Angiotensin-converting Enzyme Inhibitors/angiotensin Receptor Blockers Research Articles

The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: real-world evidence from the CCA Database-HF Center

Abstract Background Recent clinical trials have demonstrated the potential efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNI) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction. Nevertheless, the generalizability of these findings in real-world clinical settings remains to be determined. We aimed to compare the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)on clinical outcomes in HF patients with mildly reduced or preserved ejection fraction. Methods Patient-level data was derived from the China Cardiovascular Association Database-HF Center Registry. We included exclusively a subpopulation of HF patients with left ventricular ejection fraction (LVEF) >40% and comorbid with hypertension. Patients prescripted with ARNI at discharge and sustaining to ARNI therapy during follow-up were categorized as the ARNI group, while those maintaining the usage of ACEI/ARB after discharge were designated as the ACEI/ARB group. In complete cases, the primary endpoint of all-cause mortality at one year was assessed by the 1:1 propensity score matching (PSM) method. Results In all HF patients with LVEF >40% comorbid with hypertension, the usage of ARNI has increased from 0.9% in 2017 to 37.2% in 2021. A total of 3348 patients in the ARNI group and 7688 patients in the ACEI/ARB group were identified for comparative effectiveness. After 1:1 PSM, 5482 patients were included in the primary analysis, with 2741 patients in each treatment arm. The proportion of patients receiving higher dosages of ARNI (200mg/d and 400mg/d) was 20.9%, 26.6%, 29.2%, and 30.3% at discharge, 1-month, 3-month, and 1-year, respectively. Over the 1-year follow-up, ARNI was associated with a 20% relative reduction in all-cause death compared to the ACEI/ARB therapy (10.5% vs. 12.9%, adjusted hazard ratio [HR], 0.80 [95% CI, 0.69-0.94], P=0.005). The absolute risk difference in all-cause death between ARNI and ACEI/ARB arms was 2.88 per 100 patient-years (incidence rate difference, -2.88 [95% CI, -4.86 to -0.9]). Cardiovascular death also tended to decrease in the ARNI group but with missed statistical significance (4.5% vs. 4.9%, adjusted HR, 0.89 [95% CI, 0.70-1.14], P=0.373). Treatment benefits were more significant in those with LVEF between 40-50% (adjusted HR, 0.62 [95% CI, 0.48-0.79]), 50-60% (adjusted HR, 0.85 [95% CI, 0.68-1.06]), but not observed in HF patients with LVEF>60% (adjusted HR, 1.80 [95% CI, 1.08-2.98]; Pinteraction<0.001). Conclusion In real-world clinical settings, treatment with ARNI was associated with a significant relative risk reduction in all-cause mortality compared with ACEI/ARB in HF patients with mildly reduced or preserved LVEF. The cardiovascular benefit was concentrated in patients with LVEF ≤60%.

Prevalence of Chronic Obstructive Pulmonary Disease Exacerbation with Heart Failure Comorbid: A Systematic Review and Meta-Analysis

Heart Failure (HF) is one of the comorbidities in Chronic Obstructive Pulmonary Disease (COPD), associated with the incidence of respiratory tract infections which is a risk factor for COPD exacerbations. Eleven studies conducted in the meta-analysis. Pooled prevalence of COPD exacerbations with HF comorbidity was 29,43 % (95%CI:17,68%- 42,92%) and statistical heterogenity among the eleven studies was significant (I2 = 99,95%. Q = 191,96 p=<0,001). Eight studies were based in Europe, two studies in Americas and one study in Asia. Prevalence of COPD exacerbations with HF comorbidity based on WHO region subgroup analysis found European region 31,44% (95%CI: 17,87%-46,58%), America’s region 32,92% (95%CI: 12,61%-55,73%) and the Western Pacific region 10,86% (95%CI:10,03%- 13,21%) with significant statistical heterogeneity (I2 = 99,94%, Q = 191,96, p= <0,001). The age of exacerbating COPD patients with comorbid heart failure was above 70 years and there were differences in gender characteristics based on the two studies that reported. Statins reduce the incidence of COPD exacerbations. Differences in the risk of COPD exacerbation receiving Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker (ACEi/ARB) therapy. The most common comorbid cardiovascular disease apart from heart failure are atrial fibrillation and ischemic heart disease. As a conclusion, the pooled prevalence of COPD exacerbations with heart failure comorbid in this systematic review and meta-analysis was 29.43% (95% CI:17.68%-42.92%). Keywords: COPD exacerbation, Heart Failure, prevalence

The use of sodium-glucose cotransporter type 2 inhibitors for the treatment of chronic heart failure in cancer patients receiving cardiotoxic chemotherapy. Preliminary results.

