Angiotensin-converting Enzyme Inhibitor Therapy Research Articles

Adverse Events After Initiating Angiotensin-Converting Enzyme Inhibitor/Angiotensin II Receptor Blocker Therapy in Individuals with Heart Failure and Multimorbidity

BackgroundCurrent clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. However, evidence is lacking on whether routine follow-up testing reduces therapy-related adverse events in adults with heart failure and if multimorbidity influences the association between laboratory testing and these adverse events. MethodsWe conducted a retrospective cohort study among adults with heart failure from 4 US integrated health care delivery systems. Multimorbidity was defined using counts of chronic conditions. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACEI or ARB therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression. ResultsWe identified 3629 matched adults with heart failure initiating ACEI or ARB therapy between January 1, 2005, and December 31, 2012. Follow-up testing was not significantly associated with 30-day all-cause mortality (adjusted hazard ratio [aHR] 0.45, 95% confidence interval [CI] 0.14; 1.39) and hospitalization with hyperkalemia (aHR 0.73, 95% CI, 0.33; 1.61). However, follow-up testing was significantly associated with hospitalization with acute kidney injury (aHR, 1.40, 95% CI, 1.01; 1.94). Interaction between multimorbidity burden and follow-up testing was not statistically significant in any of the outcome models examined. ConclusionsRoutine laboratory monitoring after ACEI or ARB therapy initiation was not associated with risk of 30-day all-cause mortality or hospitalization with hyperkalemia across the spectrum of multimorbidity burden in a cohort of patients with heart failure.

Posterior urethral valve in children: Using novel biomarkers as an early predictive tool for the onset and progression of chronic kidney disease

This narrative review aims to appraise the current evidence on using biomarkers of obstructive nephropathy to predict the onset and progression of chronic kidney disease (CKD) in infants with posterior urethral valves (PUV). PUV is the most frequently reported congenital anomaly of the kidney and urinary tract (CAKUT) associated with bladder outlet obstruction in male children. It contributes significantly to the CKD burden in childhood. Despite different approaches for its postnatal repair, evidence-based data still suggest a high risk of CKD and end-stage kidney disease (ESKD) later in childhood. In obstructive nephropathy, glomerular and tubulointerstitial lesions contribute to renal impairment. Although it may be difficult to predict these adverse renal outcomes in repaired PUV, detecting and monitoring future CKD appears enhanced using the combination of serum creatinine- or cystatin C-based estimated glomerular filtration rate (eGFR) and albuminuria. Given the drawbacks of these conventional biomarkers, there is a paradigm shift to novel biomarkers as tools for the early identification of glomerular and tubulointerstitial lesions seen in obstructive nephropathy. Most novel biomarkers are yet to be fully applied to routine clinical practice globally. Nevertheless, there is substantial evidence showing that they form part of the emerging diagnostics for obstructive nephropathy. From the reviewed studies, urine transforming growth factor-beta 1 (TGF-β1) is the most prominent biomarker among the novel biomarkers of obstructive nephropathy. However, other novel approaches like the machine learning (ML) model (a form of health-related artificial intelligence) and urodynamic parameters like bladder contractility index hold promise for PUV outcomes prediction (PUVOP). Because of the association of urine TGF-β1 with urine angiotensin level (a biomarker of the renin-angiotensin-aldosterone system [RAAS]), early angiotensin-converting enzyme inhibitor (ACEI) therapy in patients with PUV may potentially retard the progression of CKD and improve renal outcomes. Thus, future research directions will be to explore the role of ACEI as a pre-emptive treatment for poor renal outcomes in post valve-ablation patients and to conduct longitudinal studies that would properly demonstrate these biomarkers as predictors of these outcomes.

Effect of ACE Inhibitor Therapy on Mortality in COVID-19 Patients with Hypertension: Meta-Analysis

