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1
Stanko, Peter, Kristina Repova, Tomas Baka, Kristina Krajcirovicova, Silvia Aziriova, Andrej Barta, Stefan Zorad, Michaela Adamcova, and Fedor Simko. "Sacubitril/Valsartan Alleviates Cardiac Remodeling and Dysfunction in L-NAME-Induced Hypertension and Hypertensive Heart Disease." Biomedicines 12, no. 4 (March 25, 2024): 733. http://dx.doi.org/10.3390/biomedicines12040733.
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There is ample evidence on the benefit of angiotensin receptor-neprilysin inhibitors (ARNIs) in heart failure, yet data regarding the potential protective action of ARNIs in hypertensive heart disease are sparse. The aim of this study was to show whether an ARNI exerts a protective effect in a model of Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension with a hypertensive heart and to compare this potential benefit with an angiotensin-converting enzyme inhibitor, captopril. Five groups of adult male Wistar rats were studied (14 per group) for four weeks: untreated controls; ARNI (68 mg/kg/day); L-NAME (40 mg/kg/day); L-NAME treated with ARNI; and L-NAME treated with captopril (100 mg/kg/day). L-NAME administration induced hypertension, accompanied by increased left ventricular (LV) weight and fibrotic rebuilding of the LV in terms of increased concentration and content of hydroxyproline in insoluble collagen and in total collagen and with a histological finding of fibrosis. These alterations were associated with a compromised systolic and diastolic LV function. Treatment with either an ARNI or captopril reduced systolic blood pressure (SBP), alleviated LV hypertrophy and fibrosis, and prevented the development of both systolic and diastolic LV dysfunction. Moreover, the serum levels of prolactin and prolactin receptor were reduced significantly by ARNI and slightly by captopril. In conclusion, in L-NAME-induced hypertension, the dual inhibition of neprilysin and AT1 receptors by ARNI reduced SBP and prevented the development of LV hypertrophy, fibrosis, and systolic and diastolic dysfunction. These data suggest that ARNI could provide protection against LV structural remodeling and functional disorders in hypertensive heart disease.
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Żelazny, Przemysław, Joanna Filipczak, Oliwer Sygacz, Sebastian Bróż, Sara Dankiewicz, Aleksandra Swora, Joanna Borowik, Wojciech Brodowski, Piotr Pawłowski, and Katarzyna Basta-Arciszewska. "Angiotensin Receptor Antagonist-Neprilysin Inhibitor (ARNI) therapy as a new hope in the population of people with heart failure with reduced ejection fraction (HFrEF)." Journal of Education, Health and Sport 12, no. 9 (September 8, 2022): 583–88. http://dx.doi.org/10.12775/jehs.2022.12.09.068.
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Introduction: Heart failure affects an estimated 23 million people, as many as 50% of whom suffer from a heart failure with reduced ejection fraction (HFrEF), in which the left ventricle ejection fraction is <40% and is accompanied by clinical symptoms. Given the high mortality rate in this group of patients and the continuous suboptimal control of the condition, novel pharmacotherapy regimens are needed to slow the progression of the disease. Preliminary studies report a positive effect of including an angiotensin receptor antagonist and neprilysin inhibitors (ARNIs) in this group of patients. Aim of the study: The aim of the study was to summarize the benefits of ARNI in a group of patients with HFrEF. Methods and materials: This article is based on the literature found in PubMed Database with use of keywords such as “ARNI”, “neprilysin inhibition”, HFrEF”, “heart failure” Results: The benefits of ARNI therapy in patients with HFrEF originate from reversing myocardial remodeling and increasing left ventricular ejection fraction. ARNI therapy is associated with reduced number of hospitalizations and a lower need for intensive treatment. In addition, ARNI use reduces the risk of cardiovascular death and is responsible for lower overall mortality rate compared to pharmacotherapy with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARBs). Conclusion: ARNIs in patients with HFrEF have a positive effect on the rate of cardiovascular hospitalization, as well as reducing cardiovascular-related mortality and total mortality. Future research studies should evaluate the predictive factors of response to treatment with this group of drugs using larger groups of patients.
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Gamero, Maira, Deisy Toloza-Moreno, Mariano Belaich, and Gloria Patricia Barrera Cubillos. "ARN de interferencia (ARNi): una herramienta eficaz en agrobiotecnología." Revista Colombiana de Biotecnología 24, no. 2 (December 1, 2022): 59–67. http://dx.doi.org/10.15446/rev.colomb.biote.v24n2.99397.
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El ARN de interferencia (ARNi) es un mecanismo evolutivamente conservado en la mayoría de las células eucariotas que permite silenciar genes mediante la degradación de ARN mensajero (ARNm) y la supresión de la síntesis de proteínas. En plantas, las moléculas de ARNi están involucradas en mecanismos de defensa contra patógenos y transposones, en la respuesta adaptativa al estrés, y en la expresión de genes relacionados con su crecimiento. El ARNi se considera una herramienta biotecnológica eficaz para silenciar la expresión de genes de microorganismos fitopatógenos, esto permite el diseño de bioplaguicidas ambientalmente seguros con una afinidad y selectividad, en muchos casos superior a la de los plaguicidas químicos. En esta revisión se señalan los últimos avances en la aplicación del ARNi en el contexto agrícola y su efectividad en el control biológico de fitopatógenos e insectos plaga. Asimismo, se presentan diversos ensayos experimentales cuyos resultados pueden ser la base para futuros bioproductos, además de algunos ejemplos disponibles en el mercado. Por último, se abordan aspectos de bioseguridad y consideraciones regulatorias necesarias para la aceptación y uso de esta tecnología a nivel global.
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Niemiec, Rafał, Irmina Morawska, Maria Stec, Wiktoria Kuczmik, Andrzej S. Swinarew, Arkadiusz Stanula, and Katarzyna Mizia-Stec. "ARNI in HFrEF—One-Centre Experience in the Era before the 2021 ESC HF Recommendations." International Journal of Environmental Research and Public Health 19, no. 4 (February 13, 2022): 2089. http://dx.doi.org/10.3390/ijerph19042089.
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Background: Sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor (ARNI), has demonstrated a survival benefit and reduces heart failure hospitalization in patients with heart failure with reduced left ventricular ejection fraction (HFrEF); however, our experience in this field is limited. This study aimed to summarize a real clinical practice of the use of ARNI in HFrEF patients hospitalized due to HFrEF in the era before the 2021 ESC HF recommendations, as well as assess their clinical outcome with regard to ARNI administration. Methods and Materials: Overall, 613 patients with HFrEF hospitalized in 2018–2020 were enrolled into a retrospective one-centre cross-sectional analysis. The study population was categorized into patients receiving (82/13.4%) and not-receiving (531/82.6%) ARNI. Clinical outcomes defined as rehospitalization, number of rehospitalizations, time to the first rehospitalization and death from any cause were analysed in the 1–2 year follow-up in the ARNI and non-ARNI groups, matched as to age and LVEF. Results: Clinical characteristics revealed the following differences between ARNI and non-ARNI groups: A higher percentage of cardiovascular implantable electronic devices (CIED) (p = 0.014) and defibrillators with cardiac resynchronization therapy (CRT-D) (p = 0.038), higher frequency of atrial fibrillation (p = 0.002) and history of stroke (p = 0.024) were in the ARNI group. The percentage of patients with HFrEF NYHA III/IV presented an increasing trend to be higher in the ARNI (64.1%) as compared to the non-ARNI group (51.5%, p = 0.154). Incidence of rehospitalization, number of rehospitalizations and time to the first rehospitalization were comparable between the groups. There were no differences between the numbers of deaths of any cause in the ARNI (28%) and non-ARNI (28%) groups. The independent negative predictor of death in the whole population of ARNI and non-ARNI groups was the coexistence of coronary artery disease (CAD) (beta= −0.924, HR 0.806, p = 0.011). Conclusions: Our current positive experience in ARNI therapy is limited to extremely severe patients with HFrEF. Regardless of the more advanced HF and HF comorbidities, the patients treated with ARNI presented similar mortality and rehospitalizations as the patients treated by standard therapy.