Background. Chronic heart failure (CHF) is one of the most serious and late manifestations of cardiotoxicity during treatment with antitumor drugs in cancer patients. As of today, only 2 groups of drugs have proven significant cardioprotective effects in this category of patients: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and beta-blockers (BABs). Only recently has data emerged on the successful use of sodium-glucose cotransporter type 2 inhibitors (SGLT-2) in patients with CHF on anthracycline therapy.Aim. To evaluate the role of SGLT-2 inhibitors in the complex treatment of CHF in cancer patients receiving cardiotoxic chemotherapy.Methods. A prospective observational open study, including 60 patients with verified CHF who received cardiotoxic chemotherapy and dual cardioprotective therapy: ACEIs/ARBs + BABs (control group); and 56 patients who receive similar therapy with the addition of Dapagliflozin 10 mg 1 time in the morning (study group). The results were monitored after 6 months using laboratory and instrumental research methods, as well as additional control methods. Results. Troponin T, N-terminal prohormone of brain natriuretic peptide (NTproBNP) and left ventricular longitudinal strain (GLS) levels were compared in 47 patients who had completed all follow-up studies at 6 months. It was noted that the dynamics of troponin in both groups did not differ significantly (p0.753 and p0.260, respectively), and the level of NTproBNP significantly decreased in the study group by 7.8% compared to the control group (p0.006). Comparable data were obtained for GLS (a decrease in the study group by 6.5% in relative values) compared to the control group (p0.008)). 22 (46.8%) patients had CHF before the start of chemotherapy, and in 25 (53.2%) CHF arose during antitumor drug therapy. There were 17 (16%) deaths, but there were no deaths from heart failureinbothgroups.Conclusion. We believe that a decrease in the marker of heart failure and a less pronounced impairment of the longitudinal deformation of the left ventricle with the addition of SGLT-2 inhibitors to the basic therapy of CHF in cancer patients receiving cardiotoxic chemotherapy can slow down the progression of CHF.

Unveiling the Landscape of Acute Kidney Injury in Surgical Patients: A Systematic Review of Risk Factors and Clinical Biomarkers

Acute Kidney Injury (AKI) is a critical complication with significant implications for surgical patients, leading to increased morbidity, mortality, and healthcare costs. Identifying the risk factors and clinical biomarkers associated with AKI in the surgical context is essential for timely intervention and personalized management. To address this knowledge gap, we conducted a systematic review to comprehensively analyze existing literature on AKI in surgical patients. In this paper, we provided a systemically review analysis based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) technique for AKI risk factors and clinical biomarkers. The advanced searching into two powerful databases which is Scopus, Pubmed and Mendeley. Based on searching, find finally main data n=30 and will be analyzed using the synthesis approach. Through a meticulous search and appraisal of studies in reputable scientific databases, we identified a diverse range of research articles, clinical trials, and cohort studies that met our rigorous inclusion criteria. Synthesizing the findings from these studies, we explored the multifactorial nature of AKI, encompassing patient-related factors, surgical variables, and exposure to potential nephrotoxic agents. Our review revealed that AKI in surgical patients is influenced by a complex interplay of risk factors, including patient demographics, comorbidities, surgical procedures, anaesthetic management, and exposure to nephrotoxic drugs. The systematic analysis identified the most common drug classes associated with drug-induced AKI, such as diuretics, ACE inhibitors/angiotensin receptor blockers (ACEIs/ARBs), and antibiotics

Outcome of COVID-19 infection in patients on antihypertensives: A cross-sectional study.

