When Revascularization May Be Appropriate in Atherosclerotic Renal Artery Stenosis.

Renal artery stenosis (RAS) is a condition that involves the narrowing of one or both renal arteries, most commonly caused by either atherosclerosis or fibroplasia. RAS can present in a multitude of clinical manifestations involving hypertension (HTN), heart failure, and renal failure. Current recommendations for treating patients with RAS involve strict medical therapy often without invasive therapies. However, in more complicated patients with RAS, recent clinical studies and guidelines have offered varying recommendations, which has presented challenges in managing these cases. This review aims to summarize current evidence to best evaluate which patients with RAS may benefit from renal artery revascularization as opposed to medical therapy alone.

Sacubitril/Valsartan Versus Enalapril in Chronic Chagas Cardiomyopathy: Rationale and Design of the PARACHUTE-HF Trial.

Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF. The study aims to enroll approximately 900 patients with CCC and reduced ejection fraction at around 100 sites in Latin America. The primary outcome is a hierarchical composite of time from randomization to cardiovascular death, first HF hospitalization, or relative change from baseline to week 12 in NT-proBNP levels. PARACHUTE-HF will provide new data on the treatment of this high-risk population. (Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC [PARACHUTE-HF]; NCT04023227).

Exploring the Molecular Underpinnings of Skin Regeneration and Wound Healing: The Role of Renin Angiotensin.

The aim of this study is to review the role of renin-angiotensin in skin regeneration and wound healing with a focus on molecular mechanisms. Angiotensin receptor type 1 (AT1R) are abundant in the wounded area, and thus, lead to the activation of ERK, STAT1, and STAT3 which can lead to epidermal self-renewal. The expression of Renin Angiotensin System (RAS) components was significantly lower in wounds caused by burning, rather than intact skin, noting that RAS is involved in the re-epithelialization of skin. ERK, STAT and STAT3 are the targets of Ang II, indicating that RAS active components are involved in fibroblast, stem cells and keratinocyte migration. The effect of inhibiting the RAS on wound healing is context-dependent. On one hand, it is suggested that inhibiting RAS during this phase may slow down wound healing speed. On the other hand, studies have shown that RAS inhibition in this phase can lead to α-SMA activation, ultimately accelerating the wound healing process. Most of the investigations indicate that the inhibition of RAS with Angiotensin Receptor Blockers (ARBs) and Angiotensin Converting Enzyme (ACE) plays a significant role in tissue remodeling in the last phase of wound healing. It has been shown that the inhibition of RAS can inhibit scar formation and fibrosis through the downregulation of inflammatory and fibrogenic agents, such as TGF-ß, SMAD2/3, and TAK1, PDGF-BB, and HSP47. To sum up, that local administration of RAS regulators might lead to less scar formation and inflammation in the last phase of wound closure.

PHARMACOGENETICS OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI) AND ANGIOTENSIN II RECEPTOR BLOCKERS (ARB) IN CARDIOVASCULAR DISEASES.

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

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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

Hyponatremia in geriatric patients.

Hyponatremia is the most frequent electrolyte imbalance in geriatric medicine. Causes of hyponatremia were retrospectively analyzed in all in-patients treated in 2016 (N = 2267, 1564 women, 703 men, mean age ± standard deviation 81.9 ± 7.6 years). Any form of hyponatremia on admission, during the stay or on discharge was noted in 308 patients (13.6%, 231 women, 77 men; mean age ± standard deviation 83.1 ± 7.3 years, p = 0.009 vs. age of all patients). Women had a higher probability of developing hyponatremia compared to men (p = 0.019), 131 patients were hypovolemic, and dyspnea as an indicator of hypervolemia was noted in 71 patients.Only 12 patients suffering from hyponatremia (3.9%) did not receive any of the potentially sodium-lowering drugs assessed (diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, antidepressants, neuroleptics, nonsteroidal antirheumatics, carbamazepine, oxcarbazepine). The median number of drugs per patient potentially lowering the plasma sodium level was 3 and the maximum number was 7.Hypovolemic hyponatremia and the syndrome of inadequate antidiuretic hormone secretion were the most important causes of hyponatremia. Adverse drug effects were the main origins of both conditions. In patients with hyponatremia the drug load influencing plasma sodium level should be minimized, thiazide diuretics should be avoided and older individuals should receive a diet with sufficient salt content.

Lisinopril increases lung ACE2 levels and SARS-CoV-2 viral load and decreases inflammation but not disease severity in experimental COVID-19.

