/L during hospitalization. We excluded patients who received extracorporeal treatment before 36 h elapsed from time of initial lithium concentration >1.2 mEq/L. The primary analysis consisted of a Cox regression and a secondary analysis evaluated the nomogram method described by Buckley and colleagues for predicting prolonged supratherapeutic lithium concentration. Results One hundred and one patients were included in the study. The median time to reach a lithium concentration <1.0 mEq/L was 42.5 h (IQR: 33.8–51.1). Older patients, patients taking a thiazide, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, patients with a higher initial lithium concentration, and patients with higher sodium concentrations achieved a lithium concentration <1 mEq/L at a slower rate. For the nomogram analysis, sensitivity (61.5%) and specificity (54.5%) were moderate, the positive predictive value (16.7%) was poor, and the negative predictive value (90.6%) was excellent. Discussion The results from our primary analysis suggest that identifying higher serum sodium concentration and use of certain antihypertensives that decrease glomerular filtration rate as predictors of an increased time to reach a therapeutic lithium concentration may help identify patients who meet the Extracorporeal Treatments in Poisoning criteria for hemodialysis. The nomogram method performed similarly to prior validation studies. Conclusions In this retrospective chart review of patients with supratherapeutic lithium concentrations, we identified several risk factors for prolonged supratherapeutic lithium concentrations.

Efficacy and safety of dapagliflozin in children with kidney disease: real-world data

BackgroundDapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown results in slowing estimated glomerular filtration rate (eGFR) decline and reducing proteinuria in adult patients with chronic kidney disease. This retrospective study examines dapagliflozin’s effects in 22 children with kidney disease and proteinuria.MethodsChildren with a median age of 15.6 years were treated with dapagliflozin for > 3 months between July 2022 and December 2023. All children had been treated with either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least 1 month before starting dapagliflozin.ResultsThe most common kidney disease diagnoses in this study included Alport syndrome (n = 7) and medication-resistant nephrotic syndrome or focal segmental glomerulosclerosis (n = 7). After 6.1 months of treatment, dapagliflozin treatment did not result in significant changes in eGFR or proteinuria. However, at the latest follow-up, a statistically significant decrease in eGFR was noted (65.5 compared to the baseline 71.1 mL/min/1.73 m2, P = 0.003). Proteinuria remained stable between baseline and the last follow-up (final spot urine protein/creatinine ratio (uPCR) 0.7 vs. baseline uPCR 0.6 mg/mg, P = 0.489). In the subgroup analysis of children treated for > 8 months, the eGFR decline post-treatment changed from − 0.5 to − 0.2 ml/min/1.73 m2 per month (P = 0.634). Only two children discontinued dapagliflozin due to suspected adverse events.ConclusionsDapagliflozin has not been associated with serious side effects. Further prospective clinical trials are needed to confirm the efficacy and safety of dapagliflozin in children with kidney disease.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Evaluation of antihypertensive drug-induced changes in mandibular bone using fractal analysis

ObjectivesThe aim was to evaluate changes in trabecular and cortical mandibular bone caused by antihypertensive (AHT) drugs through fractal analysis. MethodsThis retrospective study included 230 patients who were taking AHT medication and had no conditions affecting bone metabolism other than hypertension. A control group of 230 healthy, sex-matched individuals was also included. Patients were divided into subgroups according to AHT drugs: thiazide diuretics (TDs), beta-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and a combination of drugs. The fractal dimension (FD) was calculated bilaterally in 5 regions of interest (ROI 1 – ROI 5) including 4 trabecular regions and 1 cortical region using Image J software. ResultsMean FD values were significantly higher in all ROIs for the study group compared to the control group (P<0.001). FDs were significantlty higher for BB, ACEI, ARB, CCB, and combined subgroups compared to controls in ROIs 1, 2, and 4; for ACEI and CCB subgroups compared to controls in ROI 3; and for TD, BB, ACEI, ARB, CCB, and combined subgroups compared to controls in ROI 5 (P<0.001). ConclusionAHTs may increase FD values of the trabecular and cortical structures. Assessment of the effects of AHT drugs is essential for predicting the prognosis for bone healing after tooth extraction, osseointegration after implant surgery or other surgical procedures.