Patients with coronavirus disease 2019 (COVID-19) infection frequently have hypertension as a co-morbidity, which is linked to adverse outcomes. Antihypertensives may affect the outcome of COVID-19 infection. To assess the effects of antihypertensive agents on the outcomes of COVID-19 infection. A total of 260 patients were included, and their demographic data and clinical profile were documented. The patients were categorized into nonhypertensive, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), calcium channel blocker (CCB), a combination of ACEI/ARB and CCB, and beta-blocker groups. Biochemical, hematological, and inflammatory markers were measured. The severity of infection, intensive care unit (ICU) intervention, and outcome were recorded. The mean age of patients was approximately 60-years-old in all groups, except the nonhypertensive group. Men were predominant in all groups. Fever was the most common presenting symptom. Acute respiratory distress syndrome was the most common complication, and was mostly found in the CCB group. Critical cases, ICU intervention, and mortality were also higher in the CCB group. Multivariable logistic regression analysis revealed that age, duration of antihypertensive therapy, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and interleukin 6 were significantly associated with mortality. The duration of antihypertensive therapy exhibited a sensitivity of 70.8% and specificity of 55.7%, with a cut-off value of 4.5 years and an area under the curve of 0.670 (0.574-0.767; 95% confidence interval) for COVID-19 outcome. The type of antihypertensive medication has no impact on the clinical sequence or mortality of patients with COVID-19 infection. However, the duration of antihypertensive therapy is associated with poor outcomes.

Analysis of Longitudinal Patterns and Predictors of Medicine Use in Residential Aged Care Using Group-Based Trajectory Modeling: The "MEDTRAC-Cardiovascular" Longitudinal Cohort Study.

Cardiovascular diseases are the leading cause of death globally. Ensuring ongoing use of medicines-medication persistence-is crucial, yet no prior studies have examined this in residential aged care facilities (RACFs). We aimed to identify long-term trajectories of persistence with cardiovascular medicines and determine predictors of persistence trajectories. A longitudinal cohort study of 2837 newly admitted permanent residents from 30 RACFs in New South Wales, Australia. We monitored weekly exposure to six cardiovascular medicine classes-lipid modifiers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs), beta-blockers, diuretics, calcium channel blockers (CCB), and cardiac therapy-over 3 years. Group-based trajectory modeling was employed to determine persistence trajectories for each class. At baseline, 76.6% (n = 2172) received at least one cardiovascular medicine with 41.2% receiving lipid modifiers, 31.4% ACEI/ARBs, 30.2% beta-blockers, 24.4% diuretics, 18.7% CCBs, and 14.8% cardiac therapy. The model identified two persistence trajectories for CCBs and three trajectories for all other classes. Sustained high persistence rates ranged from 68.4% (ACEI/ARBs) to 79.8% (beta-blockers) while early decline in persistence and subsequent discontinuation rates ranged from 7.6% (cardiac therapy) to 25.3% (CCBs). Logistic regressions identified 11 predictors of a declining persistence across the six medicine classes. Our study revealed varied patterns of cardiovascular medicine use in RACFs, with 2-3 distinctive medicine use trajectories across different classes, each exhibiting a unique clinical profile, and up to a quarter of residents discontinuing a medicine class. Future studies should explore the underlying reasons and appropriateness of nonpersistence to aid in identifying areas for improvement.

Real-world experience of angiotensin receptor-neprilysin inhibitors in patients with heart failure and dialysis.

Although angiotensin receptor-neprilysin inhibitor (ARNI) has shown promise in patients with heart failure and reduced ejection fraction (HFrEF), the treatment effect in HFrEF patients with end-stage renal disease (ESRD) undergoing dialysis is uncertain. This study aimed to examine the real-world effects of ARNI vs. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in this subpopulation. This multi-institutional, retrospective study identified 349 HFrEF patients with ESRD on dialysis, who initiated either ARNI or ACEI/ARB therapy. Efficacy outcomes included rates of hospitalization for heart failure (HHF) and mortality, as well as changes in echocardiographic parameters. Safety outcomes encompassed hypotension and hyperkalemia. Treatment effects were assessed using Cox proportional hazards models, with additional sensitivity analyses for robustness. Out of 349 patients screened, 89 were included in the final analysis (42 in the ARNI group and 47 in the ACEI/ARB group). After 1 year of treatment, echocardiographic measures between the two groups were comparable. The primary composite rate of HHF or mortality was 20.6 events per 100 patient-years in the ARNI group and 26.1 in the ACEI/ARB group; the adjusted hazard ratio was 0.98 (95% CI: 0.28-3.43, P = 0.97). Their safety outcomes did not differ significantly. Sensitivity analyses, including repetitive sampling, propensity score matching, and extended follow-up, corroborated these findings. ARNI has proven effective in treating HFrEF patients; however, significant benefits were not observed in these patients with ESRD undergoing dialysis compared with ACEI/ARB in this real-world cohort. Future research employing a more extended follow-up period, larger sample size, or randomized design is warranted to investigate the treatment effects in this subpopulation.