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Kim, Donghyun, Gyuho Jang, Jaetaek Hwang, Xiaofan Wei, Hyunsoo Kim, Jinbae Son, Sang-Jae Rhee, et al. "Combined Therapy of Low-Dose Angiotensin Receptor–Neprilysin Inhibitor and Sodium–Glucose Cotransporter-2 Inhibitor Prevents Doxorubicin-Induced Cardiac Dysfunction in Rodent Model with Minimal Adverse Effects." Pharmaceutics 14, no. 12 (November 28, 2022): 2629. http://dx.doi.org/10.3390/pharmaceutics14122629.
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Although cancer-therapy-related cardiac dysfunction (CTRCD) is a critical issue in clinical practice, there is a glaring lack of evidence regarding cardiotoxicity management. To determine an effective and suitable dosage of treatment using angiotensin receptor–neprilysin inhibitors (ARNI) with sodium–glucose cotransporter 2 inhibitors (SGLT2i), we adopted a clinically relevant rodent model with doxorubicin, which would mimic cardiac dysfunction in CTRCD patients. After the oral administration of drugs (vehicle, SGLT2i, ARNI, Low-ARNI/SGLT2i, ARNI/SGLT2i), several physiologic parameters, including hemodynamic change, cardiac function, and histopathology, were evaluated. Bulk RNA-sequencing was performed to obtain insights into the molecular basis of a mouse heart response to Low-ARNI/SGLT2i treatment. For the first time, we report that the addition of low-dose ARNI with SGLT2i resulted in greater benefits than ARNI, SGLT2i alone or ARNI/SGLT2i combination in survival rate, cardiac function, hemodynamic change, and kidney function against doxorubicin-induced cardiotoxicity through peroxisome proliferator-activated receptor signaling pathway. Low-dose ARNI with SGLT2i combination treatment would be practically beneficial for improving cardiac functions against doxorubicin-induced heart failure with minimal adverse effects. Our findings suggest the Low-ARNI/SGLT2i combination as a feasible novel strategy in managing CTRCD patients.
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Roksnoer, Lodi C. W., Richard van Veghel, Marian C. Clahsen van Groningen, René de Vries, Ingrid M. Garrelds, Usha M. Bhaggoe, Jeanette M. G. van Gool, et al. "Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor–neprilysin inhibition compared with AT1 receptor blockade alone." Clinical Science 130, no. 14 (June 1, 2016): 1209–20. http://dx.doi.org/10.1042/cs20160197.
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ARNI [dual AT1 (angiotensin II type 1) receptor–neprilysin inhibition] exerts beneficial effects on blood pressure and kidney function in heart failure, compared with ARB (AT1 receptor blockade) alone. We hypothesized that ARNI improves cardiac and kidney parameters in diabetic TGR(mREN2)27 rats, an angiotensin II-dependent hypertension model. Rats were made diabetic with streptozotocin for 5 or 12 weeks. In the final 3 weeks, rats were treated with vehicle, irbesartan (ARB) or irbesartan+thiorphan (ARNI). Blood pressure, measured by telemetry in the 5-week group, was lowered identically by ARB and ARNI. The heart weight/tibia length ratio in 12-week diabetic animals was lower after ARNI compared with after ARB. Proteinuria and albuminuria were observed from 8 weeks of diabetes onwards. ARNI reduced proteinuria more strongly than ARB, and a similar trend was seen for albuminuria. Kidneys of ARNI-treated animals showed less severe segmental glomerulosclerosis than those of ARB-treated animals. After 12 weeks, no differences between ARNI- and ARB-treated animals were found regarding diuresis, natriuresis, plasma endothelin-1, vascular reactivity (acetylcholine response) or kidney sodium transporters. Only ARNI-treated rats displayed endothelin type B receptor-mediated vasodilation. In conclusion, ARNI reduces proteinuria, glomerulosclerosis and heart weight in diabetic TGR(mREN2)27 rats more strongly than does ARB, and this occurs independently of blood pressure.
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Ohnewein, Bernhard, Zornitsa Shomanova, Vera Paar, Albert Topf, Peter Jirak, Lukas Fiedler, Christina Granitz, et al. "Effects of Angiotensin Receptor-Neprilysin Inhibitors (ARNIs) on the Glucose and Fat Metabolism Biomarkers Leptin and Fructosamine." Journal of Clinical Medicine 12, no. 9 (April 24, 2023): 3083. http://dx.doi.org/10.3390/jcm12093083.
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(1) Background: Heart failure with reduced ejection fraction (HFrEF) remains a major health burden. Angiotensin-Receptor-Neprilysin-Inhibitors (ARNIs) are an established HFrEF therapy which increases natriuretic peptide levels by inhibiting neprilysin. Leptin is a lipid metabolism parameter, which is also involved in glucose metabolism and is suggested to correlate with HF burden. While the hormone also seems to interact with neprilysin, potential associations with ARNI therapy have not been investigated yet. (2) Methods: To study this issue, we measured levels of leptin and fructosamine in consecutive 72 HFrEF patients before initiation of ARNI therapy and 3–6 months after initiation of therapy in two European centers. Biomarker levels were correlated with clinical parameters including ejection fraction, LVEF, and NYHA class. (3) Results: During a follow-up of up to 6 months, clinical parameters improved significantly (LVEF: 30.2 ± 7.8% to 37.6 ± 10.0%, (p < 0.001) and a significant improvement of the mean NYHA class with initial 32 patients in NYHA III or IV and 8 patients in NYHA class III/IV during the follow up (p < 0.001). The initial NT-proBNP levels of 2251.5 ± 2566.8 pg/mL significantly improved to 1416.7 ± 2145 pg/mL, p = 0.008) during follow up. ARNI therapy was also associated with an increase in leptin levels (17.5 ± 23.4 µg/L to 22.9 ± 29.3, p < 0.001) and furthermore, affected glucose metabolism indicated by elevation of fructosamine values (333.9 ± 156.8 µmol/L to 454.8 ± 197.8 µmol/L, p = 0.013). (4) Conclusion: while in the early phase of therapy, ARNI promotes clinical improvement of HFrEF, and it also seems to affect fat and glucose parameters, indicating significant metabolic implications of this therapy regime.
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Jadhav, Uday M., V. K. Chopra, S. Ray, and A. Oomman. "Initiation, Treatment Response Evaluation, and Safety Monitoring of Angiotensin Receptor/Neprilysin Inhibitors (Sacubitril/Valsartan) in the Management of Heart Failure in India: An Expert Group Recommendations." Journal of Indian College of Cardiology 13, no. 4 (2023): 141–46. http://dx.doi.org/10.4103/jicc.jicc_22_23.
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Angiotensin receptor/neprilysin inhibitors (ARNI) have become a pillar of heart failure (HF) management. Clinicians gain practical insight into the use of sacubitril/valsartan in patients with HF with reduced ejection fraction (EF) from a comprehensive overview based on clinical experience with ARNI therapy. The objective was to develop a consensus document addressing common concerns regarding the use of ARNI in patients with HF in clinical settings in India. Subject matter experts (SMEs) from India with decision-making expertise in the management of HF were identified to address experiences of ARNI use in Indian patients, its function in reversing myocardial remodeling, improvement in health status, and its safety. In regional meetings, five SMEs from India who consented to participate discussed data from practical experiences and current evidence. ARNI has been shown to substantially enhance EF 5%–10% in a majority of HF patients, although the range of improvement could vary widely in a few patients. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blocker antagonists have been eclipsed by ARNI. Patients who have diminished or declining estimated glomerular filtration rates are more likely than those with normal renal function to experience hyperkalemia. It is prudent to consistently monitor potassium levels in patients with borderline chronic kidney disease. In India, potassium binders may be used to temporarily control hyperkalemia caused by ARNI. Patients with a systolic blood pressure of <100 mmHg may initiate taking ARNI while being tracked for clinical symptoms. In clinical practice, symptomatic improvement with ARNI is observed soon after initiating, even before alterations noted in echocardiography.
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Ishizaka, Mio, Yurika Yamamori, Huai-Hsun Hsu, Yuichi Miyagawa, Naoyuki Takemura, and Mizuki Ogawa-Yasumura. "Study on the Effects of Angiotensin Receptor/Neprilysin Inhibitors on Renal Haemodynamics in Healthy Dogs." International Journal of Molecular Sciences 25, no. 11 (June 3, 2024): 6169. http://dx.doi.org/10.3390/ijms25116169.