Background: Acute respiratory syndrome Corona Virus 2 (SARS-CoV-2) can trigger the occurrence of respiratory infectious disease Coronavirus Disease 2019 (COVID-19). Patients who have comorbid health problems such as hypertension, chronic liver, cardiovascular and diabetes mellitus are more likely to experience deterioration and death. ACE inhibitor therapy in patients with hypertension has a therapeutic effect in lowering blood pressure and is able to reduce mortality rates in COVID-19 patients, but the benefits of ACE inhibitors in patients with COVID-19 are still uncertain. This study aims to determine how much influence ACE inhibitors have on COVID-19 patients with hypertension on mortality rates.Subjects and Method: This study is a systematic review and meta-analysis with the following PICO, population: COVID-19 patients with hypertension. Intervention: administration of ACE inhibitor therapy. Comparison: therapy other than ACE inhibitors. Outcome: mortality. The articles used in this study were obtained from several online databases, including Science Direct, PubMed and Google Scholar. The keywords used in the article search were: “ACE inhibitor” AND “COVID-19” AND “Hypertension” AND “mortality”. The articles included are full-text English with a cohort study design from 2020 to 2021 and report the odds ratio in multivariate analysis. The selection of articles was carried out using the PRISMA flow chart. The articles were analyzed using the Review Manager 5.4. application.Results: A total of 4 cohort studies involving 4,998 COVID-19 patients from America, China and Italy were selected for systematic review and meta-analysis. The data collected yielded information that COVID-19 patients with hypertension who were given ACE inhibitors reduced the risk of mortality 0.67 times compared to COVID-19 patients with hypertension who were not treated with ACE inhibitors (aOR= 0.67; 95% CI= 0.36 to 1.26; p= 0.210).Conclusion: ACE inhibitors can reduce the risk of mortality in COVID-19 patients with hypertension. Keywords: COVID-19, hypertension, ACE inhibitors, mortality. Correspondence:Dwi Trisnawati Zainal. Social Security Administrator for Health, Madiun, East Java. Jl. Timor 6 Madiun, East Java, Indonesia. Email: dwitrisnawatiz@gmail.com. Mobile: 081331282009.

An unusual cause of renovascular hypertension in a pediatric patient with chronic kidney disease

Background: Renovascular hypertension (RVH) accounts for 5–10% of arterial hypertension in children and is most commonly caused by fibromuscular dysplasia. Sporadically, renal artery stenosis in pediatric patients is caused by extrinsic compressive masses. Case report: A 12-year-old patient with complex urinary tract defect (dysplastic left kidney — nephrectomy at 11 months, right ectopic kidney in the midline, behind the urinary bladder), chronic kidney disease (CKD) stage 2, and arterial hypertension was admitted to the hospital due to worsening of kidney function during angiotensin-converting enzyme inhibitor (ACE-I) therapy. CT angiography revealed a right ectopic kidney located above the bladder, supplied by a single renal artery originating from the right common iliac artery. The renal artery had a tortuous shape with width in the ostium approx. 4.5 mm; then, the artery was bent and ran between the common iliac artery and the kidney. Ultrasound performed with a filled bladder showed bending and stenosis of the renal artery at the origin from the right common iliac — peak systolic velocity (PSV) 4.5–5.5 m/s and renal-aortic ratio (RAR) 3.1. With an empty bladder, no bending or stenosis was visible (PSV 1.7–1.9 m/s and RAR 1.0). Uroflowmetry revealed a dysfunctional micturition curve, large bladder capacity, and post-void urine retention. ACE-I was changed to beta-blocker and doxazosin, which led to blood pressure and kidney function normalization. Conclusions: Renal ectopia associated with bladder dysfunction may result in renal artery stenosis causing renovascular hypertension.

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

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

Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial

Clinical guidelines recommend titration of angiotensin converting enzyme inhibitors (ACEi) and beta-blockers among patients with heart failure with reduced ejection fraction (HFrEF) to maximally tolerated doses. Patient characteristics associated with dose titration and clinical outcomes subsequent to dose titration remain poorly characterized. Among 1999 ambulatory patients with chronic HFrEF in the HF-ACTION trial, use and dosing of ACEi and evidence-based beta-blockers were examined at baseline and 6-month follow-up. Multivariable logistic regression models were used to assess factors associated with dose escalation (medication initation or dosing increase) or dose de-escalation (medication discontinuation or dosing decrease). Cox proportional hazard regression models were used to examine associations between dose trajectory group (stable target, stable sub-target, dose escalation, and dose de-escalation) and subsequent mortality and hospitalization outcomes. For both ACEi and beta-blockers, hospitalization for heart failure in the 6 months prior to enrollment (odds ratio [OR] 2.32 [95% confidence interval 1.58-3.42]) for ACEi; 1.42 [1.05-1.9] for beta-blockers) and higher systolic blood pressure (OR 1.01 [1.00-1.03] per 1 mmHg increase for ACEi; 1.01 [1.00-1.02] for beta-blockers) were associated with dose escalation. Hospitalization 6 months prior to enrollment for any cause (including HF or non-HF causes) was associated with dose de-escalation (OR 1.60 [1.14-2.25] for ACEi; 1.67 [1.20-2.33] for beta-blockers). After adjustment for patient characteristics, compared with stable target dosing, dose de-escalation of either medication was associated with greater all-cause mortality (adjusted hazard ratio [aHR] 1.64 [1.11-2.42] for ACEi; 1.62 [1.04-2.53] for beta-blockers). Compared with stable target dosing, both dose de-escalation (aHR 1.98 [1.36-2.87]) and stable sub-target dosing (aHR 1.49 [1.18-1.87]) of beta-blockers were associated with greater cardiovascular mortality or hospitalization for heart failure. Among outpatients with chronic HFrEF, patient characteristics including recent hospitalization status and blood pressure were associated with odds of subsequent escalation and de-escalation of ACEi and beta-blocker therapy. Compared with patients receiving guildeline-recommended target doses, dose de-escalation of either medication and sub-target dosing of beta-blockers were associated with greater morbidity and mortality over long-term follow-up.

