Trends of ARNI and Other Heart Failure Medication Use in Older Adults

In 2015-2017, we identified 276,679 to 315,788 Medicare beneficiaries with HFrEF (mean age 76.6-76.7 years, 75.0-76.2% male, 82.0-83.4% Whites, and 44.8-50.9% frail). Since its approval in July 2015, ARNI use increased from 0.3% to 5.7%. ARNI uptake was lower in patients with older age (6.6% for 65-74 years vs 3.4% for ≥85 years), non-Hispanic race (7.3% for Hispanic vs 5.6-6.6% for other race), no dual eligibility (6.4% for dual eligibility vs 5.5% for no dual eligibility), frailty (5.1% for frailty vs 6.1% for non-frailty) and dementia (3.8% for dementia vs 6.1% for no dementia). Frail patients were less likely than non-frail patients to receive disease-modifying treatments, such as angiotensin-converting enzyme inhibitors (32.4% vs 38.9%), angiotensin receptor blockers (14.5% vs 17.5%), aldosterone antagonists (20.8% vs 23.4%), and beta-blockers (65.1% vs 68.3%), but more likely to receive symptomatic treatment with loop diuretics (56.4% vs 48.0%).

Analysis of current approaches to the treatment and quality of life improvement in patients with gastroesophageal reflux disease in case of its combination with the syndrome of undifferentiated connective tissue dysplasia

When the structure of the connective tissue is disturbed, the probability of developing pathology of the internal organs increases. The gastrointestinal tract is one of the systems that is most often involved in the pathological process in the case of such disorders. Due to its mesenchymal origin, the esophagus is one of the first to suffer. Normalization of mineral metabolism, correction of immunological and bioenergetic status are the main tasks in the treatment of such patients. Therapy with magnesium drugs, vitamins, anabolic drugs, ?-blockers, aldosterone antagonists, and amino acid drugs should also be used for this purpose. Patients in this group should also take drugs that contain vitamin D3

Docking Molecular analysis of potential Aldosterone antagonists

Background: Aldosterone antagonists (spironolactone, eplerenone) inhibit the action of aldosterone in the collecting duct; as such, these agents cause modest diuresis but inhibit potassium and hydrogen ion secretion. We report first time Potential Aldosterone antagonists by in Silico approach, using AutoDock Vina and AutoDock 4 (or MGL Tool), estimated with Pyrx and AM Dock Software, calculating three different important parameters: Binding Affinity ( kcal/mol), estimated Ki ( in nM units) and Ligand Efficiency ( L.E. in kcal/mol). After a selective analysis of over 1000 drugs, processed with Pyrx (a Virtual Screening software for Computational Drug Discovery) in the Ligand Binding site pocket of the protein ( ID PDB 2OAX Chain A:), we noticed high values of Binding Energy , about -13.55 kcal/mol estimated by AutoDock 4 with AM Dock Software, concluding that it could be an excellent candidate drug, compared to everyone else Aldosterone antagonists. Indeed, from the results of AutoDock Vina and AutoDock 4 ( or AutoDock 4.2 ), implemented with Lamarckian genetic algorithm, LGA, trough AMDock Software, our results of Binding Energy are very similar to the crystallized Spironolactone in PDB 2OAX Chain A protein.

Trends in the medical therapy of patients who discharge from hospital after decompensated heart failure

Funding Acknowledgements Type of funding sources: None. Background Acute heart failure is one of the most common causes of cardiovascular hospitalization. An important factor in the prevention of re-admissions is the optimal medical therapy of heart failure patients. Purpose To evaluate medication in patients after hospitalization for acute decompensated heart failure. Methods We studied consecutive patients who admitted and discharged from two tertiary hospitals due to decompensated heart failure from June 2019 to December 2020. Their medication was recorded at the time of discharge and one month later. Results Overall, 730 patients (61% men), with mean age of 77 ± 12 years, were studied. At discharge, the vast majority of the patients (94%) received diuretic, while 45% of them received either angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) or sacubitril/valsartan (20%, 12% and 13%, respectively). 74% of the patients received b-blockers, half of the patients (51%) received aldosterone antagonists, 12% Sodium-glucose Cotransporter-2 inhibitors (SGLT2i) , 6% cardiac glycosides, and only 3% ibavradine. In one month of reassessment, the corresponding percentages were: 90% diuretics, 25% ACEI, 16% ARB, 18% sacubitril/valsartan, 78% b-blockers, 53% aldosterone antagonists, 14% SGLT2i, 4% cardiac glycosides and 3% ibavradine. Despite the low dosing regimens at discharge, after one month, the majority of the patients already receiving ACEI, ARB, sacubitril/valsartan and beta-blockers were up-titrated, while a dose reduction was noticed on diuretics in almost all patients. Conclusion There are still considerable margins to improve management of the optimal medical treatment of patients who discharge from hospital after acute heart failure.

