Aldosterone System Inhibitors Research Articles

Use of sacubitril/valsartan in patients with heart failure: evidence from the real world

ABSTRACT Background To characterize the use of sacubitril/valsartan in a group of patients with heart failure in Colombia. Research design and methods Follow-up study of patients with heart failure who started sacubitril/valsartan and were affiliated with the Colombian health system between 2019 and 2021. Sociodemographic, clinical, and pharmacological variables and adherence and persistence of use were identified. Results A total of 514 patients were identified, with a mean age of 65.7 years, 73.7% of whom started sacubitril/valsartan at low doses, and only 12.5% reached the maximum dose. Adherence was 78.2% and persistence was 56.8% at 1 year of follow-up. The increase in systolic blood pressure (odds ratio (OR): 1.01; 95% CI: 1.00–1.03) and the use of β-blockers (OR: 2.63; 95% CI: 1.42–4.85) were correlated with a greater persistence, while receiving furosemide (OR: 0.59; 95% CI: 0.39–0.89) and not having received renin – angiotensin – aldosterone system inhibitors in the 3 months before starting sacubitril/valsartan (OR: 0.48; 95% CI: 0.31–0.76) were associated with lower persistence. Conclusions The persistence of treatment 1 year after starting sacubitril/valsartan was not high, and a small proportion of patients reached the target dose of the drug. Nontitration of the drug dose was common.

Coronavirus disease 2019 and cardiovascular disease: what we have learnt during the last 2 years.

Coronavirus disease 2019 and cardiovascular disease: what we have learnt during the last 2 years.

Etiology of Persistent Microalbuminuria in Nigeria (P_MICRO study): protocol and study design

BackgroundMicroalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4–8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and kidney disease, including diabetes, APOL1 high-risk genotype, and smoking were rare. Co-infection with endemic pathogens may also be significant contributors to albuminuria, but co-infections were not evaluated in the R3 study population.MethodsIn Aim 1, we will cross-sectionally compare the prevalence of albuminuria and established kidney disease risk factors in a cohort of PWH to age- and sex-matched HIV-negative adults presenting for routine care at the Aminu Kano Teaching Hospital in Kano, Nigeria. We will leverage stored specimens from 2500 R3 participants and enroll an additional 500 PLWH recently initiated on ART (≤ 24 months) and 750 age- and sex-matched HIV-negative adults to determine the contribution of HIV, hypertension, and other comorbid medical conditions to prevalent albuminuria. In Aim 2, we will follow a cohort of 1000 HIV-positive, ART-treated and 500 HIV-negative normoalbuminuric adults for 30 months to evaluate the incidence and predictors of albuminuria.DiscussionThe findings from this study will support the development of interventions to prevent or address microalbuminuria in PWH to reduce kidney and cardiovascular morbidity and mortality. Such interventions might include more intensive monitoring and treatment of traditional risk factors, the provision of renin-angiotensin aldosterone system or sodium-glucose cotransporter-2 inhibitors, consideration of changes in ART regimen, and screening and treatment for relevant co-infections.

Effects of Renin-Angiotensin-Aldosterone System Inhibitors on Long-Term Major Adverse Cardiovascular Events in Sepsis Survivors.

BackgroundSepsis is known to increase morbidity and duration of hospital stay and is a common cause of mortality worldwide. Renin‐angiotensin‐aldosterone system inhibitors (RAASis) are commonly used to treat hypertension but are usually discontinued during hospitalization for sepsis because of concerns about renal hypoperfusion. The aim of our study was to investigate whether RAASis should be continued after discharge in sepsis survivors and to identify the effects on the clinical outcomes.Methods and ResultsA total of 9188 sepsis survivors aged 20 years and older who were discharged from January 1, 2012 to December 31, 2019 were included in our analyses. We further divided sepsis survivors into RAASi users and nonusers. These groups were matched by propensity scores before the outcomes of interest, including all‐cause mortality and major adverse cardiac events (MACE), were examined. After propensity score matching, 3106 RAASi users and 3106 RAASi nonusers were included in our analyses. Compared with RAASi nonusers, RAASi users had lower risks of all‐cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.62–0.75), MACEs (HR, 0.87; 95% CI, 0.81–0.94), ischemic stroke (HR, 0.85; 95% CI, 0.76–0.96), myocardial infarction (HR, 0.74; 95% CI, 0.61–0.90), and hospitalization for heart failure (HR, 0.84; 95% CI, 0.77–0.92). Subgroup analyses stratified by admission to the ICU and the use of inotropes showed similar results.ConclusionsIn our study, we found that RAASi users had reduced risks of all‐cause mortality and MACEs. These findings suggested a beneficial effect of RAASi use by sepsis survivors after discharge.