Tricuspid Regurgitation Stratification Predicts the Time Course of Systemic Right Ventricle Dysfunction Among Patients on ACE-I/ARB

BackgroundProgressive systemic right ventricle (sRV) dysfunction is a significant challenge in adult congenital heart disease. Current guidelines do not specify effective heart failure medications for patients with sRV; however, previous studies have relied on semiquantitative assessments. The advancement of cardiac magnetic resonance (CMR) imaging as the gold-standard modality offers quantitatively accurate assessments even for complex cardiac anomalies. Therefore, we aimed to investigate prognostic factors associated with sRV dysfunction in patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE-I/ARB), using CMR-derived quantitative values. MethodsWe conducted a retrospective cohort study of 17 adult patients with sRV treated with ACE-I/ARB and performed logistic regression analysis, with the primary outcome defined as sRV ejection fraction (sRVEF) deterioration. ResultsOver an average follow-up period of 68.7 months, sRVEF deterioration occurred in 3 patients (17%). Logistic regression analysis identified tricuspid regurgitation (TR) as a potential independent prognostic factor for the primary outcome (odds ratio = 1.11; 95% confidence interval, 1.00-1.31). Furthermore, patients with mild TR (TR fraction ≤15%; N = 12) experienced improvements in sRVEF between the initial and last CMR assessments (from 49.1% ± 8.4% to 56.7% ± 8.0%, P = 0.0029), with increased stroke volume from 68.2 ± 18.6 to 79.5 ± 17.2 mL (P = 0.0029). In contrast, these changes were not observed in patients with moderate or severe TR (TR fraction >16%) (N = 5). ConclusionsOur CMR-based evaluation highlights the potential utility of TR stratification in predicting the changes in sRVEF among patients with sRV on ACE-I/ARB. Future randomized controlled trials that consider TR severity are required to elucidate the significance of ACE-I/ARB therapy.

Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers After Coronary Artery Bypass Graft Surgery: A Population-Based Cohort Study.

The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) on major adverse cardiovascular events (MACE) in patients who undergo coronary artery bypass graft surgery is equivocal. This retrospective, population-based cohort study evaluated effect of exposure to an ACEI/ARB on MACE using linked administrative databases that included all cardiac revascularization procedures, hospitalizations, and prescriptions for the population of British Columbia, Canada. All adults who underwent coronary artery bypass graft surgery between 2002 and 2020 were eligible. The primary outcome was time to MACE, defined as a composite of all-cause death, myocardial infarction, and ischemic stroke using Cox proportional hazards models with inverse probability treatment weighting. Included were 15 439 patients and 6191 (40%) were prescribed an ACEI/ARB. Mean age was 66 years, 83% were men, and 16% had heart failure (HF). Median exposure time was 40 months. Over the 5-year follow-up, 1623 MACE occurred. Impact of exposure was different for patients with and without HF (P <0.0001 for interaction). After probability-weighting and adjustment for relevant covariates, exposure to ACEI/ARBs was associated with a lower hazard of MACE in patients with HF at 1 year (hazard ratio, 0.13 [95% CI, 0.09-0.19]) and 5 years (hazard ratio, 0.36 [95% CI, 0.30-0.44]). In patients without HF, ACEI/ARBs had a lower hazard of MACE at 1 year (hazard ratio, 0.35 [95% CI, 0.27-0.46]) and 5 years (hazard ratio, 0.66 [95% CI, 0.58-0.76]). In this population-based study, ACEI/ARBs were associated with a lower hazard of MACE in a cohort of patients post-coronary artery bypass graft surgery irrespective of HF status.

Efficacy and Safety of Sacubitril/Valsartan in Adverse Cardiovascular Event Reduction and Hypertension Control Among Asians: A Systematic Review and Meta-analysis of Randomized Controlled Trials