Angiotensin-converting enzyme inhibitor therapy after heart transplant: From molecular basis to clinical effects.

The use of angiotensin-converting enzyme inhibitors is an important therapy for various cardiovascular diseases, such as hypertension, ischemic heart disease and heart failure (HF). In heart transplant recipients, angiotensin-converting enzyme inhibitors have been demonstrated to be a keystone for the treatment of hypertension with a wide spectrum of pleiotropic molecular effects ranging from improvement of the peripheral vascular system to regulation of the fluid and sodium balance. In addition, angiotensin-converting enzyme inhibitors may be also useful in the prevention of graft failure, cardiac allograft vasculopathy (CAV) and chronic kidney disease (CKD) progression. Further tailored multicenter and randomized studies are warranted to confirm the pleiotropic clinical effects of ACEi therapy in HTRs and to support more extended use in daily clinical practice. Finally in the near future, the use of novel pharmacological agents that inhibit the renin-angiotensin-aldosterone system (RAAS) such as the neprilysin inhibitor sacubitril should be investigated in heart transplant recipients.

MO209: Baseline Characteristics of Adults Enrolled in the Ongoing Phase 3 Randomized, Double-Blind, Active-Control Trial of Sparsentan For the Treatment of Immunoglobulin A Nephropathy (PROTECT)

Abstract BACKGROUND AND AIMS Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease worldwide. Despite optimized standard of care treatment, up to 40% of individuals with IgAN develop kidney failure requiring dialysis or kidney transplantation, consequently seriously affecting their quality of life and mortality. Treatments that reduce proteinuria and risk of kidney disease progression are urgently needed for IgAN. Sparsentan is a novel Dual Endothelin Angiotensin Receptor Antagonist (DEARA) being investigated for IgAN. The Phase 3 PROTECT study is examining the potential long-term antiproteinuric and nephroprotective potential and safety of sparsentan compared with an active control, angiotensin receptor blocker (ARB) irbesartan, in adults with IgAN. Here we report the baseline characteristics for all patients enrolled in the PROTECT trial. METHOD PROTECT is an ongoing, global, Phase 3, multicenter, randomized, double-blind, parallel-group, active controlled study designed to evaluate the efficacy and safety of sparsentan versus the active control irbesartan in adults with IgAN with overt proteinuria despite receiving maximized treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or ARB. The study duration is 270 weeks: a double-blind period of 114 weeks followed by an open-label extension period of up to 156 weeks. The primary efficacy endpoint is the change from baseline in urine protein/creatinine ratio (UP/C) based on a 24-h urine sample at Week 36. Key inclusion and exclusion criteria are shown in Table 1. Patients took their last dose of maximized standard-of-care treatment with ACEi and/or ARB therapy the day before randomization. Patients were randomized 1:1 to sparsentan or irbesartan (target dose 400 and 300 mg/day, respectively), stratified by screening eGFR and urine protein excretion values. The blinded and aggregated baseline characteristics of all the patients enrolled in the PROTECT trial are summarized descriptively. RESULTS A total of 406 patients from clinical sites in 18 countries, including sites in North America, Europe and Asia Pacific, were enrolled in PROTECT and 404 patients were included in the primary analysis population. Selected demographic and clinical characteristics are reported in Table 2. CONCLUSION PROTECT is the largest interventional trial testing a novel drug to date in IgAN. Patients with IgAN enrolled in the PROTECT trial display demographic and clinical characteristics consistent with those previously reported in the broader high-risk IgAN patient population. The presentation despite implementation of optimized standard of care treatment demonstrates the burden of IgAN and the unmet need for novel therapies in this patient population.

Complications of Chronic Kidney Disease: Therapeutic Approaches and What Can Be Done to Halt Disease Progression?