Characteristics and Outcomes of Survivors of Critical Illness and Acute Kidney Injury Followed in a Pilot Acute Kidney Injury Clinic

Characteristics and Outcomes of Survivors of Critical Illness and Acute Kidney Injury Followed in a Pilot Acute Kidney Injury Clinic

MO201ANALYSIS OF USAGE OF SODIUM ZIRCONIUM CYCLOSILICATE (SZC) AT HULL UNIVERSITY TEACHING HOSPITALS

Abstract Background and Aims Renin Angiotensin Aldosterone System (RASS) inhibitor therapy is key to the management of several chronic long term conditions; however, RAAS inhibitors can cause hyperkalaemia and thus limiting its use. Sodium zirconium cyclosilicate, was approved in the UK as part of the management of hyperkalaemia in adults. Although the efficacy and safety of SZC has been demonstrated in clinical trials, there isn’t an abundance of data of its use in clinical practice. This study investigated the efficacy and safety of SCZ in the short-term management of hyperkalaemia in patients admitted acutely to hospital. Method This retrospective study analysed prescriptions and medical notes of patients who received SCZ treatment between June and December 2020 at Hull University Teaching Hospitals. Eligible patients (>16years and received SCZ) were identified from pharmacy dispensing data. Data collected included patient demographics, prescribed medication that could affect serum potassium levels prior to starting SZC, indication, dose of SCZ, potassium level at start and 72hrs after treatment and if the patient was on renal replacement therapy (RRT). In addition, speciality of the prescriber and reported adverse effects were noted. Data analysis was descriptive. Results During the study period, SZC was prescribed to 59 patients on 73 different occasions. Fifty-two (71%) were male, mean age was 58 years (range 17 – 88 years). Twenty-two patients (37%) were on RASS inhibitors, six patients on a potassium sparing diuretic, and 21 on a beta-blocker before treatment with SZC. Thirteen patients (22%) were on a combination of at least two of these medicines. Nineteen patients (32%) were on haemodialysis and four patients (7%) were on peritoneal dialysis (PD) prior to treatment with SZC. The documented reason for SZC use included hyperkalaemia secondary to dialysis access failure, acute kidney injury, pharmacotherapy induced hyperkalaemia and pre-emptive prescribing to allow time to create a new RRT access. Thirty-three (56%) patients had their serum potassium level checked at start and 72hrs after treatment with SZC. The remaining patients had their biochemical profiles checked more than 72 hours after starting SZC with inconsistent time frames and thus, were excluded from the further analysis. In haemodialysis patients, the median serum potassium level at start of treatment with SZC was 5.7mmol/L (range 4.6mmol/L – 6.3mmol/L) while in PD patients the median potassium level 6.4mmol/L (range 4.4mmol/L – 6.4mmol/L). The mean decrease in serum potassium was 0.73mmol/L (range 0.1mmolo/L – 3mmol/L) and 1.7mmol/L (range 0.1 -1.6mmol/L) in HD and PD patients respectively. For patients not on RRT prior to treatment with SZC, and median serum potassium level at start of treatment was 6.0mmol/L (range 5.5mmol/L – 6.7mmol/L). In these patients, a mean decrease in serum potassium of 1.1mmol/L (range 0.2mmol/L – 2.4mmol/L) was observed. Twenty-three patients (70%) received 10g and ten patients received the 5g dose of SZC. Patients who had the 10g doses had a mean reduction in serum potassium of 1.0mmol/L (range 0.1mmol/L - 3.0mmol/L) and patients who received 5g doses had a mean reduction of 0.97mmol/L (range 0.2mmol/L – 1.9mmol/L) over the 72-hour period. There were no reported side effects. It was found that SZC was initiated by a range of specialities (see Figure 1). The nephrology team accounted for the majority (45%) of prescriptions. Notably, the cardiology team initiated only one prescription. Conclusion Our data from clinical practice indicates that SZC is effective and well-tolerated treatment in the management of hyperkalaemia. Our results also suggest that the reduction in potassium level was not vastly different for patients started on the 5g dose vs the 10g dose but this requires further research with larger study sample sizes. Limitations of the study included small sample size and retrospective nature of the study.