BACKGROUND: Sacubitril/valsartan is currently a standard medication in the treatment of reduced ejection fraction heart failure (HFrEF), and studies have also shown its efficacy for controlling hypertension. However, its efficacy varies between populations, and current recommendations are predominantly based on non-Asian data. Hence, this study synthesizes the available evidence to determine its overall efficacy and safety among Asians. METHODS: A systematic search through PubMed, ScienceDirect, Cochrane, HERDIN PLUS, and ClinicalTrials.gov was done to include randomized controlled trials with Asian data comparing sacubitril/valsartan against an active control. The Cochrane Risk of Bias 2.0 was used to assess each article for bias. Forest plots in fixed-effects model for major adverse cardiovascular events (MACEs), hypertension control, and safety were created using RevMan 5.4. RESULTS AND DISCUSSION: Ten articles with an overall low risk of bias were included involving 6120 Asians. Sacubitril/valsartan showed better hypertension control against conventional angiotensin blocker (odds ratio [OR], 1.63; confidence interval [CI], 1.38–1.92; I2 = 7%). However, MACE reduction was not significant in HFrEF (hazard ratio, 0.89; CI, 0.73– 1.08; I2 = 0%) or acute myocardial infarction (hazard ratio, 0.90; CI, 0.65–1.24; I2 = 0%). Safety was comparable to conventional angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ARB) with a severe adverse event OR of 0.81 (CI, 0.44–1.50; I2 = 38%) and nonsevere adverse event OR of 1.09 (CI, 0.88–1.35; I2 = 44%). These results implicate the need for efficacy studies focused on Asians, reassessment of the strength of recommendations in the treatment of heart failure, and consideration of sacubitril/valsartan as a treatment option for hypertension. CONCLUSION: Among Asians, better hypertension control is seen with LCZ696 than conventional ARB. However, MACE reduction in HFrEF or acute myocardial infarction is insignificant, although there is a trend toward benefit. Finally, safety is comparable to conventional angiotensin-converting enzyme inhibitors/ARBs. KEYWORDS: acute myocardial infarction, Asians, heart failure, hypertension, LCZ696, sacubitril/ valsartan

Differences in provider approach to initiating and titrating guideline directed medical therapy in heart failure with reduced ejection fraction

BackgroundDespite the strong evidence supporting guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), prescription rates in clinical practice are still lacking.MethodsA survey containing 20 clinical vignettes of patients with HFrEF was answered by a national sample of 127 cardiologists and 68 internal/family medicine physicians. Each vignette had 4–5 options for adjusting GDMT and the option to make no medication changes. Survey respondents could only select one option. For analysis, responses were dichotomized to the answer of interest.ResultsCardiologists were more likely to make GDMT changes than general medicine physicians (91.8% vs. 82.0%; OR 1.84 [1.07–3.19]; p = 0.020). Cardiologists were more likely to initiate beta-blockers (46.3% vs. 32.0%; OR 2.38 [1.18–4.81], p = 0.016), angiotensin receptor blocker/neprilysin inhibitor (ARNI) (63.8% vs. 48.1%; OR 1.76 [1.01–3.09], p = 0.047), and hydralazine and isosorbide dinitrate (HYD/ISDN) (38.2% vs. 23.7%; OR 2.47 [1.48–4.12], p < 0.001) compared to general medicine physicians. No differences were found in initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARBs), initiating mineralocorticoid receptor antagonist (MRA), sodium-glucose transporter protein 2 (SGLT2) inhibitors, digoxin, or ivabradine.ConclusionsOur results demonstrate cardiologists were more likely to adjust GDMT than general medicine physicians. Future focus on improving GDMT prescribing should target providers other than cardiologists to improve care in patients with HFrEF.

Beta blockers are associated with lower all-cause mortality among HFpEF patients.

The evidence regarding beta blocker (BB) benefit in heart failure with preserved ejection fraction (HFpEF) remains inconclusive, leading to consideration of BB withdrawal in this population. In this study, we retrospectively analyzed the association of BB on all-cause mortality in HFpEF patients. This is a single-center retrospective cohort study of 20,206 patients with left ventricular ejection fraction (EF) ≥ 50% who were hospitalized with decompensated HF between January 2011 and March 2020. Survival is reported at 30days, 1year, and 3years. A secondary analysis comparing mortality for patients on BB with additional indications including hypertension (HTN), coronary artery disease (CAD), and atrial fibrillation (AF) was completed. Mortality was compared between patients on BB and additional therapies of spironolactone or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs). BB showed lower all-cause mortality at 30days, 1year, and 3years (p < 0.0001). This association with lower all-cause mortality was validated by a supplementary propensity score-matched analysis. At 3years, there was significant mortality reduction with addition of BB to either spironolactone (p = 0.0359) or ACEi/ARBs (p < 0.0001). In a large single-center retrospective registry, BB use was associated with lower mortality in HFpEF patients with a recent decompensated HF hospitalization. The mortality benefit persisted in those treated with spironolactone or ACEi/ARBs, and in those with AF. This provocative data further highlights the uncertainty of the benefit of BB use in this cohort and calls for re-consideration of BB withdrawal, especially in those tolerating it well, without conclusive, large, and randomized trials showing lack of benefit or harm.