Singapore is one of the most rapidly ageing societies in the world. Currently, Singapore ranks first in the world for the incidence of diabetes-induced end-stage renal disease (ESRD) and seventh for the incidence of kidney failures per million population. It is estimated that nearly one-quarter of Singapore’s population will have chronic kidney disease (CKD) by 2035. Disease management of CKD has been identified as a critical issue due to the rapid increase in cases among the elderly in recent years. Chronic kidney disease is associated with adverse clinical outcomes, and metabolic complications such as anaemia, cardiovascular events, and CKD-associated metabolic bone diseases present treatment management complexities to healthcare professionals. Early detection and management of CKD can avert complications before symptoms occur and prevent the progressive loss of kidney function over time. Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) are recommended for hypertension and proteinuria management in CKD patients with and without diabetes. However, neither of these agents alone reduces the risk of all-cause mortality; furthermore, combinational therapy of ACEI plus ARB is associated with renal dysfunction, stroke, and/or hyperkalaemia. Recently, the use of sodium–glucose cotransporter 2 inhibitors (SGLT2i) has been shown to provide favourable effects on the kidney and cardiovascular outcomes in patients with or without type 2 diabetes mellitus. Studies have shown that early initiation of SGLT2i may slow or halt the progression of CKD in patients with the risk of CKD and ESRD. This review discusses the mechanisms underlying the progression of CKD, its associated risk factors and summarises the management strategies as per Kidney Disease Outcomes Quality Initiative clinical practice guideline recommendations. This article also summarises the evidence regarding the use of SGLT2i in slowing the progression of CKD and improvement of health-related quality of life.

The divergent protective effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on clinical outcomes of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis.

Some studies have speculated that patients on angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are more susceptible to adverse outcomes of coronavirus disease 2019 (COVID-19). Here, we performed a systematic review and meta-analysis to evaluate the safety and efficacy of administering ACEIs and ARBs to patients with COVID-19. Studies of COVID-19 were collected from the PubMed, Embase, medRxiv and BioRxiv databases. The pooled relative risk odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Subgroup analyses were conducted by medication (ACEIs and ARBs) and geographical location (China and outside China). Inter-study heterogeneity was assessed using meta-regression. Begg's test, Egger's test and funnel plots were adopted to evaluate possible publication bias. Thirty studies containing 10,434 adult patients were included in our meta-analysis. The pooled result indicated that the administration of ACEIs or ARBs reduced the risk of severe/death outcomes for COVID-19 patients. Meanwhile, a significant reduction in the risk of severe/death outcomes was observed to be associated with the administration of ACEIs or ARBs among COVID-19 patients in China, but this association was weaker for studies outside China. Furthermore, ACEI therapy was found to carry a significantly lower risk of an adverse clinical outcome. Our systematic review and meta-analysis found that neither ACEIs nor ARBs worsen the clinical outcomes of COVID-19 patients. On the contrary, we found that patients treated with ACEIs or ARBs have a reduced risk of severe/death outcomes, especially in Asia. Furthermore, ACEIs may reduce the risk of severe/death outcomes. Therefore, treatment interruption of ACEI or ARB therapy during COVID-19 infection is not recommended.

Cardiac Atrophy and ACE Inhibitors in Duchenne Cardiomyopathy: 10 Years is the Right Age to Start Therapy?

<h3>Purpose</h3> <b>Background</b> Dilated cardiomyopathy (DCM) is a leading cause of morbidity and mortality in patients affected by Duchenne muscular dystrophy (DMD). DCM is commonly characterized by a hypokinetic and dilated phenotype, typically involving left ventricle (LV). Nowadays, angiotensin converting enzyme inhibitors (ACEi) are indicated in all patients older than 10 years but the mechanism of action is still unknown. Characteristics of left ventricular (LV) remodelling are unclear, and no data are currently available on the time of onset. <b>Aim:</b> characterize left ventricular remodelling before 10 years of age and the effects of ACEi on it. <h3>Methods</h3> We conducted a retrospective single center analysis on all consecutive patients affected by DMD-DCM before 10 years of age, without LV dilation. We reanalysed all echocardiographic data about LV dimension and function, at the first cardiovascular assessment (before ACEi), at one year after treatment, and at the last follow up. To evaluate LV remodelling, we derived the relative wall thickness (RWT). RWT< 0.32 was the cut off to define the cardiac atrophy. <h3>Results</h3> 45 patients have been enrolled. Median age at first CV assessment was 10.3 y (±2.9). 72% of patients presented a reduced RWT (< 0.32) at first CV evaluation (average value 0.29 ± 0.05). After 1 year of treatment the percentage of patient with cardiac atrophy was unchanged (p = 0.52): 6 patients progressed and 6 regressed. At last follow up (35.5 months, ±7.7) the prevalence of cardiac atrophy was slightly increased (78% - p = 0.15): 9 patients (28%) developed cardiac atrophy during follow-up, despite ACEi therapy, while 6 (19%) regressed. Notably, neither progression nor regression were statistically significant (p= 0.15, p = 0.4 respectively). All patients were treated with ACEi: 48% was treated with Enalapril, 26% with Ramipril, 17% with perindopril, and the remaining with Fosinopril or Lisinopril. Median age at ACEi start was 11.2 (± 2.9). <h3>Conclusion</h3> Our data suggest that cardiac atrophy is already present, before 10 years of age. ACEi seems to slow progression but not invert the process.

