Sacubitril/valsartan has an underestimated impact on the right ventricle in patients with sleep-disordered breathing, especially central sleep apnoea syndrome.

BACKGROUND: Sacubitril/valsartan has been demonstrated to significantly improve left ventricular performance and remodelling in patients with heart failure. However, its effects on the right ventricle in patients with chronic heart failure and sleep-disordered breathing (SDB) have not been studied. AIM: To investigate the impact of sacubitril/valsartan treatment on right ventricular function in patients with SDB. METHODS: This was a subanalysis of an observational prospective multicentre study involving 101 patients. At inclusion, patients were evaluated by echocardiography and nocturnal ventilatory polygraphy, which allowed patients to be divided into three groups: "central-SDB"; "obstructive-SDB"; and "no-SDB". RESULTS: After 3 months of sacubitril/valsartan therapy, a positive impact on right ventricular function was observed. In the general population, tricuspid annular plane systolic excursion increased by +1.32±4.74mm (P=0.024) and systolic pulmonary artery pressure decreased by -3.1±10.91mmHg (P=0.048). The central-SDB group experienced the greatest echocardiographic improvement, with a significant increase in tricuspid annular plane systolic excursion of +2.1±4.9mm (P=0.045) and a significant reduction in systolic pulmonary artery pressure of -8.4±9.7mmHg (P=0.001). CONCLUSIONS: Sacubitril/valsartan improved right ventricular function in patients with heart failure and SDB after only 3 months of treatment. The greatest improvement in right ventricular function was observed in the central-SDB group.

The efficacy and safety of sacubitril/valsartan in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Sacubitril/valsartan, a new pharmacological class of angiotensin receptor neprilysin inhibitor, is beneficial to heart failure through blocking the degradation of natriuretic peptides and inhibiting renin-angiotensin-aldosterone system (RAAS) activation which also relate to the pathophysiologic mechanisms of chronic kidney disease (CKD). However, its effects on CKD remain unclear. To assess the efficacy and safety of sacubitril/valsartan for patients with CKD, we performed this meta-analysis. METHODS: The Embase, PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) that compared sacubitril/valsartan with ACEI/ARBs in patients with CKD whose estimated glomerular filtration rate (eGFR) was below 60 mL/min/1.73 m2. We adopted the Cochrane Collaboration tool for assessing the risk of bias. The effect size was estimated using the odds ratio (OR) with 95% confidence interval (CI). RESULTS: Six trials with a total of 6217 patients with CKD were included. In terms of cardiovascular events, sacubitril/valsartan attenuated the risk of cardiovascular death or heart failure hospitalization (OR: 0.68, 95% CI 0.61-0.76, P < 0.00001, I2 = 43%). With respect to renal function, sacubitril/valsartan prevented the incidence of serum creatinine (Scr) elevation among patients with CKD (OR: 0.79, 95% CI 0.67-0.95, P = 0.01, I2 = 0%). Subgroup analysis about eGFR demonstrated that with long follow-up, sacubitril/valsartan significantly decreased the number of patients with more than 50% reduction in eGFR compared with ACEI/ARBs (OR: 0.52, 95% CI 0.32-0.84, P = 0.008, I2 = 9%). In patients with CKD, the incidence of end-stage renal disease (ESRD) was reduced with sacubitril/valsartan treatment, despite no statistically significant difference between the two groups (OR: 0.59, 95% CI 0.29-1.20, P = 0.14, I2 = 0%). As for the safety, we found that sacubitril/valsartan was associated with the occurrence of hypotension (OR: 1.71, 95% CI 1.15-2.56, P = 0.008, I2 = 51%). However, there was no trend towards increasing the risk of hyperkalemia in patients who received sacubitril/valsartan (OR: 1.09, 95% CI 0.75-1.60, P = 0.64, I2 = 64%). CONCLUSION: This meta-analysis indicated that sacubitril/valsartan improved renal function and conferred effective cardiovascular benefits in patients with CKD, without serious safety issues being observed. Thus, sacubitril/valsartan may be a promising option for patients with CKD. Certainly, further large-scale randomized controlled trials are needed to confirm these conclusions. SYSTEMATIC REVIEW REGISTRATION: [ https://inplasy.com/inplasy-2022-4-0045/ ], identifier [INPLASY202240045].

Safety and feasibility of angiotensin receptor neprilysin inhibitor in real-world patients with acute decompensated heart failure.