Association between critical care admission and chronic medication discontinuation post-hospital discharge: A retrospective cohort study.

Background: Discontinuation of important chronic medication after hospitalisation is common. This study aimed to investigate the association between critical care (vs non-critical care) admission and discontinuation of chronic medications post-hospital discharge, along with factors associated with discontinuation among critical care survivors. Methods: This was a retrospective cohort study in Lothian, Scotland of adults who were admitted to hospital between 01/01/2012 and 31/12/2019 and survived to hospital discharge. Medication classes investigated were statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs), beta-blockers, oral anticoagulants, and thyroid hormones. The risk of medication discontinuation for each class was estimated by odds ratios (OR), with 95% confidence intervals (95%CI), using multivariable logistic regression adjusted for patient demographics, main clinical condition, and index comorbidity. A secondary analysis assessed factors associated with discontinuation in critical care survivors. Results: There were 22,340 critical care and 367,185 non-critical care survivors included. Critical care admission had the highest association with ACEi/ARBs discontinuation (adjusted OR 2.41, 95%CI: 2.26-2.58), followed by oral anticoagulants (adjusted OR 1.33, 95%CI: 1.15-1.53), and beta blockers (adjusted OR 1.18, 95%CI: 1.07-1.29). There was no significant association with thyroid hormones or statin discontinuation. Among critical care survivors, hospital length of stay of 14 days or more was associated with increased discontinuation across all medication classes. Conclusion: Critical care admission was associated with discontinuation of three out of five medication classes studied (ACEi/ARBs, beta-blockers, and oral anticoagulants). Further research is needed to understand the reason for increased medication discontinuation in critical care survivors and how these risks can be mitigated to improve patient outcomes.

Variability in guideline-directed medical therapy across sites and operators and long-term mortality and amputation outcomes risk in patients undergoing peripheral vascular interventions

The use of guideline-directed medical therapy (GDMT) in patients undergoing peripheral vascular interventions (PVIs) decreases the risk of death and amputation and may decrease hospital readmissions. The variability of GDMT prescription across sites and operators and the proportionality of risk is not well understood. We aimed to study the association between variability of GDMT prescription at the site and operator level and outcomes (including 90-day readmissions and 24-month all-cause mortality and major amputation). We examined GDMT discharge rates in PVIs performed between 2017 and 2018 using Medicare-linked Vascular Quality Initiative registry. GDMT included a statin, antiplatelet therapy, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-i/ARB) if hypertensive. Quartiles (Q1-4) of GDMT rates were documented by operators and sites and variability was quantified using median odds ratios (MOR) and intraclass correlation (ICC). The association between lower GDMT rates (per 10%) by sites and operators with 90-day readmission were calculated using logistic regression, and with 24-month mortality and major amputation using parametric survival model. Models were adjusted for patient-level factors and included sites and operators nested within sites as 2 random effects. GDMT rates for 17,147 patients across 223 sites and 1,263 operators ranged from 0% to 38% (Q1, MOR 1.43, 95%CI 1.39-1.47, P ≤ .001) to 57%-100% (Q4, MOR 1.48, 95%CI 1.44-1.51, P ≤ .001). Four percent of variance in GDMT use was explained by sites (ICC 3.9, 95%CI 2.9-5.3) and operators (ICC 4.1, 95%CI 3.1-5.4). A dose-response relationship was noted between lower GDMT rates and increased risk of 90-day readmission risk by sites (P = .021) and operators (P < .001). Lower GDMT prescription by site was associated with higher risk of 24-month mortality (HR = 1.07, 95%CI 1.02-1.13) and major amputation (HR = 1.08, 95%CI 1.01-1.15). Similar associations were found for GDMT use by provider (mortality HR = 1.05, 95%CI 1.02-1.08 and amputation HR = 1.04, 95%CI 1.00-1.08). Both at the operator and health system level, there was significant variability in GDMT prescription following PVI, proportionally translating into risk for readmission, mortality, and major amputation. Targeted quality efforts should prioritize both operator and site levels to improve GDMT use and outcomes for patients undergoing PVI.