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An angiotensin receptor/neprilysin inhibitor (ARNI), a heart failure treatment, is a combination drug made up of sacubitril, a neprilysin inhibitor, and valsartan, a vascular receptor blocker. No human or veterinary studies regarding the effect of ARNI on renal haemodynamics in the absence of cardiac or renal issues exist. Therefore, we investigated the effect of ARNI on renal haemodynamics in five healthy dogs. ARNI was administered to all five dogs at an oral dose of 20 mg/kg twice daily for 4 weeks. Renal haemodynamics were assessed on the day before ARNI administration (BL), on Day 7, and on Day 28. The glomerular filtration rate (GFR) significantly increased on Day 28 compared to BL and Day 7, whereas renal plasma flow increased on Day 7 and Day 28 compared to BL. Systolic blood pressure significantly decreased between BL and Day 28. Plasma atrial natriuretic peptide (ANP) concentrations increased on Day 7 compared to BL. Additionally, ANP concentrations increased on Day 28 in three of the five dogs. Different ANP concentrations were observed in the remaining two dogs. Both urine output volume and heart rate remained relatively stable and did not exhibit significant change. In conclusion, ARNI may enhance renal haemodynamics in healthy dogs. ARNI could be a valuable drug for treating both heart and kidney disease in dogs.
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Einecke, Dirk. "Neue Therapieoption ARNI." MMW - Fortschritte der Medizin 158, no. 12 (June 2016): 70. http://dx.doi.org/10.1007/s15006-016-8461-0.
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Red. "ARNI punktet erneut." MMW - Fortschritte der Medizin 159, no. 2 (February 2017): 74. http://dx.doi.org/10.1007/s15006-017-9234-0.
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DE. "ARNI übertrifft Sartan." CME 12, no. 9 (September 2015): 43. http://dx.doi.org/10.1007/s11298-015-1493-4.
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Chopra, H. K., G. S. Wande, Tiny Nair, C. K. Ponde, Navin C. Nanda, Jagat Narula, Saumitra Ray, et al. "Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India." Journal of the Association of Physicians of India 71, no. 04 (April 1, 2023): 73–82. http://dx.doi.org/10.5005/japi-11001-0230.
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Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), β-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).
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Poglajen, Gregor, Ajda Anžič-Drofenik, Gregor Zemljič, Sabina Frljak, Andraž Cerar, Renata Okrajšek, Miran Šebeštjen, and Bojan Vrtovec. "Long-Term Effects of Angiotensin Receptor–Neprilysin Inhibitors on Myocardial Function in Chronic Heart Failure Patients with Reduced Ejection Fraction." Diagnostics 10, no. 8 (July 28, 2020): 522. http://dx.doi.org/10.3390/diagnostics10080522.
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Background. We sought to evaluate the long-term effects of angiotensin receptor blocker–neprilysin inhibitor (ARNI) therapy on reverse remodeling of the failing myocardium in HFrEF patients. Methods. We performed a prospective non-randomized longitudinal study on 228 HFrEF patients treated with ARNI at our center. Prior to ARNI introduction all patients received stable doses of ACEI/ARB for at least six months. Clinical, biochemical and echocardiography data were obtained at ARNI introduction and 12-month follow-up. Results At follow-up, we found significant improvements in LVEF (29.7% ± 8% vs. 36.5% ± 9%; p < 0.001), LVOT-VTI (14.8 ± 4.2 cm vs. 17.2 ± 4.2 cm; p < 0.001), TAPSE (1.7 ± 0.5 cm vs. 2.1 ± 0.6 cm; p < 0.001) and LV-EDD (6.5 ± 0.8 cm vs. 6.3 ± 0.9 cm; p = 0.001). NT-proBNP serum levels also decreased significantly (1324 (605, 3281) pg/mL vs. 792 (329, 2022) pg/mL; p = 0.001). A total of 102 (45%) of patients responded favorably to ARNI (ΔLVEF < +5%; Group A) and 126 (55%) patients achieved ΔLVEF ≥ +5% (Group B). The two groups differed significantly in age, heart failure etiology, baseline LVEF and baseline NT-proBNP. On multivariable analysis, nonischemic heart failure, LVEF < 30% and NT-proBNP < 1500 pg/mL emerged as independent correlates of favorable response to ARNI therapy. Conclusion. ARNI therapy appears to improve echocardiographic parameters of left and right ventricular function in HFrEF patients above the effect of pre-existing optimal medical management. These effects may be particularly pronounced in patients with nonischemic heart failure, LVEF < 30% and lower degree of neurohumoral activation.
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Sobiborowicz-Sadowska, Aleksandra M., Katarzyna Kamińska, and Agnieszka Cudnoch-Jędrzejewska. "Neprilysin Inhibition in the Prevention of Anthracycline-Induced Cardiotoxicity." Cancers 15, no. 1 (January 3, 2023): 312. http://dx.doi.org/10.3390/cancers15010312.
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Anthracycline-induced cardiotoxicity (AIC) poses a clinical challenge in the management of cancer patients. AIC is characterized by myocardial systolic dysfunction and remodeling, caused by cardiomyocyte DNA damage, oxidative stress, mitochondrial dysfunction, or renin-angiotensin-aldosterone system (RAAS) dysregulation. In the past decade, after positive results of a PARADIGM-HF trial, a new class of drugs, namely angiotensin receptor/neprilysin inhibitors (ARNi), was incorporated into the management of patients with heart failure with reduced ejection fraction. As demonstrated in a variety of preclinical studies of cardiovascular diseases, the cardioprotective effects of ARNi administration are associated with decreased oxidative stress levels, the inhibition of myocardial inflammatory response, protection against mitochondrial damage and endothelial dysfunction, and improvement in the RAAS imbalance. However, data on ARNi’s effectiveness in the prevention of AIC remains limited. Several reports of ARNi administration in animal models of AIC have shown promising results, as ARNi prevented ventricular systolic dysfunction and electrocardiographic changes and ameliorated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and the inflammatory response associated with anthracyclines. There is currently an ongoing PRADAII trial aimed to assess the efficacy of ARNi in patients receiving breast cancer treatment, which is expected to be completed by late 2025.
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Lupi, Alessandro, Sara Ariotti, Doranna De Pace, Irene Ferrari, Stefano Bertuol, Lorenzo Monti, Luigina Guasti, Giovanni Vincenzo Gaudio, and Carlo Campana. "Sacubitril/Valsartan to Treat Heart Failure in a Patient with Relapsing Hairy Cell Leukaemia: Case Report." Clinical Medicine Insights: Cardiology 15 (January 2021): 117954682110107. http://dx.doi.org/10.1177/11795468211010706.
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Experience with angiotensin-receptor neprilysin inhibitors (ARNI) in oncologic patients with heart failure (HF) is limited. We report a case of ARNI started as first-choice therapy in a patient with relapsing hairy cell leukaemia (HCL) and HF with depressed left ventricular ejection fraction (LVEF). A middle-aged male, previously treated with rituximab for HCL, was scheduled for cardiologic screening before starting a new antineoplastic therapy for cancer relapse. The patient had symptomatic HF with reduced LVEF and high NT-proBNP levels. In this patient, early ARNI treatment was well tolerated and produced a rapid and durable improvement of symptoms, LVEF and NT-proBNP levels. Consequently, the oncologic team could start an experimental treatment with obinutuzumab, with complete HCL remission. In conclusion, in this patient with HCL and HF, ARNI therapy was safe and effective, contributing to undelayed cancer treatment.
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Várallyay, Zoltán, and Ede Kékes. "Az angiotenzinreceptor-blokkoló/neprilizininhibitor (ARNI) terápia eredményessége a szívelégtelenség kezelésében : 2021 ARNI, VIDI, VICI..." Hypertonia és Nephrologia 26, no. 2 (2022): 71–76. http://dx.doi.org/10.33668/hn.26.010.
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Az ARNI (valzartán/szakubitril) terápia egy új típusú hatástani csoport tagjaként számos klinikai evidenciával rendelkezik a szívelégtelenség szinte teljes spektrumában, különösen csökkent bal kamrai ejekciós frakció és társult hypertonia esetén. Bemutatjuk az ARNI-kezeléssel foglalkozó, legfontosabb és megfelelő evidenciával rendelkező alapvető tanulmányokat és a kezelés eredményességét szívelégtelenségben. A vizsgálatok kedvező eredményei alapján a szakmai irányelvekben egyre meghatározóbb ajánlásként jelenik meg az ARNI adásának az indikációja. Alkalmazása a mindennapi klinikai gyakorlatban hatékony, biztonságos terápiás segítséget jelent az ismerten rossz prognózisú szívelégtelenségben szenvedő betegek számára. A szer már hazánkban is elérhetővé vált.