Renin-Angiotensin Blockade Reduces Readmission for Acute Chest Syndrome in Sickle Cell Disease.

RationaleAcute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Current treatment is supportive-supplemental oxygen, transfusions, and antibiotics. Prevention of ACS may reduce morbidity and mortality in patients with SCD.Acute chest syndrome appears similar to pulmonary fat embolism (PFE), a complication of severe skeletal trauma or orthopedic procedures from pulmonary micro-vessel blockage by bone marrow fat. Vascular obstruction and bone marrow necrosis occur in PFE and ACS. Pulmonary fat embolism rat models have shown that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) mitigate damage in PFE. These medications could work similarly in ACS. We hypothesize that time to readmission after one hospitalization for ACS will be reduced in patients taking ACEI or ARB compared to patients who are not.MethodsThis is a retrospective cohort study. Inclusion criteria are adults (18 to 100 years) with sickle cell anaemia (HbSS), hemoglobin SC (HbSC) disease, sickle cell thalassemia (HbSβThal), hospitalized with ACS over 16 years (January 1, 2000, to March 31, 2016); patients who take and don’t take ACEI or ARB. Children (<18 years old), elderly adults (>100 years old), pregnant patients, and patients with sickle cell trait were excluded.Data was collected from the Health Facts database, which contains de-identified information from the electronic medical records of hospitals in which Cerner© has a data use agreement.Kaplan-Meier estimates explored a time-to-event model of ACS readmission. Multivariable analysis (age, gender, smoking history) was conducted using Cox proportional hazards regression. Results were reported around a 95% confidence interval.ResultsThere were 6972 patients in total. Of which, 9.6% (n = 667) reported taking ACEI or ARB. Results for the covariates were: average age of 38 years old; 63% female (n = 4366/6969); 16% smokers (n = 1132).Readmission rates were higher for patients not taking ACEI/ARB than those who did: 0.44 (95% CI 0.43, 0.46) versus 0.28 (95% CI 0.24, 0.31) at one year, and 0.56 (95% CI 0.55, 0.58) versus 0.33 (95% CI 0.29, 0.37) at two years. Age had the strongest effect on readmission rates for patients taking ACEI/ARB (adjusted hazards ratio 0.78 [95% CI 0.68, 0.91]).ConclusionPatients with SCD who reported taking ACEI or ARB had lower readmission rates for ACS; age was the strongest covariate. Our results may have a significant impact on the prevention of ACS. Prospective studies comparing ACEI or ARB therapy versus placebo are needed to confirm this preventative effect.

Incidence of angiotensin-converting enzyme inhibitor-induced cough in a Malaysian public primary care clinic: A retrospective cohort study

Introduction: The incidence of angiotensin-converting enzyme inhibitors (ACEi)-induced cough has been reported between 5% and 30% but is unknown in Malaysia. This study aimed to determine the incidence of ACEi-induced cough and its associated factors in a public primary care clinic in Malaysia. Methods: A retrospective review of electronic medical records of patients who were initiated ACEi between January 1, 2015, and December 31, 2015, and reviewed until July 31, 2016. A total of 1,091 patients were newly prescribed ACEi, and 394 patients were eligible for this study. We excluded patients who defaulted follow-ups with no further clinic visits before July 31, 2016, were transferred to the clinic without the recorded date of ACEi initiation, were transferred to other clinics during the study period, were followed up at other clinics and attended the study clinic for a short period, or were given only a stat dose of ACEi. Results: Among the 394 patients initiated on ACEi, 225 (57.1%) were male, 369 (93.7%) were Malay, 376 (95.4%) had hypertension, and 192 (48.7%) had diabetes. The incidence of ACEi-induced cough was 24.1%, and 42 (10.7%) patients developed cough on the day of therapy initiation. There was no association between age, gender, ethnicity, type of ACEi, and cough. Conclusion: Approximately one quarter of patients developed cough after ACEi initiation, and approximately half of them developed cough within 1 week of ACEi initiation. Doctors should consider early follow-up for patients initiated on ACEi therapy to ensure adherence, quality of life, and minimise unnecessary treatment.