Management of Hypertension in Patients with Type 2 Diabetes Mellitus: Indian Guideline 2024 by Association of Physicians of India and Indian College of Physicians.

In India and the Southeast Asian population, hypertension and type 2 diabetes mellitus (T2DM) are the leading lifestyle-related diseases, responsible for a majority burden of morbidity and mortality. Multiple population-spanning studies have revealed the staggering prevalence of both diseases in India, and the prevalence of both will only increase further due to factors such as an aging population, rapid urbanization, increased obesity, and sedentary lifestyles. More than 50 percent of hypertensive patients in India are also diagnosed with T2DM, and a detailed management protocol for the same is required, especially when a major portion of the disease is managed at the primary care level. The Association of Physicians of India (API) guidelines for the management of hypertension in patients with T2DM have been formulated based on consultation with leading physicians, cardiologists, diabetologists, and endocrinologists of India and Southeast Asia, keeping in mind the challenges faced by the patients in these countries and the appropriate management protocols that will be beneficial. While standard office-based blood pressure (BP) measurement forms the cornerstone of hypertension diagnosis and demands a uniform methodology to be followed, home blood pressure monitoring (HBPM) is recommended for long-term follow-up with validated devices. Ambulatory blood pressure monitoring (ABPM) offers comprehensive insights crucial for cardiovascular (CV) risk stratification. The complications of diabetic hypertension can span from increased CV risk, heart failure (HF), and renal dysfunction, and nonpharmacological and pharmacological management should be aimed toward not only control of the BP values but also protecting the end organs. While nonpharmacological measures include a focus on nutrition and diet, they also focus on approaches to weight loss, including a novel section covering the benefits of yoga. The guideline also focuses on a novel section of factors influencing CV risk, especially in the Indian population. For the pharmacological management, the guidelines address each of the categories of antihypertensive drugs, emphasizing the significance of combination therapies in the management of diabetic hypertension. In line with leading global guidelines for the management of hypertension in T2DM, for diabetic patients who often struggle with BP management and carry a high CV risk, the recommended dual combination antihypertensive therapy is particularly crucial and should be considered as first-line management therapy. While angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) play a highly beneficial role in the management of diabetic hypertension, a combination of ACEi or ARB with dihydropyridine calcium channel blockers (DHP-CCBs) is recommended to reduce the risk of complications and enhance patient adherence. To achieve the target of effective BP control and end-organ protection, it is beneficial and recommended to include newer CCBs (e.g., cilnidipine) in the management protocol in combination with ACEi/ARBs. Combination therapy including ARBs and DHP-CCBs should be preferred over β-blockers and thiazides. Among the CCBs, cilnidipine, a novel molecule, is a more effective and safer option for diabetic hypertensive patients in India. β-blockers should be used if there is a history of myocardial infarction (MI), HF, coronary artery disease (CAD), or stable angina along with the initial hypertensive regimen. The guideline also focuses on the novel reno- and cardioprotective molecules such as finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) and their benefits in the management of diabetic hypertension.

Current Practices and Emerging Therapies to Optimize Heart Failure Management in Cardiac Sarcoidosis: A Systematic Review.