BACKGROUND: The aim of this study was to determine the safety and feasibility of in-hospital sacubitril/valsartan initiation after clinical stabilization in patients with acute decompensated heart failure (ADHF) and reduced ejection fraction (EF). METHODS: This retrospective, multicenter observational study included patients admitted for ADHF in 2 Italian centers between February 2017 and January 2022. Feasibility was evaluated by assessing the proportion of patients discharged on sacubitril/valsartan. Key safety endpoints were the incidences of adverse events during hospitalization and during follow-up planned at 1 month, 3-6 months and 12-18 months after discharge. RESULTS: One hundred and twenty-two patients were included. Median age was 71 (60-78) years, 78% male, 63% New York Heart Association (NYHA) Class III at admission with a median left ventricular ejection fraction (EF) of 25% (20-30). During hospitalization, 94 (77%) patients were treated with intravenous diuretics, 39 (32%) with inotrope/vasopressor, 51 (42%) with continuous positive airway pressure ventilation and 7 (6%) were assisted with an intra-aortic balloon pump. Median time from hospitalization to sacubitril/valsartan initiation was 4 (2-7) days. Sacubitril/valsartan was started at a dosage of 12/13 mg in 52 (43%) patients, 24/26 mg in 61 (50%) patients and 49/51 mg in 8 (7%) patients. Overall, 111 (91%) patients were discharged on sacubitril/valsartan. At 12-18-month follow-up, the vast majority of patients were still on sacubitril/valsartan therapy. CONCLUSIONS: In-hospital initiation of sacubitril/valsartan treatment in real-world ADHF patients may be a safe and feasible treatment option.

A Retrospective Cohort Evaluation of a Pharmacist-Led Approach for Transitioning Patients to an Angiotensin Receptor-Neprilysin Inhibitor.

Background: Heart failure guidelines recommend replacing an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) with an angiotensin receptor neprilysin inhibitor (ARNI) to reduce morbidity and mortality in NYHA Class II-III patients with reduced ejection fraction (HFrEF). Objective: This study aims to determine if a pharmacist-led outpatient ARNI replacement and titration program led to more patients achieving target doses of ARNI compared to usual care. Methods: A single health system, retrospective electronic medical record review identified 791 patients with active ARNI prescriptions and at least two outpatient cardiology visits with a pharmacist or usual care provider between January 2015 through September 2018. The primary outcome was the percentage of patients who achieved a target ARNI dose of 97/103 mg twice daily. The secondary outcomes were the median dose achieved, number of visits required to achieve target dose, hospitalizations, and all-cause death. Results: ARNI was initiated and continued by a pharmacist in 64 patients and 727 by usual care. More patients in the pharmacist group, 60.9% (n = 39), achieved target dose vs. 18.0% (n = 131) of patients managed by usual care (95% CI, 0.31-0.55, p < 0.0001). The pharmacist group also had higher median total daily dose of ARNI (200 mg (IQR = 300) vs 100 mg (IQR = 100), p < 0.0001) and more likely to achieve a higher total daily dose in fewer visits. Conclusions: An advanced practice provider pharmacist-led outpatient ARNI replacement and titration program was more effective in achieving target doses of ARNI in HFrEF patients as compared to usual care.

Risk of Acute Kidney Injury Among Older Adults With Heart Failure and With Reduced Ejection Fraction Treated With Angiotensin-Neprilysin Inhibitor vs Renin-Angiotensin System Inhibitor in Routine Clinical Care.

BACKGROUND: The acute hemodynamic effects of sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), may result in early changes in kidney function, raising concerns about acute kidney injury (AKI), particularly in those who are naïve to renin-angiotensin system inhibitors (RASis). METHODS: We conducted a cohort study using U.S. Medicare fee-for-service claims data (2014-2017). Patients with HFrEF ≥ 65 years newly initiating ARNI or RASi, with no prior use of either drug class, were included. The primary outcome was hospitalization due to AKI as the primary discharge diagnosis, and the secondary outcome included AKI as a primary or secondary discharge diagnosis. AKI risks were described under an as-treated follow-up approach, with censoring on treatment discontinuation, switch, insurance disenrollment, death, or administrative censoring as well as an intent-to-treat approach. Propensity-score-based fine-stratification weighting was used to account for potential confounding by 81 pre-exposure characteristics. Cumulative incidence functions were used to report absolute risks, and Cox proportional hazards models were used to provide hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We included 27,166 patients with a mean (SD) age of 73 (7.3) years, and 4155 (15.3%) were initiating ARNI. After propensity score weighting, the 180-day cumulative incidence was 2.7% (2.4%-3.1%) among RASi initiators and 2.7% (2.2%-3.5%) among ARNI initiators for the primary outcome, and it was 6.5% (6.0%-7.1%) and 6.1% (5.2%-7.1%), respectively, for the secondary outcome under as-treated follow-up. HR (95% CI) comparing ARNI with RASi were 0.91 (95% CI: 0.72-1.16) for the primary outcome and 0.92 (95% CI: 0.79-1.08) for the secondary outcome. Similar results were observed in the intent-to-treat analysis. CONCLUSIONS: Among a large cohort of U.S. Medicare beneficiaries with HFrEF, ARNI treatment was not associated with higher rates of AKI than RASi treatment. These results provide reassurance for providers considering ARNI initiation in older patients who are RASi-naïve.