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Abumayyaleh, Mohammad, Christina Pilsinger, Ibrahim El-Battrawy, Marvin Kummer, Jürgen Kuschyk, Martin Borggrefe, Andreas Mügge, Assem Aweimer, and Ibrahim Akin. "Clinical Outcomes in Patients with Ischemic versus Non-Ischemic Cardiomyopathy after Angiotensin-Neprilysin Inhibition Therapy." Journal of Clinical Medicine 10, no. 21 (October 27, 2021): 4989. http://dx.doi.org/10.3390/jcm10214989.
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Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.
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Genç, Ahmet, and Gülsüm Meral Yılmaz Öztekin. "Effect of sacubutril/valsartan on Tp-e, QT, QTc, Tp-e/QTc parameters in heart failure with reduced ejection fraction." Cukurova Medical Journal 49, no. 1 (March 29, 2024): 47–53. http://dx.doi.org/10.17826/cumj.1377925.
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Purpose: The purpose of this study is to evaluate ventricular repolarization before, at the first month, and sixth month after Sacubutril/Valsartan, an angiotensin receptor neprilysin inhibitor (ARNI) treatment in heart failure patients with reduced ejection fraction (HFrEF).
Materials and Methods: We included 49 patients with HFrEF who switched to ARNI therapy. The 12-lead electrocardiography (ECG) was evaluated before ARNI therapy and also during the first and sixth months of the therapy. We evaluated demographic, clinical, and laboratory parameters, as well as medications and ECG data, including heart rate. Additionally, we examined QT, QTc, Tp-e, Tp-e calculated (Tp-ec), Tp-ec/QTc, Tp-e/QT, and Tp-e/QTc.
Results: After receiving ARNI treatment, ventricular repolarization indices were significantly reduced in the first and sixth months compared to before treatment. Specifically, the QTc values decreased from 457.6 ms to 443.8 ms, and the Tp-e/QT ratio decreased from 0.21±0.03 to 0.19±0.03. Additionally, the QTc values decreased from 457.6 ms to 444.9 ms, and the Tp-e/QT ratio decreased from 0.21±0.03 to 0.18±0.03. However, when the first and sixth months under ARNI treatment were compared, no significant difference was found (QTc: 443.8 ms vs. 444.9 ms, Tp-e/QT: 0.19±0.03 vs. 0.18±0.003).
Conclusion: ARNI treatment in HFrEF positively affected QTc, Tp-e, and Tp-ec intervals and Tp-e/QT, Tp-e/QTc, and Tp-ec/QTc ratios, which are indicators of ventricular repolarization. Moreover, this effect started in the first month and continued in the sixth month.
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Fahriannor, Fahriannor. "Sufi Healing Menurut Akademisi (Praktik Batatamba, Amalan dan Spiritual)." Al Qalam: Jurnal Ilmiah Keagamaan dan Kemasyarakatan 16, no. 1 (January 7, 2022): 60. http://dx.doi.org/10.35931/aq.v16i1.772.
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Kajian ini mengungkap tentang Sufi Healing menurut akademisi, yaitu praktik batatamba Arni, Amalan dan pengalaman ruhaninya dengan menggunakan studi analisis dari sisi syari’at dan tradisi sufi. Fokus kajian ini adalah bagaimana pelaksanaan Sufi Healing dari sudut seorang akademisi serta mengungkap bagaimana pengalaman spiritualnya. Hasil yang diperoleh dari kajian ini adalah bahwa praktik batatamba Arni memiliki kesamaan dengan praktik Rasulullah dalam healingnya, yaitu menggunakan media air dan tiupan. Adapun pasien yang letaknya sangat jauh. Arni menggunakan media elektronik yaitu Handphone, dengan cara dihubungkan secara langsung kepada pasien. Sedangkan bacaan-bacaan Arni dalam batatamba berasal dari ayat-ayat Al-Qur’an yang diimbangi dengan amalan-amalan sunnah. Kemudian pengalaman ruhaninya memiliki kesamaan dengan yang dialami oleh para sufi terdahulu seperti bermimpi dengan Rasulullah, Malaikat dan ulama. Oleh sebab itulah, menjadi penting bagi seorang muslim untuk memahami aspek syari’at sebelum bergerak di bidang healing atau batatamba, sehingga media dan amalan yang digunakan tidak bertentangan dengan ajaran Islam.
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Nishikimi, Toshio, and Yasuaki Nakagawa. "B-Type Natriuretic Peptide (BNP) Revisited—Is BNP Still a Biomarker for Heart Failure in the Angiotensin Receptor/Neprilysin Inhibitor Era?" Biology 11, no. 7 (July 9, 2022): 1034. http://dx.doi.org/10.3390/biology11071034.
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Myocardial wall stress, cytokines, hormones, and ischemia all stimulate B-type (or brain) natriuretic peptide (BNP) gene expression. Within the myocardium, ProBNP-108, a BNP precursor, undergoes glycosylation, after which a portion is cleaved by furin into mature BNP-32 and N-terminal proBNP-76, depending on the glycosylation status. As a result, active BNP, less active proBNP, and inactive N-terminal proBNP all circulate in the blood. There are three major pathways for BNP clearance: (1) cellular internalization via natriuretic peptide receptor (NPR)-A and NPR-C; (2) degradation by proteases in the blood, including neprilysin, dipeptidyl-peptidase-IV, insulin degrading enzyme, etc.; and (3) excretion in the urine. Because neprilysin has lower substrate specificity for BNP than atrial natriuretic peptide (ANP), the increase in plasma BNP after angiotensin receptor neprilysin inhibitor (ARNI) administration is much smaller than the increase in plasma ANP. Currently available BNP immunoassays react with both mature BNP and proBNP. Therefore, BNP measured with an immunoassay is mature BNP + proBNP. ARNI administration increases mature BNP but not proBNP, as the latter is not degraded by neprilysin. Consequently, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase in mature BNP mediated by inhibiting degradation by neprilysin, which lowers plasma BNP levels. These results suggest that even in the ARNI era, BNP can be used for diagnosis and assessment of the pathophysiology and prognosis of heart failure, though the mild increases early during ARNI administration should be taken into consideration.
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Einecke, Dirk. "ARNI vorteilhaft nach Herzinfarkt?" MMW - Fortschritte der Medizin 163, no. 12 (June 2021): 21. http://dx.doi.org/10.1007/s15006-021-0118-y.
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Stiefelhagen, Peter. "ARNI — ein neues Wirkprinzip." MMW - Fortschritte der Medizin 157, no. 20 (November 2015): 65. http://dx.doi.org/10.1007/s15006-015-7554-5.
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Einecke, Dirk. "Wer profitiert von ARNI?" MMW - Fortschritte der Medizin 159, S3 (October 30, 2017): 88. http://dx.doi.org/10.1007/s15006-017-0228-8.
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Grübler, Beate. "ARNI von Anfang an." MMW - Fortschritte der Medizin 165, no. 17 (September 28, 2023): 62. http://dx.doi.org/10.1007/s15006-023-3013-x.
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Arcari, L., E. Belmonte, D. Manzo, G. Camastra, and L. Cacciotti. "INCIDENCE AND DETERMINANTS OF SUB–OPTIMAL DRUG TREATMENT IN CHRONIC HEART FAILURE: A SINGLE CENTER PILOT SURVEY." European Heart Journal Supplements 26, Supplement_2 (April 2024): ii85. http://dx.doi.org/10.1093/eurheartjsupp/suae036.205.