COVID-19 causes more severe and frequently fatal disease in patients with pre-existing comorbidities such as hypertension and heart disease. SARS-CoV-2 virus enters host cells through the angiotensin-converting enzyme 2 (ACE2), which is fundamental in maintaining arterial pressure through the renin-angiotensin system (RAS). Hypertensive patients commonly use medications such as angiotensin-converting enzyme inhibitors (ACEi), which can modulate the expression of ACE2 and, therefore, potentially impact the susceptibility and severity of SARS-CoV-2 infection. Here we assessed whether treatment of ACE2-humanized (K18-hACE2) mice with the ACEi Lisinopril affects lung ACE2 levels and the outcome of experimental COVID-19. K18-hACE2 mice were treated for 21 days with Lisinopril 10 mg/kg and were then infected with 105 PFU of SARS-CoV-2 (Wuhan strain). Body weight, clinical score, respiratory function, survival, lung ACE2 levels, viral load, lung histology, and cytokine (IL-6, IL-33, and TNF-α) levels were assessed. Mice treated with Lisinopril for 21 days showed increased levels of ACE2 in the lungs. Infection with SARS-CoV-2 led to massive decrease in lung ACE2 levels at 3 days post-infection (dpi) in treated and untreated animals, but Lisinopril-treated mice showed a fast recovery (5dpi) of ACE2 levels. Higher ACE2 levels in Lisinopril-treated mice led to remarkably higher lung viral loads at 3 and 6/7dpi. Lisinopril-treated mice showed decreased levels of the pro-inflammatory cytokines IL-6 and TNF-α in the serum and lungs at 6/7dpi. Marginal improvements in body weight, clinical score and survival were observed in Lisinopril-treated mice. No differences between treated and untreated infected mice were observed in respiratory function and lung histology. Lisinopril treatment showed both deleterious (higher viral loads) and beneficial (anti-inflammatory and probably anti-constrictory and anti-coagulant) effects in experimental COVID-19. These effects seem to compensate each other, resulting in marginal beneficial effects in terms of outcome for Lisinopril-treated animals.

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

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

Effects of ACE inhibitor/ARB therapy and long COVID on kidney disease: a retrospective cohort study using real-world data.

Background: The association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and severe acute respiratory syndrome coronavirus 2 susceptibility, particularly via ACE-2 receptor upregulation in the kidneys, raises concerns about potential kidney disease risks in long coronavirus disease (COVID) patients. This study explores the association of ACEI/ARB therapy on acute kidney injury (AKI), chronic kidney disease (CKD) and all-cause mortality in patients with and without long COVID. Methods: A retrospective cohort study using TriNetX datasets was conducted, with diagnoses of long COVID via International Classification of Diseases, Tenth Revision (ICD-10) codes and prescription for ACEI/ARB as the classification of four cohorts: long COVID ACEI/ARB users (LCAUs), long COVID ACEI/ARB non-users (LCANs), non-long COVID ACEI/ARB users (NLCAUs) and non-long COVID ACEI/ARB non-users (NLCANs). Multivariable stratified Cox proportional hazards regression models assessed the adjusted hazard ratios (aHRs) across groups. Additional analyses were conducted, including time-dependent exposure analysis and comparison with an active comparator, calcium channel blockers. Results: Our study included 18 168 long COVID and 181 680 propensity score-matched non-long COVID patients from October 2021 to October 2023. ACEI/ARB use did not significantly affect the risk of AKI or CKD when comparing LCAUs with LCANs and NLCAUs with NLCANs. However, a protective effect against all-cause mortality was observed {aHR 0.79 [95% confidence interval (CI) 0.65-0.93]} in the NLCAU group compared with the NLCAN group. Conversely, long COVID was associated with increased risks of CKD [aHR 1.49 (95% CI 1.03-2.14)] and all-cause mortality [aHR 1.49 (95% CI 1.00-2.23)] when comparing LCANs with NLCANs. The additional analyses support the primary findings. Conclusions: ACEI/ARB treatment does not increase the incidence of CKD or AKI, regardless of long COVID status. However, long COVID itself is associated with increasing risks of kidney diseases and all-cause mortality.

Comparison of the Efficacy and Safety of Sacubitril/Valsartan and Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Patients With Reduced Ejection Fraction Combined With Moderate-to-Severe Chronic Kidney Disease.