Sacubitril/Valsartan in Patients With Heart Failure and Concomitant End-Stage Kidney Disease.

Background Heart failure with reduced ejection fraction (HFrEF) is a chronic disease with substantial mortality. Management of HFrEF has seen significant breakthrough after the launch of neprilysin inhibitor. The PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impacton Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril/valsartan significantly reduces HFrEF mortality and the heart failure hospitalization rate. However, in patients with advanced kidney disease, who have the highest prevalence of heart failure, the efficacy and safety of sacubitril/valsartan remains uncertain. We aim to study the efficiency of sacubitril/valsartan in patients with end-stage kidney disease. Methods and Results Heart function was screened by echocardiogram among all patients with end-stage kidney disease in 2 hospitals. Patients with HFrEF received either sacubitril/valsartan or conventional treatment. Fifteen echocardiographic parameters were compared before and after treatment. After 1-year sacubitril/valsartan treatment, parameters of systolic (left ventricular ejection fraction 31.3% to 45.1%, P<0.0001; left ventricular end-systolic volume 95.7 to 70.1 mL, P=0.006; left ventricular internal diameter at end-systole phase 47.2 to 40.1 mm, P=0.005), and diastolic (E/A ratio 1.3 to 0.8, P=0.009; E/Med e' ratio 25.3 to 18.8, P=0.010) function improved in patients with HFrEF and end-stage kidney disease. These parameters were unchanged in the conventional treatment group. Serum potassium did not increase in the sacubitril/valsartan group. Conclusions Sacubitril/valsartan improves left ventricular systolic and diastolic function in patients with HFrEF and end-stage kidney disease.

Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy.

BACKGROUND: Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI. METHODS: In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes. RESULTS: Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF (P=0.79) or LAV (P =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume (P=0.025) and greater decline in LV mass index (P=0.037), increase in tissue Doppler e'lat (P=0.005), decrease in E/e'lat (P=0.045), and decrease in tricuspid regurgitation peak velocity (P=0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure. CONCLUSIONS: Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924727.

Trend of perceived quality of life and functional capacity in outpatients with chronic heart failure and in treatment with sacubitril/valsartan: a real-life experience.

BACKGROUND: Despite the use of optimal medical therapy, heart failure and reduced left ventricular ejection fraction (HFrEF) remains a leading cause of morbidity, mortality and health care costs. The introduction of angiotensin receptor/neprilysin inhibitors (ARNIs) had a revolutionary impact on the treatment of patients with HFrEF. The aim of the study was to monitor over time the perceived quality of life, the physical performance, the trend of BNP and NT-ProBNP and the NYHA functional class in patients with HFrEF during treatment with sacubitril/valsartan. METHODS: We enrolled 37 patients (63±10 years old, 76% men) who underwent a total of one-year follow-up. All patients underwent clinical evaluation, 6MWT, blood analysis (in particular, NT-pro-BNP and BNP, renal function test); Kansas City Cardiomyopathy Questionnaire (KCCQ) and the NYHA functional class assessment were also performed, at the beginning of the study and after 3, 6 and 12 months of therapy. RESULTS: We observed at each follow-up a significant improvement of KCCQ score, 6MWT, NT-ProBNP, BNP and NYHA class. However, analyzing the ∆% of variation of each single parameter, the improvement was not uniform in time. We also observed that only 37% of patients tolerated the full recommended dose of sacubitril/valsartan (97/103 mg b.i.d.); of the remaining, 40% tolerated the intermediate dose (49/51 mg b.i.d.) and 23% the minimum (24/26 md b.i.d.). CONCLUSIONS: Sacubitril/valsartan therapy improves significantly quality of life, physical effort resistance, BNP and NT-ProBNP and NYHA functional class in patients with HFrEF. Although not all the patients tolerated the maximum recommended dose, the beneficial effects were significant even at lower doses.