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Abstract Background The latest European Society of Cardiology guidelines on heart failure (HF) recommend a pharmacological treatment including 4 drugs (ARNI or ACE–inhibitor, beta–blocker, SGLT–2 inhibitor and MRA), with a class I indication in patients with HFrEF. However, the implementation of the 4 pillars approach is still largely insufficient in clinical practice. The aim of the present study was to investigate incidence and determinants of sub–optimal HF drug–treatment. Methods We conducted a 2–months survey in the heart failure outpatient clinic at our first–level community hospital. Physicians were asked to record the drug treatment patients were actually taking, and in the absence of one of the four pillars drug, to specify the underlying reason. Results 100 patients were enrolled, mean age 72±10 years old, 32 females. There were 36 HFpEF and 64 HFrEF patients. Quadruple therapy was present in 67 (HFpEF 58%, HFrEF 72%). Prescription rates of the four pillars drugs were: ARNI/ACE–inhibitor 96% (HFpEF 92%, HFrEF 98%; p=0.097), beta–blockers 98% (HFpEF 97%, HFrEF 98%; p>0.99), SGLT–2 inhibitor 81% (HFpEF 72%, HFrEF 86%; p=0.093), MRA 82% (HFpEF 78%, HFrEF 84%; p=0.410). No significant associations between age and sex with pharmacological treatments were noted (all p>0.05). Considering left ventricular ejection fraction (LVEF) as a continuous variable, patients under ARNI and SGLT–2 inhibitor treatments had lower values (43±10% vs 36±9%, p=0.001 and 43±9% vs 38±10%, p=0.034 respectively). Main reasons absent treatment were presence of chronic kidney disease with or without hyperkalemia (ARNI: 7%; ACE–inhibitor: 1%; BB: 0%; SGLT–2 inhibitor: 3%; MRA: 8%) and LVEF value (ARNI: 7%; Ace–inhibitor: 0%; BB: 0%; SGLT–2 inhibitor: 3%; MRA: 2%). Beta–blocker was not prescribed in 2% of the patients due to bradycardia. Hypotension leading to treatment discontinuation was more common in the ARNI group (ARNI: 8%; ACE–inhibitor: 1%; others: 0%). Conclusions In our sample, more than two thirds of HF patients were prescribed the quadruple heart failure pharmacological treatment. Save for hypotension in the ARNI treated patients, a high drug tolerability was observed. Physician–guided lack of prescription was influenced by the presence of chronic kidney disease and absent drug reimbursement due to LVEF cut–off as per AIFA criteria at the time of prescription. Results of this survey highlights potential areas to improve adherence to guidelines–directed medical treatments.
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Zubaid, Mohammad, Wafa Rashed, Mustafa Ridha, Nooshin Bazargani, Adel Hamad, Rashed Al Banna, Nidal Asaad, et al. "Implementation of Guideline-Recommended Therapies for Patients With Heart Failure and Reduced Ejection Fraction: A Regional Arab Middle East Experience." Angiology 71, no. 5 (February 18, 2020): 431–37. http://dx.doi.org/10.1177/0003319720905742.
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We describe the characteristics of ambulatory patients with heart failure with reduced ejection fraction (HFrEF) in the Gulf region (Middle East) and the implementation of guideline-recommended treatments. We included 2427 HFrEF outpatients (mean age 59 ± 13 years, 75% males and median left ventricular ejection fraction [LVEF] of 30%). A high proportion of patients received guideline-recommended medications (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin receptor blocker [ARB]/angiotensin receptor-neprilysin inhibitor [ARNI] 87%, β-blocker 91%, mineralocorticoid antagonist [MRA] 64%). However, only a minority of patients received guideline-recommended target doses (ACEI/ARB/ARNI 13%, β-blocker 27%, and MRA 4.4%). Old age was a significant independent predictor for not prescribing treatment ( P < .001 for ACEI/ARB/ARNI and MRA; and P = .002 for β-blockers). Other independent predictors were chronic kidney disease (for both ACEI/ARB/ARNI and MRA, P < .001) and higher LVEF ( P = .014 for β-blockers and P < .001 for MRA). Patients with HFrEF managed by heart failure specialists more often received recommended target doses of ACEI/ARB/ARNI (40% vs 11%, P < .001) and β-blockers (56% vs 26%, P < .001) compared to those treated by general cardiologists. Although the majority of our patients with HFrEF received guideline-recommended medications, the doses they were prescribed were suboptimal. Understanding the reasons behind this is important for improved practice.
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Chopra, H. K., G. S. Wander, C. K. Ponde, Navin C. Nanda, Dinesh Khullar, K. Venugopal, Saumitra Ray, et al. "The Power and Promise of Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure Management: National Consensus Statement." Journal of The Association of Physicians of India 71, no. 2 (February 1, 2023): 70–77. http://dx.doi.org/10.5005/japi-11001-0209.
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Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril–Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril–Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril–Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril–Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40–50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk
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Hsiao, Fu-Chih, Chia-Pin Lin, Chun-Chen Yu, Ying-Chang Tung, and Pao-Hsien Chu. "Angiotensin Receptor-Neprilysin Inhibitors in Patients With Heart Failure With Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Retrospective Multi-Institutional Study." Frontiers in Cardiovascular Medicine 9 (March 8, 2022). http://dx.doi.org/10.3389/fcvm.2022.794707.
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BackgroundData regarding using angiotensin receptor-neprilysin inhibitor (ARNI) in patients with both heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (CKD) are limited.Methods and ResultsBetween January 2016 and December 2018, patients with HFrEF and advanced CKD (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73 m2) were identified from a multi-institutional database in Taiwan. Patients who had never been prescribed with an ARNI, angiotensin-converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB) were excluded. We used inverse probability of treatment weighting (IPTW) to balance baseline covariates, and compared outcomes between ARNI and ACEI/ARB users. There were 206 patients in the ARNI group and 833 patients in the ACEI/ARB group. After IPTW adjustment, the mean ages (65.1 vs. 66.6 years), male patients (68.3 vs. 67.9%), left ventricular ejection fraction (30.5 vs.31.2%), eGFR (20.9 vs. 20.3 mL/min/1.73 m2) were comparable in the ARNI and ACEI/ARB groups. Over 85% of the patients had beta-blockers prescriptions in both groups (86.2 vs. 85.5%). After IPTW adjustment, the mean follow-up durations were 7.3 months and 6.6 months in the ARNI and ACEI/ARB groups, respectively. ARNI and ACEI/ARB users had a comparable risk of the composite clinical event (all-cause mortality or heart failure hospitalization) (hazard ratio [HR], 1.31; 95% confidence interval (CI) 0.91–1.88) and progression to dialysis (HR 1.04; 95% CI 0.54–2.03). In subgroup analysis, dialysis patients who used ARNIs were associated with higher incidence of heart failure hospitalization (subdistribution HR, 1.97; 95% CI 1.36–2.85).ConclusionsCompared with ACEIs or ARBs, ARNIs were associated with comparable clinical and renal outcomes in patients with HFrEF and advanced CKD (eGFR ≤ 30 mL/min/1.73 m2). In short-term, HF hospitalization may occur more frequently among ARNI users, especially in patients on dialysis.
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Underberg, Daniel L., Michael Jiang, SEAN DUNNE, Anjan Tibrewala, and Mayank Kansal. "Abstract 11693: Improving Angiotensin Receptor-Neprilysin Inhibitor Utilization for Veterans Admitted With Acute Decompensated Heart Failure: A Single-Center Experience." Circulation 146, Suppl_1 (November 8, 2022). http://dx.doi.org/10.1161/circ.146.suppl_1.11693.
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Objective: Improve angiotensin receptor-neprilysin inhibitor (ARNI) utilization among patients admitted with acute decompensated heart failure (HF) through a multidisciplinary quality improvement (QI) intervention. Background: ARNIs reduce mortality and hospitalizations for patients with HF and abnormal systolic function; current guidelines recommend them as first-line agents for Stage C HF. Inpatient initiation of ARNIs during an acute exacerbation is cost-effective and safe. Despite this, ARNI utilization remains low nationally and at our center. Methods: We implemented a multidisciplinary QI intervention at a large urban Veterans Affairs (VA) medical center. The intervention included electronic health record system redesign to provide clinical decision support, a new pharmacy-led screening process and recommendation system to the primary inpatient team, and an educational campaign. Our primary outcome metric was monthly ARNI initiation rate, defined as the number of new ARNI initiations divided by the number of eligible patients admitted for an acute HF exacerbation. We used a statistical process control (XmR) chart to measure change. Results: We observed a statistically significant, non-random improvement in mean monthly ARNI initiation rate from 8.4% pre-intervention to 35.7% post-intervention. An XmR chart is shown in Figure 1. Split limits analysis showed variation post-intervention was within statistical control, suggesting sustainable change. Conclusions: Our outcomes demonstrate successful implementation of a multidisciplinary intervention to improve ARNI utilization among patients admitted with acute decompensated HF at a large VA medical center. ARNI initiation rate increased significantly post-intervention, and the split limits analysis suggests that our results represent sustainable change. A longer period of data collection will be useful to assess HF readmission and mortality rates in response to this intervention.