Cardiac sarcoidosis (CS) is a distinctive manifestation of sarcoidosis, a multisystemic inflammatory disorder that is characterized by non-necrotizing granulomas. CS can lead to arrhythmias, heart failure (HF), and sudden cardiac death. The diagnosis of CS involves imaging in the form of a two-dimensional echocardiogram, cardiac magnetic resonance imaging (MRI), an 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan, and an endomyocardial biopsy. Treatment of CS entails corticosteroids, immunosuppressive agents, monoclonal antibodies, and, in advanced cases, heart transplantation (HTx). This systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, focusing on HF in sarcoidosis patients. Eligibility criteria include recent (2019-2024) research papers on sarcoidosis-induced heart failure, excluding other causes. The databases searched were PubMed, Google Scholar, and ScienceDirect. From 36,755 initial articles, 2,060 remained after filtering, and 17 were selected for quality assessment. Based on quality assessment, 11 studies were included in the final review. In CS, a variety of treatment strategies can be implemented. Corticosteroids are the first-line therapeutic options, and in the majority of cases, they are very successful in controlling the disease progression. Immunosuppressive agents like methotrexate and azathioprine are used to avoid long-term steroid use. Both corticosteroids and immunosuppressives act by reducing inflammation and preventing myocardial scarring. Biological agents like infliximab and adalimumab prevent disease progression by targeting specific inflammatory pathways and are used in refractory cases. Regular HF management drugs like angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), sodium-glucose transport protein 2 (SGLT2) inhibitors, beta-blockers, and diuretics help in optimizing cardiac function. In severe cases, a left ventricular assist device (LVAD) may be required. The ultimate treatment for end-stage CS is HTx, which has to be supplemented with a strong, individualized regimen of glucocorticoids and immunosuppressives to avoid graft rejection and to control sarcoidosis. Due to a lack of standard protocols for management and limited knowledge about CS, the ideal treatment of HF is still a matter of debate. Hence, further research and clinical trials need to be performed to optimize patient outcomes.

Impact of Different Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blocker Resumption Timing on Post Acute Kidney Injury Outcomes

IntroductionEvidence suggests a survival benefit from resuming ACEI/ARB post-AKI compared to non-use, yet the optimal timing and its impact on outcomes are unclear. The risks of earlier resumption, such as recurrent AKI or hyperkalemia, remain unexplored. MethodUsing multi-institutional electronic health records, we analyzed the relationship between three ACEI/ARB resumption timelines post-AKI (prior to discharge, 0-3 months, and 4-6 months post-discharge) and outcomes including all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), dialysis initiation or end-stage renal disease (ESRD), severe hyperkalemia, and recurrent AKI with hospitalization. Cox proportional models estimated hazard ratios for outcomes across different resumption timings, following a target trial design. ResultsAmong 5,392 AKI survivors resuming ACEI/ARB within 6 months post-AKI, earlier resumption was associated with lower mortality, MACCE, MACCE-related mortality, new dialysis initiation or ESRD (P < 0.001 in trend tests), without increased risks of severe hyperkalemia and re-AKI admissions. Early resumption have a lower mortality compared to 4-6 months post-discharge (before discharge, HR 0.88, 95% CI: 0.83-0.93; 0-3 months, HR 0.89, 95% CI: 0.85 - 0.94). Subgroup analysis showed a lower mortality hazard ratio from earlier resumption among AKI survivors with prior ACEI/ARB comorbidities indications (P < 0.001 in trend tests; before discharge, HR 0.85, 95% CI: 0.80-0.90; 0-3 months, HR 0.88, 95% CI: 0.83 -0.93). ConclusionsOur cohort demonstrates lower risks for mortality, cardiovascular events, and ESRD with early ACEI/ARB resumption, without heightened risks of severe hyperkalemia or rehospitalization for AKI. Early resumption should be considered for patients with indications for ACEI/ARB.

Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs.

Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR). This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate). Receiver operating characteristic curves for steroid-probability scores and the ARR were examined with and without interfering medications. Impacts of individual medications on plasma aldosterone, 18-oxocortisol, 18-hydroxycortisol, steroid-probability scores, renin, and ARRs were examined by multivariable and paired analyses in patients with and without PA. Receiver operating characteristic curves indicated a significant impact of interfering antihypertensive medications on the diagnostic performance of the ARR and minimal impact on steroid-probability scores. Mineralocorticoid receptor antagonists increased plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol in patients without PA and resulted in false-positive test results for steroid-probability scores and false-negative results for the ARR. Diuretics increased aldosterone, 18-oxocortisol, and steroid-probability scores in patients without PA, whereas angiotensin-converting enzyme inhibitors decreased aldosterone, steroid-probability scores, and ARRs. Beta-adrenoceptor blockers, dihydropyridine calcium channel blockers, and angiotensin receptor blockers had negligible impact on mineralocorticoids and steroid-probability scores. Among antihypertensive drugs that impact plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol, mineralocorticoid receptor antagonists stood out as a cause of false-positive results for derived steroid-probability scores. Other antihypertensives have minimal or no impact, an advantage for use of steroid-probability scores over the ARR when those medications cannot be withdrawn. URL: https://drks.de/search/en/trial/DRKS00017084; Unique identifier: DRKS00017084.