Background and Objectives: The efficacy and safety of a lower target dose of sacubitril/valsartan (angiotensin receptor neprilysin inhibitor [ARNI]) for treating heart failure with reduced ejection fraction (HFrEF) in Chinese patients with moderate-to-severe chronic kidney disease (CKD) remain unknown. We performed a retrospective study to compare the efficacy of ARNI with that of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) in patients with HFrEF and moderate-to-severe CKD. Methods: This retrospective study included 129 patients. An inverse probability of treatment weighting (IPTW) analysis was performed to compare the baseline characteristics and outcomes between the 2 groups. The incidence of death due to cardiovascular disease, rehospitalization due to heart failure after treatment, and improvement in cardiac function symptoms (New York Heart Association [NYHA]) were assessed after 12 months. Improvements of ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) level, left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD) were compared. Results: Compared with the ACEI/ARB group, the ARNI group, with 90.77% (59/65) in the lower target dose group, showed a lower rate of death due to cardiovascular disease (6.6% vs 0.9% after IPTW) and a lower incidence of rehospitalization (46.5% vs 30.4% after IPTW). NYHA class, estimated glomerular filtration rate, EF, NT-ProBNP levels, LVEDD, and LVESD improved in the ARNI group. None of the patients withdrew from treatment because of adverse drug reactions. Conclusion: Our study showed that ARNI resulted in a greater improvement in heart failure than ACEIs/ARBs in patients with HFrEF and moderate-to-severe CKD.

Beyond ß-Blockade: ACE Inhibitors Reduce Non-Cardiac Mortality in High Killip Grade AMI Patients.

OBJECTIVE: This study evaluates the 3-year clinical outcomes of high Killip grade (III/IV) acute myocardial infarction (AMI) patients treated with either ß-blockers (BB) and angiotensin-converting enzyme inhibitors (ACEI) or BB and angiotensin receptor blockers (ARB). METHODS: A total of 13,105 patients were registered at the Korea Acute Myocardial Infarction Registry at the National Institute of Health (KAMIR-NIH). Among them, 871 patients with high Killip classification AMI were divided into the BB + ACEI group (n = 489) and the BB + ARB group (n = 381). Following propensity score matching, 343 patients were selected in each group. All patients completed a 3-year follow-up period. RESULTS: The results indicate no significant differences between the BB + ACEI group and BB + ARB group in terms of cardiac death, recurrent myocardial infarction, and the rate of repeat percutaneous coronary intervention. However, the BB + ACEI group exhibited significantly lower risks in major adverse cardiac events (HR = 0.574, 95% CI: 0.421-0.783, p < .001), all-cause mortality (HR = 0.561, 95% CI: 0.404-0.778, p = .001), and non-cardiac death (HR = 0.365, 95% CI: 0.208-0.639, p < .001) compared to the BB + ARB group. CONCLUSION: Our results suggest that BB + ACEI treatment is more beneficial than BB + ARB for high Killip grade AMI patients. Additionally, the BB + ACEI group has a superior preventative effect on mortality compared to the BB + ARB group.

Are Sodium-Glucose Cotransporter-2 Inhibitors the Cherry on Top of Cardio-Oncology Care?

The increasing aging of the population combined with improvements in cancer detection and care has significantly improved the survival and quality of life of cancer patients. These benefits are hampered by the increase of cardiovascular diseases being heart failure the most frequent manifestation of cardiotoxicity and becoming the major cause of morbidity and mortality among cancer survivor. Current strategies to prevent cardiotoxicity involves different approaches such as optimal management of CV risk factors, use of statins and/or neurohormonal medications, and, in some cases, even the use of chelating agents. As a class, SGLT2-i have revolutionized the therapeutic horizon of HF patients independently of their ejection fraction or glycemic status. There is an abundance of data from translational and observational clinical studies supporting a potential beneficial role of SGLT2-i in mitigating the cardiotoxic effects of cancer patients receiving anthracyclines. These findings underscore the need for more robust clinical trials to investigate the effect on cardiovascular outcomes of the prophylactic SGLT2-i treatment in patients undergoing cancer treatment.

The Evolving Role of Calcium Channel Blockers in Hypertension Management: Pharmacological and Clinical Considerations.