Anti-microRNA-21 Therapy on Top of ACE Inhibition Delays Renal Failure in Alport Syndrome Mouse Models.

Col4a3−/− Alport mice serve as an animal model for renal fibrosis. MicroRNA-21 (miR-21) expression has been shown to be increased in the kidneys of Alport syndrome patients. Here, we investigated the nephroprotective effects of Lademirsen anti-miR-21 therapy. We used a fast-progressing Col4a3−/− mouse model with a 129/SvJ background and an intermediate-progressing F1 hybrid mouse model with a mixed genetic background, with angiotensin-converting enzyme inhibitor (ACEi) monotherapy in combination with anti-miR-21 therapy. In the fast-progressing model, the anti miR-21 and ACEi therapies showed an additive effect in the reduction in fibrosis, the decline of proteinuria, the preservation of kidney function and increased survival. In the intermediate-progressing F1 model, the anti-miR-21 and ACEi therapies individually improved kidney pathology. Both also improved kidney function and survival; however, the combination showed a significant additive effect, particularly for survival. RNA sequencing (RNA-seq) gene expression profiling revealed that the anti-miR-21 and ACEi therapies modulate several common pathways. However, anti-miR-21 was particularly effective at normalizing the expression profiles of the genes involved in renal tubulointerstitial injury pathways. In conclusion, significant additive effects were detected for the combination of anti-miR-21 and ACEi therapies on kidney function, pathology and survival in Alport mouse models, as well as a strong differential effect of anti-miR-21 on the renal expression of fibrotic factors. These results support the addition of anti-miR-21 to the current standard of care (ACEi) in ongoing clinical trials in patients with Alport syndrome.

Early echocardiographic predictors of unfavorable yearly prognosis in patients with acute myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Objective to determine the most informative in the prognostic plan echocardiographic indices in patients with acute myocardial infarction and diabetes mellitus. Methods A retrospective analysis of outcomes of 97 diabetic patients with acute myocardial infarction (AMI), with lesions of two or more coronary arteries was performed. All patients received conventional basic therapy comprising, acetylsalicylic acid, clopidogrel, beta-blocker, an ACE inhibitor, statins, and insulin therapy on a stationary phase for a minimum of 2 weeks, followed by a transition to oral antidiabetics. According to the 12 month follow depending on the outcomes two groups were established: favorable prognosis n = 46 and unfavorable prognosis n = 51, having one or more of the following complications: death, reinfarction (nonfatal), development or progression of heart failure. Results Differences in echocardiographic parameters, characterizing myocardial hypertrophy of left ventricular (LV) were revealed between patients with different outcomes of AMI. Thus, patients with adverse outcome were characterized by a significant increase of LV mass (from 191.2 ± 35.7g to 255.7 ± 46.2 g, p = 0.004) and LV posterior wall thickness (from 8.7 ± 1.04mm to 10.6 ± 1.37mm, p = 0.004) in dynamics. Moreover, a smaller LV ejection fraction (LVEF) was observed in the group with an unfavorable outcome (both initially and in dynamics), as well as large LV end-diastolic volume and end-systolic volume. Single-factor analysis has shown, that EF &amp;lt;40%, LV aneurysm, the involvement of the apical LV myocardial segments at any location were echocardiography predictors of poor outcome. In the group of patients with unfavorable course of AMI, the index of left atrium (LA) increased from 35.8 ± 3.8mm to 37.3 ± 1.8mm (p = 0.04), which is significantly higher than in the second group, where the LA index was 33.8 ± 3.2mm and 34.2 ± 2.9mm (p = 0.7). In the first group, the right ventricle (RV) remained practically unchanged (22.3 ± 2.7mm and 22 ± 3.5 mm, respectively, p = 0.89), while in the second group the size of the RV decreased from 23.2 ± 3.9mm to 20.7 ± 2.9mm (p = 0.38). Initially, when comparing between groups, p = 0.38) and after 1 month p = 0.5). The negative role of pressure in the pulmonary artery (PA) in patients with AMI was also demonstrated. The systolic pressure in the PA index in the group with a favorable outcome in the dynamics significantly decreased, in contrast to the group with an unfavorable outcome (from 19.9 ± 4.5 mmHg to 16.2 ± 2.6 mmHg, p = 0.03 and from 22.1 ± 5.7mmHg to 18.0 ±3.6 mmHg, p = 0.15, respectively). Conclusion AMI with a high risk of adverse 12-month outcomes, characterized by the following echocardiographic signs: engagement apical segments of the LV regardless of the localization of myocardial infarction, reduced LVEF, as well as increased PA pressure, combined with the increase in the size of RV.