Diarrhoea with the angiotensin receptor neprilysin inhibitor sacubitril + valsartan: A pharmacovigilance study.

Diarrhoea is an adverse drug reaction of the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril + valsartan. It was also described with olmesartan and more recently with other angiotensin receptor blockers. The study was performed to compare diarrhoea reports in pharmacovigilance databases with sacubitril + valsartan and valsartan. The study used reports of diarrhoea with the ARNI sacubitril + valsartan registered: first in the French PharmacoVigilance Database (FPVD) and second in Vigibase®, the WHO Global Individual Case Safety Report database. After description of the main characteristics, disproportionality analyses were performed. Results are reported as reporting odds ratios (ROR) with 95% confidence interval. We found 29 reports of diarrhoea with sacubitril + valsartan in the FPVD and 686 in Vigibase®. With sacubitril + valsartan, diarrhoea occurred more frequently in males around 70 years with a median delay of 3 days. With valsartan, diarrhoea occurred more frequently in females around 68 years with a median delay of 0.5 days. In the FPVD, a significant association was found with sacubitril + valsartan in comparison with valsartan alone before (ROR = 8.78 [5.19-14.85]) and after (ROR = 11.19 [5.89-21.25]) exclusion of concomitant drugs known to be associated with diarrhoea. A significant association was also found in Vigibase® after adjustment on age, sex, reporter and its location (ROR = 1.31 [1.14-1.50]). Diarrhoea reported with sacubitril + valsartan has marked differences in gender, delay of occurrence and frequency of reporting in comparison with diarrhoea with valsartan. From a pharmacodynamic point of view, these results suggest a specific role of sacubitril in diarrhoea.

Clinical Effectiveness of Sacubitril/Valsartan Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction.

Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real-world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF ≤40% in the Get With The Guidelines-Heart Failure registry between October 2015 and December 2018, and eligible for sacubitril/valsartan. Associations between discharge prescription of sacubitril/valsartan and clinical outcomes were assessed after inverse probability of treatment weighting and adjustment for other HFrEF medications. Overall, 1551 (10.9%) patients were discharged on sacubitril/valsartan. Of those not prescribed sacubitril/valsartan, 7857 (62.0%) were prescribed an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. Over 12-month follow-up, compared with a discharge prescription of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, sacubitril/valsartan was independently associated with lower all-cause mortality (adjusted hazard ratio [HR], 0.82; 95% CI, 0.72-0.94; P=0.004) but not all-cause hospitalization (adjusted HR, 0.97; 95% CI, 0.89-1.07; P=0.55) or heart failure hospitalization (adjusted HR, 1.04; 95% CI, 0.91-1.18; P=0.59). Patients prescribed sacubitril/valsartan versus those without a prescription had lower risk of all-cause mortality (adjusted HR, 0.69; 95% CI, 0.60-0.79; P<0.001), all-cause hospitalization (adjusted HR, 0.90; 95% CI, 0.82-0.98; P=0.02), but not heart failure hospitalization (adjusted HR, 0.94; 95% CI, 0.82-1.08; P=0.40). Conclusions Among patients hospitalized for HFrEF, prescription of sacubitril/valsartan at discharge was independently associated with reduced postdischarge mortality compared with angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, and reduced mortality and all-cause hospitalization compared with no sacubitril/valsartan. These findings support the use of sacubitril/valsartan to improve postdischarge outcomes among older patients hospitalized for HFrEF in routine US clinical practice.

Use of Angiotensin Receptor Neprilysin Inhibitor in Patients on Maintenance Hemodialysis with Reduced Cardiac Ejection Fraction, Real-World Experience From a Single Center.