Worldwide, hypertension is the leading risk factor for cardiovascular disease and death. An estimated 122 million people, per the American Heart Association in 2023, have been diagnosed with this common condition. It is generally agreed that the primary goal in the treatment of hypertension is to reduce overall blood pressure to below 140/90 mmHg, with a more optimal goal of 130/80 mmHg. Common medications for treating hypertension include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics. CCBs are one of the most widely studied agents and are generally recommended as first-line therapy alone and in combination therapies. This is largely based on the vast knowledge of CCB mechanisms and their minimal side effect profile. CCBs can be separated into two classes: dihydropyridine and non-dihydropyridine. Non-dihydropyridine CCBs act on voltage-dependent L-type calcium channels of cardiac and smooth muscle to decrease muscle contractility. Dihydropyridine CCBs act by vasodilating the peripheral vasculature. For many patients with only mild increases in systolic and diastolic blood pressure (e.g., stage 1 hypertension), the medical literature indicates that CCB monotherapy can be sufficient to control hypertension. In this regard, CCB monotherapy in those with stage 1 hypertension reduced renal and cardiovascular complications compared to other drug classes. Combination therapy with CCBs and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors has been shown to be an effective dual therapy based on recent meta-analyses. This article is a review of calcium channel blockers and their use in treating hypertension with some updated and recent information on studies that have re-examined their use. As for new information, we tried to include some information from recent studies on hypertensive treatment involving calcium channel blockers.

Meta-analysis of renin angiotensin aldosterone modulators mitigating Atrial Fibrillation risk in hypertensive patients.

INTRODUCTION: Hypertension is associated with left ventricular hypertrophy/enlargement/fibrosis and atrial ectopic rhythm, leading to an increased risk of Atrial Fibrillation (AF). We aimed to stratify the effect of Angiotensin Converting Enzyme Inhibitors (ACEi) and Angiotensin Receptor Blockers (ARB) on the risk of AF. METHODS: PubMed, Scopus, and Google Scholar databases were screened, and cross-citation was conducted for studies reporting AF in hypertensive patients on ACEi and ARB. Of 145 studies found till May 2023, 19 were included in this study. Binary random-effects models estimated the pooled odds ratios, I2 statistics assessed heterogeneity and sensitivity analysis was assessed using the leave-one-out method. RESULTS: 153,559 hypertensive patients met the inclusion criteria. For incidental AF, ACEi and ARB showed a significant decrease in both unadjusted (OR 0.75, 95% CI [0.66-0.85], I² = 20.79%, p=0.29) and adjusted risks (OR 0.76, 95% CI [0.62-0.93], I² = 88.41%, p<0.01). In recurrent AF, the unadjusted analysis showed no significant effect (OR 0.89, 95% CI [0.55-1.42], I² = 78.44%, p<0.01), while the adjusted analysis indicated a reduced risk (OR 0.62, 95% CI [0.50-0.76], I² = 65.71%, p<0.01). Leave-one-out sensitivity analysis confirmed these results. CONCLUSIONS: ACEi and ARB considerably decrease the risk of incidental and recurrent AF in hypertensive patients, emphasizing the importance of treating clinical hypertension with these drugs.

[Renoprotective treatments : renin-angiotensin-aldosterone system blockade and beyond]. / Néphroprotection médicamenteuse : au-delà du blocage du système rénine-angiotensine.

RENOPROTECTIVE TREATMENTS: RENIN-ANGIOTENSINALDOSTERONE SYSTEM BLOCKADE AND BEYOND. Patients with chronic kidney disease (CKD) require both etiological and symptomatic treatments to slow renal function decline. Reductions of protein and salt intakes are required. Pharmacological treatments combines blockade of the renin-angiotensin system, sodium-glucose co-transporter type 2 inhibitors and mineralocorticoid receptor antagonists in most diabetic patients. The albumin creatinine ration (ACR) in morning spot urine samples is now a therapeutic target both in diabetic and non-diabetic CKD patients.

NÉPHROPROTECTION MÉDICAMENTEUSE : AU-DELÀ DU BLOCAGE DU SYSTÈME RÉNINE-ANGIOTENSINE. Au-delà du traitement étiologique éventuel d'une maladie rénale chronique (MRC), et du contrôle de l'ensemble des facteurs de risque vasculaire, un traitement symptomatique est nécessaire pour ralentir le déclin de la fonction rénale. La prise en charge diététique permet de limiter les apports en protéines et en sel. Le traitement pharmacologique comporte nécessairement une association d'un bloqueur du système rénine-angiotensine-aldostérone, le plus souvent un inhibiteur du co-transport sodiumglucose de type 2 (SGLT2i) et chez certains diabétiques un antagoniste des récepteurs des minéralocorticoïdes (ARM). Le rapport albuminurie/créatininurie (RAC) sur un échantillon d'urine devient une cible thérapeutique aussi bien chez les non-diabétiques que chez les diabétiques.