The risk of Angiotensin Converting Enzyme Inhibitor (ACEI) and Calcium Channel Blocker (CCB) used on Obstructive Sleep Apnea (OSA) incidence in hypertension patients

Abstract Background: The administration of angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) therapy is known to have a side effect of a dry cough that would trigger OSA. Further research is needed to compare the effect of these two drugs on the side effects of OSA, which could trigger high-risk patient conditions. Objective: To determine the risk of using ACE and CCB on the incidence of OSA using a case-control study method at Dau Primary Health Center. Methods: Demographic data were collected on 207 respondents aged 40-60 years by collecting Data Collection Sheets and Berlin questionnaires to determine the risk of OSA in respondents. Then, statistical analysis was carried out by determining the odds ratio (OR). Results: The results showed that one of the factors BMI (obese BMI; OR=1.33; 95% CI=0.11-15.70) induces OSA with the highest OR value compared to other factors. Conclusion: Obese patient has a 1.33 times greater risk of OSA with ACEI and CCB therapy than non-obese. It is necessary to conduct further research with a larger sample size related to OSA’s assessment associated with this therapy to improve patients’ quality of life. Keywords: Obstructive sleep apnea, ACE inhibitors, calcium channel blockers, hypertension

Hospitalization Rates in Patients with Heart Failure and Reduced Ejection Fraction Initiating Sacubitril/Valsartan or Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers: A Retrospective Cohort Study.

IntroductionThe angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (SAC/VAL) has shown benefit in patients with symptomatic heart failure (HF), including those naïve to renin–angiotensin–aldosterone system inhibitor (RAASi) therapy, and is considered the preferred RAASi for chronic HF. Real-world data on ARNI, specifically in RAASi-naïve patients, are limited. This study compared real-world outcomes of ARNI (SAC/VAL) vs. angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy in RAASi-naïve patients with HF and reduced ejection fraction (HFrEF).MethodsThis retrospective cohort study included de-identified data on RAASi-naïve patients with HFrEF (left ventricular ejection fraction ≤ 40%) who had newly initiated SAC/VAL or ACEi/ARB between July 1, 2015, and March 31, 2019, from the Optum® Electronic Health Records database in the US. New SAC/VAL users were propensity score matched 1:2 with new ACEi/ARB users by pre-selected characteristics. One-year post-index rates of all-cause, HF, and cardiovascular hospitalizations and the composite of HF hospitalization or emergency room (ER) visits were measured using negative binomial regression. Time to first all-cause hospitalization, HF hospitalization, and composite of HF hospitalization or ER visits was measured using a subdistribution hazards model.ResultsThe matched sample included 3059 new SAC/VAL and 6118 new ACEi/ARB users. Rates of all-cause hospitalization and composite of HF hospitalization or ER visits were significantly lower with SAC/VAL compared with ACEi/ARB (incidence rate ratio [95% confidence interval]: 0.87 [0.81–0.93] and 0.87 [0.81–0.94], respectively), whereas rates of HF hospitalizations and cardiovascular hospitalizations were similar (1.00 [0.91–1.11] and 0.94 [0.87–1.02], respectively). Time-to-event analyses also showed a similar trend.ConclusionsIn real-world clinical practice, RAASi-naïve patients with HFrEF initiating SAC/VAL were less likely to be hospitalized than those initiating ACEi/ARB, suggesting a potential for a reduced clinical and economic burden in these patients.

Database development and survival analysis in a clinical and historical cohort of dogs affected by myxomatous mitral valve disease treated or not with pimobendan using causal inference techniques

The aim of this work was to retrospectively evaluate the influence of pimobendan on the survival time (ST) of dogs with myxomatous mitral valve disease at different stages using an Inverse Probability Weighting (IPW) analysis. An IPW method was used to minimize confounding and IPW weighted time-repeated logistic model was used to approximate survival curves (SCs) and calculate survival differences. Subjects were allocated into exposed (E) and unexposed (U). Dogs in the American College of Veterinary Internal Medicine (ACVIM) B2 class treated with pimobendan (± ACE-inhibitors) were selected for the E group, as well as symptomatic patients (ACVIM class C) treated with triple (furosemide, ACE-inhibitor, pimobendan) or quadruple (furosemide, ACE-inhibitor, pimobendan and spironolactone) therapy. The U group included ACVIM class B2 dogs not treated with any medication and ACVIM C dogs treated with a combination of furosemide and ACE-inhibitor/spironolactone without pimobendan. The survival curve (SC) of the E group crossed the U group at 1634days. The difference between the two SCs at the time of maximum survival difference in favor of the U group was 11.3% (CI 1.7%-20.9%) (significant), in favor of the E group was 3.9% (CI -8.6%-16.4%) (not significant) and at the mean ST was 3.6% (CI -8.5%-15.7%) (not significant) in favor of the E group. For times greater than 1634days the survival was in favor of the E group, but there were no statistically significant differences in survival in favor of the E group in this clinical population.