Effects of telmisartan on proteinuria and systolic blood pressure in dogs with chronic kidney disease

Renal proteinuria is associated with promoted renal dysfunction and a shorter survival period in dogs with chronic kidney disease (CKD). Renin angiotensin– aldosterone system inhibitors are primarily used to treat renal proteinuria. In this retrospective, open-label study, we aimed to evaluate the anti-proteinuric and anti-hypertensive effects of telmisartan (angiotensin II receptor blocker) in dogs with proteinuric CKD. A total of 28 dogs with proteinuric CKD were included in the study, all dogs received telmisartan 1 mg/kg q24h, PO. The urine protein-to-creatinine ratio (UPC), urine albumin-to-creatinine ratio (UAC) and systolic blood pressure (SBP) decreased significantly after telmisartan administration (P < 0.05). The median rate of change in UPC, UAC and SBP at Day 120 were − 65.1%, −75.9% and − 9.7%. Ten dogs (36.7%) achieved UPC < 1.0 at Day 120, of which six dogs had UPC < 0.5. A reduction of UPC to ≥50% was achieved in 10 dogs (36%) at Day 45 and 17 dogs (61%) at Day 120. Seventeen dogs (61%) had hypertension at baseline, of which 10 dogs (59%) had SBP < 160 mmHg at Day 120. Two-way repeated measures analysis of variance did not attribute the observed changes in SBP, UPC or UAC to feeding with a renal diet. In conclusion, telmisartan therapy provides anti-proteinuric and anti-hypertensive effects in dogs with proteinuric CKD.

Pharmacologic and Perioperative Considerations for Antihypertensive Medications.

As the prevalence of hypertension continues to increase, physicians routinely encounter patients preoperatively receiving one or more cardiovascular medications to manage hypertension. Thus, the physician's knowledge of perioperative antihypertensive medication management is crucial to ensure patient safety. We discuss the decisions to continue or stop antihypertensive medications to reduce the risk of perioperative complications. We conducted a review of the original research studies, review articles, and editorials present on PubMed within the past 60 years. The authors included peer-reviewed articles that they deemed relevant to current practice. Search terms of perioperative surgical home, preoperative medication instruction, surgery, and perioperative management were used in combination with the key words α-agonist, antihypertensive, β-blocker, calcium-channel blocker, diuretic, hypertension, renin-angiotensin-aldosterone system inhibitor, and vasodilator. The reference lists of each selected article were also reviewed for additional sources of information. The number of articles about perioperative management of antihypertension medications increased in more recent years. Evidence showed clear support of the continuation or withholding of most medications. However, no clear recommendation was found on the continuation of reninangiotensin- aldosterone system inhibitors in the perioperative period. Current evidence supports the perioperative continuation of β-blockers, calciumchannel blockers, and α-2 agonists. However, diuretics should be discontinued on the day of the surgery and resumed in the postoperative period. Debates persist about the continuation of reninangiotensin- aldosterone system inhibitors.