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

BACKGROUND: 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. METHODS AND RESULTS: 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]). CONCLUSIONS: 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.

Predictors of overall mortality after endovascular abdominal aortic repair - A single centre study.

OBJECTIVES: A current and ongoing challenge is to reduce patient mortality after endovascular abdominal aortic repair (EVAR). This study aimed to assess the predictors of all-cause mortality after EVAR. METHODS: Data regarding the demographic characteristics, comorbidities, laboratory values, selected anatomical factors, post-EVAR treatment, surveillance and complications of patients who underwent elective EVAR for non-ruptured abdominal aortic aneurysm (AAA) between January 2010 and January 2021 were evaluated. Mortality was assessed until 10 October 2023. Multivariate analyses were performed after adjusting for age, hypertension, diabetes mellitus, dyslipidaemia, sex, smoking, number of lumbar arteries, patency of inferior mesenteric artery (IMA), IMA diameter and reinterventions. RESULTS: This study included 196 patients (183 men and 13 women) with a mean age of 72.4 ± 7.67 years. The overall mortality rate during a mean follow-up period of 5.75 ± 3.1 years was 50.0% (N = 98). The 2-, 5- and 10-year mortality rates were 9.7%, 32.0% and 66.6%, respectively. The mortality rates decreased by 59% in patients with reinterventions (hazard ratio [HR]: 0.41; 95% confidence interval [CI]: 0.23-0.73; p = .002) and by 59% in patients treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (HR: 0.41; 95% CI: 0.26-0.66; p < .001). Chronic anticoagulation was associated with 2.09-fold higher mortality (HR: 2.09; 95% CI: 1.19-3.67; p = .010), and coronary artery disease (CAD) was associated with 1.74-fold higher mortality (HR: 1.74; 95% CI: 1.09-2.78; p = .021). Pre-EVAR AAA diameter and 1-year post-EVAR sac diameter were positively associated with mortality (HR: 1.05; 95% CI: 1.03-1.08; p < .001, and HR: 1.05; 95% CI: 1.03-1.07; p < .001, respectively), that is, an increase of pre-EVAR and/or 1-year post-EVAR AAA diameter by 1 mm was associated with a 5% higher risk of all-cause mortality. CONCLUSIONS: Reinterventions and treatment with ACE inhibitors or ARBs may be associated with decreased post-EVAR mortality. A greater pre-EVAR, a post-EVAR AAA diameter, CAD and chronic anticoagulation were associated with higher all-cause mortality post-EVAR.

Effects of renin-angiotensin system inhibitor and beta-blocker use on mortality in older patients with heart failure with reduced ejection fraction in Japan.

Introduction: Guideline-directed medical therapy with renin-angiotensin system (RAS) inhibitors and beta-blockers has improved the survival of patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, it is unclear whether RAS inhibitors and beta-blockers can be administered to older patients with HF. Therefore, this study aimed to investigate the effects of beta-blockers and RAS inhibitors on the prognosis of older patients with HFrEF. Methods: Demographic, clinical, and pharmacological data from 1,061 patients with acute decompensated HF, enrolled in the Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI study), were analyzed to assess their impact on mortality. Additionally, a machine learning approach was applied to complement the conventional statistical model for analysis. Patients with HFrEF (n = 314) were divided into the all-cause mortality within 2 years group (n = 80) and the survivor group (n = 234). Results: Overall, 41.1% (129/314) of the patients were aged ≥80, and 25.5% (80/314) experienced all-cause mortality within 2 years. Furthermore, 57.6% (181/314) and 79.0% (248/314) were prescribed RAS inhibitors and beta-blockers, respectively. Our analysis showed that RAS inhibitor use was associated with reduced all-cause mortality and cardiac death in patients with HFrEF of all ages (P < 0.001), and beta-blocker use had an interaction with age. Machine learning revealed that the use of beta-blockers altered the risk of mortality, with a threshold of approximately 80 years of age. Beta-blocker use was associated with lower all-cause mortality and cardiac death in patients with HFrEF aged <80 years (P < 0.001) but not in those aged ≥80 years (P = 0.319 and P = 0.246, respectively). These results suggest that beta blockers may differ in their all-cause mortality benefits according to age. Conclusions: RAS inhibitors prevented all-cause mortality and cardiac death at all ages, whereas beta-blockers had different effects depending on the patient's age. This study suggested that the choice of beta-blockers and RAS inhibitors is more important in older patients with HFrEF than in younger patients with the same condition.