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Cruz-Méndez, Hever, Elia Diego-García, Pablo Liedo, and Lorena Ruiz-Montoya. "Bioprospección de receptores de insulina a partir de ARN mensajero en Brevicoryne brassicae L. (Hemiptera: Aphididae)." ACTA ZOOLÓGICA MEXICANA (N.S.), July 25, 2022, 1–18. http://dx.doi.org/10.21829/azm.2022.3812513.
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La supresión de moléculas de ácido ribonucleico mensajero (ARNm) mediante ARN interferente (ARNi) se ha propuesto como método de control de insectos plagas. El ARNi impide el desarrollo morfológico y funcional de los insectos y se considera altamente específico. En este estudio se buscaron receptores de insulina (InR) en Brevicoryne brassicae L. (Hemiptera: Aphididae) a partir del ARNm de pulgones, como primer paso para el diseño posterior de ARNi dirigido a la supresión de InR. A partir del ácido desoxirribonucleico complementario (ADNc) y mediante PCR anidada, se amplificó la región correspondiente a InR con dos pares de cebadores diseñados para Nilaparvata lugens (Homoptera: Delphacidae). No se logró identificar InR, en su lugar se predice la presencia de la proteína receptora Dip2A de unión a folistatina (FS) debido a que comparten regiones proteicas similares con los InR, involucradas en la traducción de señales en los insectos. Se sugiere continuar con la búsqueda de InR específicos para el pulgón, así como posibles cebadores para regiones de Dip2A, para lograr un ARNi altamente específico.
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Tran, Jeffrey S., Macklin G. Loveland, Ahmad Alamer, Ileana L. Piña, and Nancy K. Sweitzer. "Clinical and Socioeconomic Determinants of Angiotensin Receptor-Neprilysin Inhibitor Prescription at Hospital Discharge in Patients With Heart Failure With Reduced Ejection Fraction." Circulation: Heart Failure 15, no. 11 (November 2022). http://dx.doi.org/10.1161/circheartfailure.121.009395.
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Background: Angiotensin receptor-neprilysin inhibitor (ARNI) prescription in the United States remains suboptimal despite strong evidence for efficacy and value in heart failure with reduced ejection fraction. Factors responsible for under prescription are not completely understood. Economic limitations may play a disproportionate role in reduced access for some patients. Methods: This is an analysis of the Get With The Guidelines-Heart Failure registry, supplemented with data from the Distressed Community Index. Data were fit to a mixed-effects regression model to investigate clinical and socioeconomic factors associated with ARNI prescription at hospital discharge. Missing data were handled by multilevel multiple imputation. Results: Of the 136 144 patients included in analysis, 12.6% were prescribed an ARNI at discharge. The dominant determinants of ARNI prescription were ARNI use while inpatient (odds ratio [OR], 72 [95% CI, 58–89]; P <0.001) and taking an ARNI before hospitalization (OR 9 [95% CI, 7–13]; P <0.001). Having an ACE (angiotensin-converting enzyme) inhibitor/angiotensin receptor blocker (ARB)/ARNI contraindication was associated with lower likelihood of ARNI prescription at discharge (OR, 0.11 [95% CI, 0.10–0.12]; P <0.001). Socioeconomic factors associated with lower likelihood of ARNI prescription included having no insurance (OR, 0.60 [95% CI, 0.50–0.72]; P <0.001) and living in a ZIP Code identified as distressed (OR, 0.81 [95% CI, 0.70–0.93]; P =0.010). The rate of ARNI prescription is increasing with time (OR, 2 [95% CI, 1.8–2.3]; P <0.001 for patients discharged in 2020 as opposed to 2017), but the disparity in prescription rates between distressed and prosperous communities appears to be increasing. Conclusions: Multiple medical and socioeconomic factors contribute to low rates of ARNI prescription at hospital discharge. Potential targets for improving ARNI prescription rates include initiating ARNIs during hospitalization and aggressively addressing patients’ access barriers with the support of inpatient social services and pharmacists.
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Dunlay, Shannon M., Jill Killian, Veronique L. Roger, Philip Schulte, Samuel Savitz, Saul Blecker, and Margaret M. Redfield. "Abstract 10068: Guideline Directed Medical Therapy in Newly Diagnosed Heart Failure with Reduced Ejection Fraction in the Community: Impact of Heart Failure Clinic." Circulation 144, Suppl_1 (November 16, 2021). http://dx.doi.org/10.1161/circ.144.suppl_1.10068.
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Introduction: Guideline-directed medical therapy (GDMT) dramatically improves outcomes in heart failure with reduced ejection fraction (HFrEF). Our goal was to examine GDMT use in community patients with newly diagnosed HFrEF. Methods: We performed a population-based, retrospective cohort study of all Olmsted County, Minnesota residents with newly diagnosed HFrEF (EF≤40%) 2007-2017. We excluded patients with contraindications to medication initiation (allergy, intolerance, heart rate<50 for beta blockers, SBP <80mm Hg for beta blockers, ACEi/ARB/ARNI; high creatinine (>3 mg/dL ACEi/ARB/ARNI, >2.5 men or >2.0 mg/dL women for mineralocorticoid receptor antagonists, MRAs) or hyperkalemia (potassium >5 meQ/L for ACEi/ARB/ARNI, MRA). We examined use and peak dose achieved for beta blockers, HF beta blockers (metoprolol succinate, carvedilol, bisoprolol), ACEi/ARB/ARNI, and MRA in the first year after HFrEF diagnosis. We used logistic regression to evaluate predictors of GDMT use. Results: From 2007-2017, 1160 patients were diagnosed with HFrEF (mean age 69.7 years, 65.6% men). Most eligible patients received beta blockers (92.1%) and ACEi/ARB/ARNI (86.5%) in the first year after HFrEF. However, only 63.6% of patients were treated with a HF beta blocker, and most did not receive MRAs (82.6%). The percentage of treated patients reaching medication target doses was 20.5% for HF beta blockers, 25.3% for ACEi/ARB/ARNI, and 11.2% for MRA. Compared to patients not seen in an HF clinic, patients seen in an HF clinic (n=380, 32.8%) were at greater odds of receiving beta blockers (OR 3.85, 95% CI 1.79-8.33); HF beta blockers (OR 3.85, 95% CI 2.63-5.26); ACEi/ARB/ARNIs (OR 3.85, 95% CI 2.17-6.67); and MRAs (OR 3.03, 95% CI 2.08-4.35). Other independent predictors of GDMT use included younger age (beta blockers, ACEi/ARB/ARNI), male gender (MRAs), higher SBP (beta blockers, ACEi/ARB/ARNI), lower EF (HF beta blockers), higher BMI (MRAs), and diabetes (ACEi/ARB/ARNI, p<0.05 for each). Conclusions: In this population-based study, most patients with newly diagnosed HFrEF received beta blockers and ACEi/ARB/ARNIs, but goal doses were usually not achieved. GDMT use was much higher in patients referred to an HF clinic.
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Chapman, Brittany, Anne S. Hellkamp, Laine E. Thomas, Nancy M. Albert, Javed Butler, J. Herbert Patterson, Adrian F. Hernandez, et al. "Angiotensin Receptor Neprilysin Inhibition and Associated Outcomes by Race and Ethnicity in Patients With Heart Failure With Reduced Ejection Fraction: Data From CHAMP‐HF." Journal of the American Heart Association 11, no. 12 (June 21, 2022). http://dx.doi.org/10.1161/jaha.121.022889.