Add-on Sacubitril/Valsartan Therapy Induces Left Ventricular Remodeling in Non-responders to Cardiac Resynchronization Therapy to a Similar Extent as in Heart Failure Patients Without Resynchronization.

Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy. CRT-NR patients initiated on SV (groupI), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (groupII), and patients with HFrEF (without CRT) initiated on SV (groupIII) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared. A total of 275 patients (groupI, 70; groupII, 70; and groupIII, 135) were included. After a follow-up of 7.54 ± 1.8months (mean ± standard deviation [SD]), LV EF (%) increased in groupI (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in groupIII (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in groupI (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in groupIII (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in groupI (2058.86 [1041.07-4502.51] versus 1121.55 [545-2541]; p < 0.001) and in groupIII (2223.35 [1233.03-4795.96] versus 1123.09 [500.38-2651.27]; p < 0.001). The extent of improvement was similar in groupsI and III (p > 0.05). No significant changes were detected in groupII. SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.

Efficacy and safety of mineralocorticoid receptor antagonists for the treatment of low-renin hypertension: a systematic review and meta-analysis

Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by −6.8 mmHg (95% confidence interval −9.6 to −4.1) and −4.8 mmHg (95% confidence interval −11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.

Prevalence, Risk Factors, and Mortality of Patients Presenting with Moderate and Severe Hyponatremia in Emergency Departments.

Hyponatremia is among the most common electrolyte disturbances encountered in clinical practice and is associated with a high rate of morbidity and mortality. However, there are very limited data on adult cases presenting to emergency departments with hyponatremia. This study aimed to evaluate the frequency, clinical characteristics, and outcomes in hyponatremic patients presenting to emergency departments. This retrospective study analyzed all patients older than 18 years who visited our institution's emergency department between October 2018 and October 2019 and has a serum sodium (Na) level <130 mmol/L. Among 24,982 patients who visited the emergency department and had a documented serum sodium level, 284 were included. Patients' median age was 67.13 ± 14.8 years. Younger patients are less likely to develop severe hyponatremia compared to older patients (adjusted odds ratio (AOR): 0.415; 95% confidence interval (CI): 0.231-0.743; p=0.003). Asymptomatic hyponatremia and gastrointestinal manifestations were the most common presenting hyponatremia symptoms (33.7% and 24.2%, respectively). Proton pump inhibitor (PPI) use, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE/ARB) use, and spironolactone use (OR = 2.6 and 3.9, 2.3 with a p=0.02, 0.03, and 0.05, respectively) were associated with increased odds of severe hyponatremia. There is no difference in the overall mortality rate within 6 months of presentation between severe and moderate hyponatremia groups (11.1% versus 16.2%, p=0.163). Moderate and severe hyponatremia are not uncommon among patients presenting to emergency departments. Moderate hyponatremia can be asymptomatic with clinical significance. Older patients, use of PPI, use of ACEi/ARBs, and spironolactone use were associated with an increased risk of severe hyponatremia compared to moderate. Further prospective analysis of a larger population is needed to confirm our findings.

A diabetes registrar assisted workflow intervention in general practice for systematic initiation of cardiorenal medications for patients with type 2 diabetes and albuminuria in Aotearoa New Zealand.

To evaluate whether a weekly diabetes registrar clinic and case discussions conducted over 12 weeks in primary care improves guideline management of type 2 diabetes (T2D). A registrar-led diabetes clinic was incorporated into two primary care practices in Tāmaki Makaurau Auckland for 3 months. Patients with T2D and albuminuria appearing on practice dashboards as not prescribed angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB), or sodium-glucose cotransporter-2 inhibitor/glucagon-like peptide-1 receptor agonist (SGLT2i/GLP1RA) were booked into these clinics. Opportunistic education sessions were provided by the diabetes registrar and prescribers were surveyed to understand the challenges in management of T2D. Of 125 patients booked, 80 attended the registrar clinic. Of these, 68% were clinically suitable for SGLT2i/GLP1RA and 8% for ACEi/ARB. SGLT2i/GLP1RA were initiated in 92% and ACEi/ARB in 89% of eligible patients. Two patients had contraindications for SGLT2i/GLP1RA, and one patient declined both. Additional cardiorenal medications were initiated in 16% of patients. Survey responses of 12 prescribers indicated acute illness takes priority over diabetes management, and lack of time and knowledge are main barriers to optimising diabetes care. A visiting diabetes registrar intervention was successful in initiating guideline medications for T2D in primary care. It remains to be evaluated whether this leads to practice-wide improvements in prescribing gaps in the short or longer term.