The effect of pre-hospital use of RAS inhibitors on COVID-19 mortality.

The effect of pre-hospital use of renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)) on clinical outcomes of hypertensive patients with COVID-19 has been questioned due to conflicting reports on this issue. After applying exclusion criteria, 175 COVID-19 hospitalized patients admitted to the Tishreen Hospital from January 1 to July 31, 2021 were retrospectively enrolled in this study. Baseline characteristics and in-hospital mortality rate were assessed between hypertensive (N = 91, 52%) and non-hypertensive (N = 84, 48%) patients, as well as between patients taking ACEis/ARBs and non-ACEis/ARBs within the hypertensive group. A lower mortality rate (51.2 versus 31.9%, p = 0.009) was observed in the hypertensive group (mean age 64.6 years, 64.8% males) compared to the non-hypertensive (mean age 62.6 years, 66.7% males). Patients' mortality in the non-hypertensive group was associated with lower blood oxygen saturation (SPO2 = 75 versus 86%, p = 0.002), increased levels of inflammatory (CRP, white blood cell and neutrophils count), and tissue/renal injury markers (LDH, urea, and creatinine). In the hypertensive group, a lower mortality rate was noted in the ACEis/ARBs group compared to the non-ACEis/ARBs (24.1 versus 45.5%, p = 0.036), and this was associated with a decrease in D-DIMER levels, although not significant (1723 versus 2683 ng/mL, p > 0.05). Death in the non-ACEis/ARBs group was associated with decreased SPO2 and tissue/renal injury markers (LDH, CK, AST, urea, and creatinine). We concluded that hypertension is not a direct cause of poor prognosis in COVID-19 patients and that multi-organ damage is a significant indicator of death from COVID-19. RAS inhibitors could improve the survival of hypertensive COVID-19 patients.

Effect of sacubitril/valsartan on hospital readmissions in heart failure with reduced ejection fraction in Saudi Arabia: A multicenter retrospective cohort study.

Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that has been shown in multiple clinical trials to have clinical benefits and is recommended by major clinical management guidelines as a first-line treatment for heart failure with reduced ejection fraction (HFrEF). The most significant benefit that was observed in clinical trials is its effect in reducing hospital readmissions. However, little evidence supports its effectiveness in practice, especially in Saudi Arabia. A multicenter retrospective cohort study was conducted using the patient medical records at 2 tertiary hospitals in Saudi Arabia. Eligible patients were adults (≥18 years old) with a confirmed diagnosis of HFrEF who were discharged on either sacubitril/valsartan or angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) in addition to the other recommended therapy for HFrEF. The primary endpoint was the all-cause 30-day readmission rate. The secondary endpoints included all-cause readmissions at 60-day, 90-day, and 12 months. Additionally, 30-day, 60-day, and 90-day readmissions due to HF were evaluated. A total of 398 patients were included in our analysis; 199 (50.0%) received sacubitril/valsartan (group 1), and 199 (50.0%) received ACEI/ARB (group 2). Our results showed that all-cause 30-day readmissions in group 1 were significantly lower than in group 2 (7% vs 25.0%, RR 0.28, 95% Cl 0.16-0.49; P < .001). Additionally, the secondary outcomes showed significantly fewer 60-day, 90-day, and 12-month all-cause readmissions were identified in group 1 compared to group 2 (11% vs 30.7%, RR 0.36, 95% CI 0.23-0.56; P < .001), (11.6%. vs 32.6%, RR 0.35, 95% CI 0.23-0.55; P < .001) and (23.6% vs 51.2%, RR 0.46, 95% CI 0.35-0.62; P < .001), respectively. Furthermore, HF readmissions at 30-day, 60-day, and 90-day in group 1 were significantly lower than in group 2 (P < .05). Sacubitril/valsartan for the treatment of HFrEF is associated with a significantly lower rate of all-cause readmission as well as HF readmissions compared to ACEI/ARB. These benefits extend up to 12 months post-discharge.