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Background There are limited data on the use of angiotensin receptor neprilysin inhibitors (ARNIs) in minority populations with heart failure (HF) with reduced ejection fraction. We used data from the CHAMP‐HF (Change the Management of Patients With Heart Failure) registry to evaluate ARNI initiation and associated changes in health status and clinical outcomes across different races and ethnicities. Methods and Results CHAMP‐HF was a prospective, observational registry of US outpatients with chronic HF with reduced ejection fraction. We compared patients starting ARNI with patients not starting ARNI using a propensity‐matched analysis. Patients were grouped as Hispanic, non‐Hispanic Black, non‐Hispanic White, or non‐Hispanic other individuals, where “non‐Hispanic other” consists of all patients who did not identify as Hispanic, Black, or White. Health status was assessed using the 12‐item Kansas City Cardiomyopathy Questionnaire. Outcomes were analyzed with multivariable models that included race and ethnicity, ARNI initiation, and an interaction term between race and ethnicity and ARNI initiation. Cox proportional hazards models were used for death/HF hospitalization, and multiple regression was used for change in Kansas City Cardiomyopathy Questionnaire score. The analysis included 1516 patients, with 758 patients in each group (ARNI and no ARNI). Changes in Kansas City Cardiomyopathy Questionnaire score after ARNI initiation were similar among all race and ethnicity groups (mean [SD], non‐Hispanic White individuals, 3.5 [19.0]; non‐Hispanic Black individuals, 2.0 [17.0]; non‐Hispanic other individuals, 5.5 [20.3]; and Hispanic individuals, 3.2 [20.1]), with no statistically significant interaction between race and ethnicity and ARNI initiation ( P =0.21). There was similarly no statistically significant interaction between race and ethnicity and ARNI initiation for HF hospitalization ( P =0.82) or all‐cause mortality ( P =0.92). Conclusions In a large registry of outpatients with HF with reduced ejection fraction, the association between ARNI initiation and outcomes did not differ by race and ethnicity. These data support the use of ARNI therapy for chronic HF with reduced ejection fraction irrespective of race and ethnicity.
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Ali, Hyeon‐Ju Ryoo, Jerome Thomas, Sandeep Sahay, and Ashrith Guha. "Management of pulmonary hypertension associated with valvular heart disease with angiotensin‐receptor neprilysin inhibitor." Pulmonary Circulation 13, no. 4 (October 2023). http://dx.doi.org/10.1002/pul2.12303.
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AbstractPulmonary hypertension secondary to left‐sided valvular disease (VHD‐PH) is associated with high morbidity and mortality. Angiotensin‐receptor neprilysin inhibitor (ARNI) is a novel pharmacotherapy, which reduces afterload with natriuresis and peripheral vasodilation. Our cases demonstrate that ARNI may also have a role in the treatment of combined pre‐ and postcapillary pulmonary hypertension that is independent of its effect on pulmonary capillary wedge pressure and cardiac output. Future prospective trials are needed to evaluate role of ARNIs in treatment of VHD‐PH.
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Zipkin, Ronnie, J. Aaron Barnes, Anna Tosteson, Thomas A. Gaziano, and Lauren Gilstrap. "Abstract 11131: Discharge on Sacubitril/Valsartan vs. ACEi/ARB in Older Patients with HFrEF: A Decision Analysis Approach." Circulation 144, Suppl_1 (November 16, 2021). http://dx.doi.org/10.1161/circ.144.suppl_1.11131.
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Introduction: Based on the results of PARADIGM-HF and PIONEER-HF, angiotensin-receptor neprilysin inhibitors (ARNI) offer improved survival and lower readmission rates for HFrEF compared to angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). However, there is concern that increased hypotension and higher drug costs may limit the effectiveness of ARNIs in clinical practice, especially among older adults with Part D prescription coverage. The aim of this study is to use decision analytic modeling to estimate the association between discharge on ARNI vs. ACEi/ARB and patient outcomes, and then determine if it varies by age. Methods: We then used a 2-state absorbing Markov chain model with a 1-month cycle length to simulate 5-year survival for patients discharged on ARNI or ACEi/ARB, accounting for the risks of death and readmission, estimated from trials, as well as the risk of in-hospital mortality, drug switching, and discontinuation, estimated from Medicare claims data. In the model, the weighted averages for mortality and readmission reduction were estimated published risk reductions from the PIONEER-HF trials (first two months) and PARADIGM-HF (subsequent 8 months) trials. Results: Across all age groups, patients discharged on ARNI had higher 5-year survival compared to patients discharged on ACEi/ARB ( Table 1 ). Moreover, the absolute and relative benefit of ARNI over ACEi/ARB, even after accounting for drug discontinuation and switching, was similar across age groups. The number needed to treat (NNT) with ARNI rather than ACEi/ARB to prevent 1 death over 5 years ranged from 56-63. Conclusions: There is a small, but clinically significant, survival benefit to discharge on ARNI vs. ACEi/ARB across all age groups, even after accounting for drug switching and discontinuation. Additional work is needed to determine if there is additional heterogeneity of treatment effect in subgroups of high-risk, older adults.
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Park, Hyuk Kyoon, Jong Sung Park, Myeong Seop Kim, Eunkyu Lee, Hyohun Choi, Yoon Jung Park, Bo Eun Park, et al. "Long‐term impact of angiotensin receptor‐neprilysin inhibitor based on short‐term treatment response in heart failure." ESC Heart Failure, September 13, 2023. http://dx.doi.org/10.1002/ehf2.14505.
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AbstractAimsThe long‐term effect of angiotensin receptor–neprilysin inhibitor (ARNI) remains uncertain in patients who have experienced improvements in left ventricular (LV) systolic function or significant LV reverse remodelling following a certain period of treatment. It is also unclear how ARNI performs in patients who have not shown these improvements. This study aimed to assess the impact of prolonged ARNI use compared with angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) in patients with and without significant treatment response after 1 year of heart failure (HF) treatment.Methods and resultsThe present study enrolled patients with HF with reduced ejection fraction (HFrEF) who were treated with either ARNI or ACEIs/ARBs within 1 year of undergoing index echocardiography. After 1 year of treatment, patients were reclassified into the following groups: (i) patients with HF with improved ejection fraction and persistent HFrEF and (ii) patients with and without LV reverse remodelling based on the follow‐up echocardiography. The effect of ARNI versus that of ACEIs/ARBs in each group was assessed from the time of categorizing into new groups using the composite event of all‐cause mortality and HF hospitalization. A total of 671 patients with HFrEF (age, 66.4 ± 14.1 years; males, 66.8%) were included, and 133 (19.8%) composite events of death and rehospitalization for HF were observed during the follow‐up (median follow‐up, 44 [interquartile range, 34–51] months). ARNI had a significantly lower event rate than ACEIs/ARBs in patients with HF with improved ejection fraction (7.0% vs. 30.4%, P = 0.020) and those with persistent HFrEF (17.6% vs. 49.7%, P < 0.001). Irrespective of whether patients exhibited LV reverse remodelling (15.8% vs. 31.1%, P = 0.001) or not (15.0% vs. 54.9%, P < 0.001), ARNIs were associated with a significantly lower event rate than ACEIs/ARBs.ConclusionsRegardless of significant treatment response measured by either LVEF or LV reverse remodelling after 1 year of treatment, the extended utilization of ARNI demonstrated a more favourable prognosis than that of ACEIs/ARBs in patients with HFrEF.
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Pun, Chon Kit, Ching-Chih Chang, Chiao-Lin Chuang, Hui-Chun Huang, Shao-Jung Hsu, Yi-Hsiang Huang, Ming-Chih Hou, and Fa-Yauh Lee. "Dual angiotensin receptor and neprilysin inhibitor reduced portal pressure through peripheral vasodilatation and decreasing systemic arterial pressure in cirrhotic rats." Journal of the Chinese Medical Association, July 18, 2023. http://dx.doi.org/10.1097/jcma.0000000000000959.
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Background: Portal hypertension develops along with the progression of liver cirrhosis. Natriuretic peptides have been shown to reduce portal pressure but concomitantly activate the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) upregulate natriuretic peptides and avoid the adverse effects of RAAS activation. ARNIs have been shown to reduce portal pressure in rats with prehepatic portal hypertension, which involves relatively little liver injury. This study aimed to evaluate the relevant effects of an ARNI in rats with both liver cirrhosis and portal hypertension. Methods: Male Sprague-Dawley rats received common bile duct ligation to induce liver cirrhosis and portal hypertension. Sham-operated rats served as surgical controls. All rats were randomly allocated into three groups to receive distilled water (vehicle), LCZ696 (an ARNI), or valsartan for 4 weeks. Portal hypertension and relevant derangements were assessed after treatment. Results: Portal hypertension and hyperdynamic circulation developed in the cirrhotic rats. In the rats with cirrhosis and portal hypertension, both LCZ696 and valsartan reduced portal hypertension, mean arterial pressure, and systemic vascular resistance. The decrease in portal pressure was highly associated with the reduction in arterial pressure and systemic vascular resistance. Blood flow in hepatic, splanchnic and portosystemic collateral systems was not altered. LCZ696 did not significantly influence liver injury or plasma cytokine levels. Liver fibrosis and splanchnic angiogenesis were not affected. Conclusion: ARNI treatment exerted portal pressure lowering effects via peripheral vasodilatation and decreasing systemic arterial pressure in the rats with liver cirrhosis and portal hypertension. Caution should be taken when using ARNIs in liver cirrhosis.