Incidence and impact of acute cardiorenal syndrome

Funding Acknowledgements Type of funding sources: None. Background Acute (or type 1) cardio-renal syndrome (ACRS) is defined as the acute kidney injury in patients hospitalized for acute heart failure (HF), which often is associated to a complex and complicated clinical course. In addition, renal failure is a strong predictor of long-term adverse events in patients with acute heart failure (HF). Purpose To investigate the impact of ACRS, what factors are related to its occurrence, and how it affects the outcome of patients hospitalized with acute HF. Methods We studied consecutive patients hospitalized with acute HF from January 2019 to December 2020. Renal function as well as other biomarkers were recorded and monitored during hospitalization, and correlated with various clinical characteristics, risk factors and patient outcome. Results The sample consists of 612 patients, mean age 77 ± 12 years, 63% men with average duration of hospitalization 6 ± 4 days. A total of 37 deaths (6%) were observed. ACRS was found in 141 patients (23%) and independent prognostic factors for its occurrence were ischemic cardiomyopathy, age, prolonged hospitalization, use of aldosterone antagonists and high CRP upon admission. The incidence of ACRS during hospitalization was an independent prognostic factor of death (r = 0.15, p = 0.02) and anemia (r = 0.24, p = 0.04), while the outcome of death was more common in patients with ACRS - but without statistical significance - compared to patients without ACRS. Conclusion Deterioration of renal function in acute HF is associated with anemia and death. Factors such as ischemic cardiomyopathy, age, length of hospital stay seem to play a role in the onset of ACRS and should be taken into account in these patients, to prevent negative outcomes.

The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer

Cancer is a complex group of diseases that constitute the second largest cause of mortality worldwide. The development of new drugs for treating this disease is a long and costly process, from the discovery of the molecule through testing in phase III clinical trials, a process during which most candidate molecules fail. The use of drugs currently employed for the management of other diseases (drug repurposing) represents an alternative for developing new medical treatments. Repurposing existing drugs is, in principle, cheaper and faster than developing new drugs. Antihypertensive drugs, primarily belonging to the pharmacological categories of angiotensin-converting enzyme inhibitors, angiotensin II receptors, direct aldosterone antagonists, β-blockers and calcium channel blockers, are commonly prescribed and have well-known safety profiles. Additionally, some of these drugs have exhibited pharmacological properties useful for the treatment of cancer, rendering them candidates for drug repurposing. In this review, we examine the preclinical and clinical evidence for utilizing antihypertensive agents in the treatment of cancer.

MO817ALDOSTERONE ANTAGONISTS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE REQUIRING DIALYSIS

Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.

Acute Coronary Syndrome follow up: Portuguese experience

Funding Acknowledgements Type of funding sources: None. OnBehalf Portuguese Registry of Acute Coronary Syndromes Background Acute coronary syndrome is a major health problem, with several acute and chronic complications. So, it is imperative identifying factors that can be associated with better and worse prognosis during the follow up these patients. Objective Evaluate predictors of mortality, cardiovascular readmission and all causes of readmission at 1 year follow up in ACS patients. Methods Multicenter retrospective study, based on the Portuguese Registry of ACS between 1/10/2010-4/09/2019. Logistic regression was performed to assess predictors of mortality, cardiovascular readmission and all causes of readmission at 1 year follow up in ACS patients. Results 1492 patients were included, 141 die during the first year. Age > 75 years old (odds ratio (OR) 2.557, p < 0.001, confidence interval (CI) 1.727-3.785), heart rate < 60 (OR 2.686, p = 0.008, CI 1.296-5.569), cardiogenic shock (OR 6.726, p = 0.012, CI 1.512-29.915), creatinine >2mg/dL (OR 1.956, p = 0.023, CI 1.099-3.480), left ventricular ejection fraction <50% (OR 1.911, p = 0.001, CI 1.284-2.844), nitrate (OR 1.589, p = 0.020, CI 1.074-2.351), ivabradine (OR 1.831, p = 0.011, CI 1.146-2.924), aldosterone antagonists (OR 1.632, p = 0.020, CI 1.079-2.468), diuretic (OR 1.625, p = 0.023, CI 1.069-2.472) and mechanical complication d (OR 55.518, p < 0.001, CI 11.516-267.655) were predictors of mortality of 1 year of follow up. Regarding cardiovascular readmission was registered in 291 patients, of a total 1412. Were predictors of cardiovascular readmission previous history of heart failure (OR 1.467, p = 0.003, CI 1.135-1.895), cardiogenic shock (OR 3.447, p = 0.039, CI 1.068-11.128), acetylsalicylic acid previous to ACS (OR 1.751, p = 0.008, CI 1.285-2.385), multivessel disease (OR 1.667, p = 0.002, CI 1.206-2.306), left ventricular ejection fraction <50% (OR 1.489, p = 0.003, CI 1.145-1.938), nitrate (OR 1.812, p < 0.001, CI 1.403-2.341), aldosterone antagonists (OR 1.572, p = 0.004, CI 1.155-2.140) and sustained ventricular tachycardia (OR 55.518, p < 0.001, CI 11.516-267.655). On the other hand 411 patients was readmitted (all causes), in 1455 patients with follow up. Were predictors of all causes of readmission previous history of heart failure (OR 1.347, p = 0.025, CI 1.039-1.747), previous chronic obstructive pulmonary disease (OR 1.456, p = 0.041, CI 1.016-2.087), atrial fibrillation (OR 1.439, p = 0.027, CI 1.041-1.988), acetylsalicylic acid previous to ACS (OR 1.473, p = 0.001, CI 1.161-1.869), left ventricular ejection fraction <50% (OR 1.456, p = 0.001, CI 1.166-1.819), nitrate (OR 1.478, p < 0.001, CI 1.192-1.831), aldosterone antagonists (OR 1.493, p = 0.003, CI 1.148-1.943) and sustained ventricular tachycardia (OR 3.792, p = 0.004, CI 1.540-9.337). Conclusions: Left ventricular ejection fraction <50%, nitrate as discharge therapeutic and aldosterone antagonists as discharge therapeutic were predictors of mortality, cardiovascular readmission and readmission for all causes at 1 year follow up.