INTRODUCTION: Angiotensin receptor neprilysin inhibitor (ARNI) has been recommended by major guidelines as the leading therapy for heart failure with reduced ejection fraction (HFrEF). But little is known about its safety and effectiveness among maintenance hemodialysis patients with HFrEF in real-word practice. METHODS: An observational study was conducted among maintenance hemodialysis patients who received ARNI at our dialysis center. Enrollment commenced on June 1, 2018; and follow-up was completed on May 31, 2019. RESULTS: A total of 110 patients included in the study (age: 54.2 ± 14.8 y, 59% males). After 12 months of treatment, the average ARNI daily dose increased from 135 mg to 308 mg. The mean NT-pro- BNP concentration at baseline was 14455 pg/mL and 6435 pg/ mL after 12 months of treatment (P < .001). The left ventricular ejection fraction improved (35.1 vs. 49.8%, P < .001) over the 12 months, while left ventricular end-diastolic diameter, left ventricular mass index, left ventricular end-systolic diameter, and left atrial diameter also changed significantly (167.8 vs. 154.9 g/m, P < .001; 52.2 vs. 51.5 mm, P < .05; 35.9 vs. 36.9 mm, P < .001; 42.2 vs. 40.3 mm, P < .001). Furthermore, we found the quality of life and the NYHA symptom severity class improved significantly (P < .001). Kaplan-Meier analysis indicated that higher dose of ARNI and less vintage of HD were associated with best survival. CONCLUSION: In our study, ARNI appeared to be safe, relieved heart failure symptoms, and improved the scores of KCCQ physical and social activities in hemodialysis patients in real-world practice.

Real-world experience of angiotensin receptor/neprilysin inhibitor (ARNI) usage in Thailand: a single-center, retrospective analysis.

BACKGROUND: Treatment of heart failure with reduced ejection fraction (HFrEF) has been revolutionized by angiotensin receptor/neprilysin inhibitor (ARNI). ARNI has been shown to significantly reduce morbidity and mortality in a large, randomized controlled trial. However, real-world evaluation of ARNI with a diverse population is still limited. METHODS: HFrEF patients receiving angiotensin receptor/neprilysin inhibitor (ARNI) or standard HF treatment at a university hospital in Thailand were prospectively followed-up from January 2015 to December 2019. The primary outcome was a composite of all-cause mortality and heart failure hospitalization. Survival analysis and the Cox proportional hazard model were used to compare clinical outcomes between the two groups. RESULTS: During a follow-up period of 12 months, the primary outcome occurred in 10 patients in the ARNI group (11.5%) and 28 in the standard treatment group (28.0%) (hazard ratio 0.34; 95% CI: 0.15-0.80; p = 0.013). After adjustment for confounding factors, ARNI was significantly associated with a significant reduction in the primary outcome (HR 0.32, 95% CI: 0.13-0.82, p = 0.017). In addition, ARNI was also significantly associated with a decrease in the clinical signs and symptoms of HF, including dyspnea, orthopnea, and fatigue. Orthostatic hypotension was more frequently reported among the ARNI group than among the standard treatment group. The rates of target dose achievement were comparable between the two groups. CONCLUSION: In real-world practice, ARNI use was associated with a significant reduction in both clinical outcomes and symptom improvement, while orthostatic hypotension was more common in patients in the ARNI group than in patients in the standard treatment group.

Safety and Efficacy of the Combination of Sacubitril/Valsartan and SGLT2i in HFrEF Patients (SECSI Registry).

ABSTRACT: Recent studies have proven benefit of SGLT2i drugs in patients with heart failure with reduced ejection fraction (HFrEF), but their safety when combined with angiotensin-neprilysin inhibitor (ARNI) has not been established. The Safety and Efficacy of the Combination of Sacubitril/Valsartan and SGLT2i in HFrEF Patients registry was conducted to address this issue. SECSI registry is a consecutive, observational, retrospective, multicentre study conducted in 3 Heart Failure Units in Spain. It included 144 HFrEF patients who were treated with ARNI and iSGLT2. Data were collected at baseline, month 2, and month 6. The primary endpoint was the estimated glomerular filtration rate (eGFR), after the initiation of ARNI and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Secondary endpoints included potassium levels and functional class (New York Heart Association class). There were 3 prespecified subgroup analyses: Elderly patients (≥70 years), patients with chronic kidney disease (KDIGO classification G3), and the sequence of drug initiation. Mean age was 69.9 ± 10.1 years, and 110 (76.4%) were men. Left ventricular ejection fraction was 32 ± 7.8%, and most patients were symptomatic [123 (87.2%) New York Heart Association II/III/IV]. eGFR decreased at month 2 and this trend was maintained at month 6 [eGFR baseline 68.5 ± 17.3, month 2 62 ± 19.7 and month 6 64.7 ± 8.6 mL/min/1.73 m2 (P < 0.01 for both)]. In prespecified analysis, elder patients and those who simultaneously initiate both treatments showed the steeper decrease in eGFR. To conclude, co-administration of SGLT2i and ARNI in routine care in HFrEF patients produced a slight decrease in eGFR at 6 months of follow-up. This decrease was especially significant in elder patients and those who initiate both drugs simultaneously.