Trajectories of adherence to ACEI/ARB medications following a motivational interviewing intervention among Medicare Advantage beneficiaries in Texas

ObjectivesTo assess the impact of student telephone motivational interviewing intervention on angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARBs) adherence trajectories and identify predictors of each trajectory. MethodsThe intervention group included continuously enrolled Medicare Advantage Plan patients non-adherent to ACEI/ARBs vs the control group (1:2 ratio). The intervention was tailored by pre-intervention trajectories and included an initial and five follow-up calls. Adherence was measured 6 months after initial calls using the proportion of days covered (PDC). Monthly PDCs were integrated into a group-based trajectory model and categorized patients into 4-groups. A multinomial logistic regression model was used to evaluate trajectory predictors. ResultsThe study comprised 240 intervention patients and 480 controls with four trajectories: adherent trajectory 44.2%, gradual improvement in adherence 13.4%, slow decline in adherence 24.1%, and discontinuation 18.3%. Patients with the intervention were less likely to experience a slow decline in adherence than controls (OR: 0.627 [0.401–0.981]). Patients with specialty prescribers’ visits, ≥ 1 previous hospitalization, rapid decline in adherence as pre-intervention trajectory, and higher CMS risk score were associated with discontinuation trajectory. ConclusionIntervention patients vs controls had a lower likelihood of following a slow decline in adherence pattern. Practice implicationsThis study underscores the importance of individualized interventions and the association between past adherence patterns and post-intervention trajectories.

Timing of angiotensin receptor-neprilysin inhibitor initiation in patients with heart failure and reduced ejection fraction: data from the Swedish heart failure registry

Abstract Background International guidelines recommend early and fast optimization of the treatments for heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilyisin inhibitor (ARNI) reduced mortality/morbidity in HFrEF. However, despite early initiation of ARNI appeared safe and of potential benefit in randomized clinical trials, their early implementation is underutilized in real world. Purpose To explore the timing, modalities and predictors of ARNI initiation in a large, nationwide cohort of patients with HFrEF. Methods ARNI-naïve patients with HFrEF (EF&amp;lt;40%) registered in the SwedeHF Registry from January 2017 to December-2021 were included. Separate analyses were performed to investigate ARNI initiation in terms of 1) course of the disease (duration of HF &amp;lt;6 vs ≥6 months), 2) location (in hospital vs out-patient), 3) time from a previous HF hospitalization (in-hospital or ≤14 days from discharge vs 15-90 days vs &amp;gt;90 days or no initiation). Results Analysis 1) Among 16,086 HFrEF patients registered in SwedeHF during the study period, 63% had an HF duration &amp;lt;6 months. 5% vs. 9% of patients with HF duration &amp;lt;6 vs. ≥6 initiated ARNI, respectively. Younger age and referral to specialty care were more strongly associated with ARNI initiation whether HF duration was ≥6 or &amp;lt;6 months. In-patient status, lower EF, and hypertension were independently associated with initiation only if HF duration was &amp;lt;6 months, and HF nurse-led clinic and higher income only if HF duration was ≥6 months. Previous ACEi/ARB use was associated with more likely ARNI initiation in HF duration ≥6 months and less likely initiation in HF duration &amp;lt;6 months (Figure). Analysis 2) Of 1,065 HFrEF patients who initiated ARNI, 30% started as in-patients. Analysis 3) Among 3,892 patients registered as in-patients in SwedeHF, 8% initiated ARNI ≤14 days from the hospital discharge, 4% between 15-90 days, and 88% &amp;gt;90 days or did not initiate. Important independent predictors of earlier initiation (≤14 days) were a more recent registration in SwedeHF, follow-up in specialty care and HF nurse-led clinic, lower EF, worse New York Heart Association class, previous use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB), use of mineralocorticoid receptor antagonist, ICD/CRT, and higher income, whereas older age, higher mean arterial pressure, atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD), and living alone where associated with lower likelihood. Conclusions In this nationwide HFrEF cohort ARNI were rarely initiated early at/after an HF hospitalization discharge, initiation was more likely in the out-patient setting and in the later course of the HF disease. Key patient characteristics associated with early initiation were linked with more severe HF and follow-up in dedicated HF care. Overall our data highlight a delayed initiation of ARNI therapy and claim for better implementation in the early stage of HF.Predictors of ARNI initiation