Assessment of the effects of antihypertensive drugs in patients suffering from hypertension in Kurdistan

Background and objectives: Hypertension is an important cardiovascular disease that carries a high rate of mortality and morbidity if not controlled. Significant complications of untreated hypertension include vascular atherosclerosis, chronic kidney diseases, and heart failure. The aim of this retrospective study is to improve practitioners' and specialists’ practices in the management of hypertension in the Kurdistan region. This study assesses the response of our local patient population to different first-line and combination therapies for hypertension to identify the most effective approach. Methods: This is a retrospective study conducted on 500 patients diagnosed with hypertension consisting of equal numbers of males and females. The sample was randomly chosen using stratified random sampling methods whereby patients were finally divided according to the drugs they were prescribed into 5 groups: renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, Diuretics, renin-angiotensin-aldosterone system inhibitors + calcium channel blockers and renin-angiotensin-aldosterone system inhibitors+diuretics. The goal was to achieve a blood pressure of less than 140 mmHg systolic and less than 90 mmHg diastolic, which was maintained for 6 months. The data was inputted into SPSS as categorical variables and analyzed by Chi-square test. Results: All the drug groups were significantly effective in bringing the blood pressure to the goal. In relation to mono-therapy calcium channel blockers achieve the goal in (82%) and were the most effective drug group in controlling blood pressure, whilst renin-angiotensin-aldosterone system inhibitors + calcium channel blockers achieve the goal in (85%) was the most powerful combination for controlling moderate to severe hypertension. All age groups were responding to treatment. Conclusions: All the drug groups tested either singly or in combination calcium channel blockers were best for monotherapy, whereas renin - angiotensin - aldosterone system inhibitors + calcium channel blockers were the best effective combination therapy.

Dual Angiotensin Receptor and Neprilysin Inhibition with Sacubitril/Valsartan in Chronic Systolic Heart Failure: Understanding the New PARADIGM.

To evaluate the clinical role of sacubitril/valsartan, a novel angiotensin-neprilysin inhibitor, for the treatment of chronic heart failure with a reduced ejection fraction (HFrEF). A search of PubMed was conducted using a combination of the search terms sacubitril, valsartan, LCZ696, neprilysin inhibition, natriuretic peptide system, renin-angiotensin system, and heart failure with reduced ejection fraction. Bibliographies of all retrieved articles were reviewed for relevant literature. All references included were published between 1980 and May 2015. All studies and review articles that contained data describing the use of sacubitril/valsartan in HFrEF were reviewed. HFrEF remains a disease of high morbidity and mortality. Natriuretic peptide (NP) augmentation has emerged as a most promising neurohormonal target in HFrEF. NPs provide vasodilatory, natriuretic, diuretic, and antiproliferative actions to help support the failing heart. Neprilysin, a neutral endopeptidase, is a primary pathway for NP metabolism. Combined inhibition of the renin angiotensin aldosterone system and neprilysin augments the beneficial natriuretic peptide pathway while providing direct antagonism to increases in angiotensin II. In the landmark PARADIGM HF trial, the neprilysin inhibitor sacubitril added to valsartan significantly improved morbidity and mortality over enalapril, a standard of care in HFrEF. Application of these results to clinical practice requires careful considerations of trial design, study patient population, and clinical monitoring. Sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HFrEF but will require careful application to "real-world" populations of HFrEF.

Renin angiotensin aldosterone system in the cardiovascular continuum: An overview of the trial evidence and clinical practice

The renin angiotensin aldosterone system (RAAS) inhibitors represent an invaluable class of drugs in the management of various stages of the cardiovascular disease continuum. Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have unique pharmacodynamics properties. These enable them to block the RAAS system at multiple levels. The ARBs inhibit RAAS in a mechanistically distinct fashion when compared to the ACEIs. Whereas ACEIs decrease the synthesis of angiotensin II, ARBs selectively and competitively bind to the AT1 receptors hence preventing there activation by angiotensin II. The differential effects of these two groups of drugs, resulted in them playing different roles in primary and secondary cardiovascular protection. It is suggested that ACEIs tend to be more “cardioprotective” whereas ARBs may be more “cerebral-protective”.In this review article, we will attempt to enhance understanding of the role of RAAS blockers in most appropriate selection of ACEIs and ARBs according to their attributes and the needs of the clinical situation. We will initially described the role of RAAS activation in the pathophysiology of common cardiovascular disease processes. This will be followed by a review of the major clinical trials of different ACEIs and ARBs in the primary prevention and secondary prevention of cardiovascular diseases.In conclusion, the effects of ACEIs across a wide spectrum of cardiovascular diseases remain indisputable. However, ARBs showed a superior effect to ACEIs with regard to stroke, but their efficacy in certain major clinical end points seems limited.