Efficacy and Safety of Angiotensin Receptor Neprilysin Inhibitor versus Angiotensin Converting Enzyme Inhibitor in Heart Failure with Reduced Ejection Fraction- A Prospective Observational Study from a Major Tertiary Care Hospital, Assam, India

Introduction: Angiotensin Receptor Neprilysin Inhibitor (ARNI) has shown to reduce morbidity and mortality in comparison to Angiotensin Converting Enzyme Inhibitors (ACEI) inpatients of Heart Failure with Reduced Ejection Fraction (HFrEF). However, the use of ARNI in real-world practice is limited and has not been studied in North Eastern Indian population. Aim: To compare the efficacy and safety of ARNI with ACEI in the management of symptomatic chronic HFrEF in North Eastern Indian population. Materials and Methods: The prospective observational study was conducted in the Department of Cardiology at Gauhati Medical College, Guwahati, Assam, India, from April 2019 to October 2020. The study included patients with diagnosis of chronic HFrEF &lt;40%, on ACEI therapy and who had atleast one hospitalisation for Acute Decompensated Heart Failure (ADHF) in the last 6 months. A total of 63 patients were included in this study. Three patients were lost on follow-up. Out of the 60 patients who were included in the final analysis, 30 patients each were included in two groups i.e, ARNI group and ACEI group. As perdiscretion of the treating physician, the patients were started on ARNI 50 mg twice daily which consist of Sacubitril/Valsartan (24/26 mg), along with other anti-heart failure medications, and they were compared with the patients who continued on ACEI. Uptitration was considered with the aim to double the dose till the target dose was achieved at every 2-4 weeks at the treating physician’s discretion The endpoints included the rate of repeat HF hospitalisation, mortality, renal outcomes and quality of life. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS, IBM) software version 20.0. Results: The demographics and clinical characteristics were comparable between the groups. The dose of ARNI was uptitrated to a maximum of 100 mg twice daily in 11 patients. ARNI significantly reduced HF hospitalisation (36.7% vs. 66.7%; p-value=0.039) and mortality (10% vs. 20%, p-value=0.038) compared to patients with ACEI. There was a significant improvement in the KCCQ score in the ARNI group as compared to the ACEI group (p-value=0.001). Treatment with ARNI was also associated with a significant improvement in the New York Heart Association (NYHA) functional class, serum creatinine, and estimated Glomerular Filtration Rate (eGFR) and a significant reduction in N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) level. Conclusion: In patients with symptomatic HFrEF, shifting to ARNI from background therapy on ACE inhibitors in comparison with continuation of ACE inhibitors appeared to be safe and superior in reducing the risk of death and of hospitalisation, when initiated on outpatient basis. ARNI could not be uptitrated in two-third of patients, yet substantial benefits are evident even at low doses in comparison to ACE inhibitor ramipril.

IgA Crescentic Nephropathy Post COVID-19 Infection: A Case Report

Background: Since the Coronavirus Disease 2019 (COVID-19) outbreak, individuals affected by COVID19 may be at risk of acquiring certain forms of glomerular disease. Several biopsy researches reveal that acute tubular injury, as well as glomerular nephropathy were common histological findings. However, to our knowledge, there is limited data regarding de novo diagnosis of IgA vasculitis in an adult following a COVID-19 infection. Case presentation: In the present case report, we document a 24-year-old Bahraini woman with new onset hypertension, microhematuria, proteinuria and decreased renal function after she recovered from COVID-19 infection. Renal biopsy after COVID-19 infection was performed and revealed IgA nephropathy without any evidence of COVID-19 infection. After a regimen of immunosuppression and angiotensin converting enzyme inhibitor therapy, the patient recovered and remained stable upon follow-up. Conclusions: When dealing with patient with COVID-19 infection and kidney involvement, it is vital to evaluate the underlying glomerular disease aggravation as well as virus-induced consequences. A kidney biopsy may be necessary to roll out rapidly progressive glomerular disease (RPGN). Keywords: COVID-19, microscopic hematuria, IgA nephropathy, acute kidney injury, case report.