Polymorphism of the aldosterone synthase gene is not associated with progression of diabetic nephropathy, but associated with hypertension in type 2 diabetic patients

Inhibition of aldosterone system is beneficial in diabetic nephropathy, and aldosterone synthesis is regulated at the gene-encoding aldosterone synthase (CYP11B2). Considering the role of aldosterone in diabetic nephropathy, genetic polymorphism of this gene may contribute to the development and progression of diabetic nephropathy. In this study, we investigated whether it is associated with diabetic nephropathy in type 2 diabetic patients. 197 type 2 diabetic patients and 71 healthy controls were enrolled. The study subjects were divided into four groups: healthy controls with normoalbuminuria (n = 71), normoalbuminuric diabetic group (n = 71), microalbuminuric diabetic group (n = 51) and overt proteinuria group (n = 51). Polymorphism of aldosterone synthase gene was determined using standard PCR technique. Higher frequency of TT genotype and T allele in steroidogenic factor-1 (SF-1) binding site and wild type (WT) in intronic conversion (IC) in CYP11B2 was observed in diabetic patients than controls. However, there was no significant difference in SF-1 and IC genotype among diabetic patients according to the state of diabetic nephropathy. Subgroup analysis based on SF-1 polymorphism demonstrated that TT genotype is associated with higher systolic and diastolic blood pressure and higher plasma aldosterone level. In addition, WT in IC genotype showed a significantly higher urinary albumin excretion rate. Plasma aldosterone level was significantly related with systolic blood pressure. Our study suggests that aldosterone synthase gene polymorphism is not associated with progression of diabetic nephropathy, but it may contribute to the development of hypertension associated with increased aldosterone secretion in type 2 diabetic patients.

Direct renin inhibition: an evaluation of the safety and tolerability of aliskiren

ABSTRACTBackground: Aliskiren, an antihypertensive drug approved in the United States and Europe, is the first in a new class known as direct renin inhibitors. Aliskiren has been evaluated for safety and tolerability in more than 6400 patients. It has demonstrated a favorable safety and tolerability profile alone or in combination with other drugs.Objective: This article reviews the currently available safety and tolerability data for aliskiren.Methodology: Using the search term aliskiren, MEDLINE (no timeframe set) and major cardiovascular congresses (2005–2008) were searched. Articles and abstracts with safety and drug interaction data were included.Findings: Aliskiren may share common adverse effects observed with angiotensin-converting enzyme (ACE)-inhibitor and angiotensin receptor blocker (ARB) therapy. In placebo-controlled trials, those commonly reported for aliskiren at the approved dosage were headache, diarrhea, and fatigue, with incidences similar to those of placebo. Aliskiren has been well tolerated in black, geriatric, diabetic, or obese patients and patients with renal or hepatic impairment. Aliskiren neither inhibits nor induces the cytochrome P450 system; it does not inhibit P-glycoprotein, but is a substrate for this drug transporter. Adding a direct renin inhibitor to another renin–angiotensin–aldosterone system (RAAS) inhibitor may further improve cardiovascular outcomes, renal outcomes, or both, without increasing the incidence of adverse effects.Conclusions: Aliskiren is well tolerated, has an adverse effect profile comparable to that of placebo, and has a low potential for drug interactions. Data from ongoing trials evaluating the effects of aliskiren on surrogate markers, morbidity, and mortality will further define the role of direct renin inhibition in the antihypertensive armamentarium.