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Ohnewein, B., Z. Shomanova, P. Jirak, A. Topf, E. J. Froeb, C. Pogoda, C. Granitz, et al. "Effects of angiotensin receptor-neprilysin inhibitors (ARNIs) on the glucose and fat metabolism biomarkers leptin and fructosamin." European Heart Journal 43, Supplement_2 (October 1, 2022). http://dx.doi.org/10.1093/eurheartj/ehac544.974.
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Abstract Background Heart Failure with reduced ejection fraction (HFrEF) has a life time risk about 20% among adults aged 40 years or older and a 5-year mortality rate about 60% [1,2]. However novel therapies have shown to improve this outcome. One novel agent are angiotensin receptor-neprilysin inhibitors (ARNIs) that increase the BNP levels via inhibiting neprilsyin [3]. This has beneficial effects on heart failure by reducing preload, inflammation and fibrosis. Neprilysin also interacts with leptin and is known to correlate with the incidence and progression of heart failure if chronically elevated [4]. Furthermore beneficial affects of ARNI therapy on glucose metabolism were reported in a post-hoc analysis of the PARADIGM-HF trial [5]. In this study we aim to investigate the effect of ARNI therapy on the fat metabolism markers leptin and on the glucose metabolism marker fructosamin. Methods In total, we included 74 patients with HFrEF with ischemic (N=37) and non-ischemic (n=37) origin in the present study. The mean NYHA class was II–III, the mean BMI 28 (SD 6.3). Patients had well established heart failure therapy before starting ARNI therapy with sacubitril/valsartan. 88% of patients were on ACE-inhibitors, 86% on beta blockers and 68% on mineralocorticoid receptor antagonists. Serum samples were obtained and analyzed for leptin, fructosamin and pBNP before and 3–6 month after ARNI therapy. The clinical parameters LVEF and NYHA class were assessed before and 3–6 month after ARNI therapy. Results Baseline leptin level was 15.0 (SD 17.2), baseline fructosamin level was 370.1 (SD 167.7) and baseline pBNP level was 1494.9 (SD 1281.4). Under therapy a significant improvement of ejection fraction from 29,8% to 37,5% (7,7 SD 8,5 P≤0.001), an improvement of NYHA stadium from 2.46 (SD 0.62) to 1.96 (SD 0.63, p=0.005) and a significant decrease of pBNP (562.1 SD 1256.4, p=0.018) was found. Along with that, a significant increase in leptin levels (3.6 SD 8.85, p=0.012) and a significant increase in fructosamine levels (93.5 SD 160.6, p=0.013) was shown. Conclusion Under therapy with ARNI we showed a sufficient therapy response with improvement of ejection fraction and decrease of pBNP in line with literature. Surprisingly metabolism biomarkers did significantly worsen under the first three to six month after new ARNI therapy. To distinguish between a side effect of ARNI therapy or consequence of heart failure itself further investigations are needed. Funding Acknowledgement Type of funding sources: None.
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Tsukamoto, Shunichiro, Hiromichi Wakui, Tatsuki Uehara, Yuka Shiba, Kengo Azushima, Eriko Abe, Shohei Tanaka, et al. "Combination of Sacubitril/Valsartan and Blockade of the PI3K Pathway Enhanced Kidney Protection in a Mouse Model of Cardiorenal Syndrome." European Heart Journal Open, September 29, 2023. http://dx.doi.org/10.1093/ehjopen/oead098.
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Abstract Background Angiotensin receptor-neprilysin inhibitor (ARNI) is an established treatment for heart failure. However, whether ARNI has renoprotective effects beyond renin-angiotensin system inhibitors alone in cardiorenal syndrome (CRS) has not been fully elucidated. Here, we examined the effects of ARNI on the heart and kidneys of CRS model mice with overt albuminuria and identified the mechanisms underlying ARNI-induced kidney protection. Methods C57BL6 mice were subjected to chronic angiotensin II infusion, nephrectomy, and salt loading (ANS); they developed CRS phenotypes and were divided into the vehicle treatment (ANS-vehicle), sacubitril/valsartan treatment (ANS-ARNI), and two different doses of valsartan treatment (ANS-VAL-M, ANS-VAL-H) groups. Four weeks after treatment, the hearts and kidneys of each group were evaluated. Results The ANS-vehicle group showed cardiac fibrosis, cardiac dysfunction, overt albuminuria, and kidney fibrosis. The ANS-ARNI group showed a reduction in cardiac fibrosis and cardiac dysfunction compared with the valsartan treatment groups. However, regarding the renoprotective effects characterized by albuminuria and fibrosis, ARNI was less effective than valsartan. Kidney transcriptomic analysis showed that the ANS-ARNI group exhibited a significant enhancement in the phosphoinositide 3-kinase (PI3K)-AKT signaling pathway compared with the ANS-VAL-M group. Adding PI3K inhibitor treatment to ARNI ameliorated kidney injury to levels comparable with those of ANS-VAL-M while preserving the superior cardioprotective effect of ARNI. Conclusions PI3K pathway activation has been identified as a key mechanism affecting remnant kidney injury under ARNI treatment in CRS pathology, and blockading the PI3K pathway with simultaneous ARNI treatment is a potential therapeutic strategy for treating CRS with overt albuminuria.
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Omar, M., J. Hempel Larsen, J. Jensen, C. Kistorp, L. Videbaek, M. Kjaer Poulsen, F. Gustafsson, L. Koeber, M. Schou, and J. Eifer Moeller. "Effect of empagliflozin in hfref patients treated with angiotensin receptor neprilysin inhibitor an analysis of EMPIRE HF." European Heart Journal 42, Supplement_1 (October 1, 2021). http://dx.doi.org/10.1093/eurheartj/ehab724.0800.
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Abstract Introduction Inhibition of neprilysin/valsartan (ARNi) or sodium glucose cotransporter 2 (SGLT2) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) has been shown to reduce the risk of Cardiovascular death and hospitalization for HF. Recent trails suggested that SGLT2 reduces the risk for cardiovascular death or hospitalization for HF, regardless of underlying ARNi treatment and that the effect may even be greater in those receiving the combination. Whether there exist an interaction between effect of ARNi and SGLT2 on functional endpoints related to mechanism of action is unknown. Purpose This post-hoc analysis of the randomized double-blinded Empire HF trial evaluated the influence of ARNi on the effect of the SGLT2 Empagliflozin on N-terminal prohormone B-type natriuretic peptide (NT-proBNP), pulmonary capillary wedge pressure (PCWP), Left ventricular end-systolic and end-diastolic volumes index; (LVESVI) (LVEDVI), left atrial volume index (LAVI), Left ventricular ejection fraction (LVEF), and Kansas City Cardiomyopathy Questionnaire (KCCQ) HFrEF patients. Methods Empire HF trial randomized 190 patients with HFrEF (LVEF ≤40%) to placebo or empagliflozin (10 mg/day), on top of recommended treatment for HFrEF, for 12 weeks of treatment. A total of 58 (31%) received ARNi at baseline and no patients initiated ARNi during study period. Results Patients on ARNi were well-treated with a similar baseline characteristic as those who were not treated with ARNi (Table 1). Patients with ARNi had a lower systolic blood pressure (P=0.01), with a higher NT-proBNP (P<0.001) when compared with those not receiving ARNi. When compared to placebo, empagliflozin did not reduce the ratio of change of NT-proBNP with or without ARNi (0.94 [95% CI, 0.75 to 1.19] pg/ml; P=0.62) and (1.02 [95% CI, 0.86 to 1.22] pg/ml; P=0.78), respectively, adjusted (age, atrial fibrillation) interaction P=0.57. Empagliflozin reduced PCWP regardless of ARNi treatment (with ARNi; −4.9 [95% CI, −9.1 to −0.6] mmHg; P=0.02) and (without ARNi; −2.1 [95% CI, −3.8 to −0.4] mmHg; P=0.01), adjusted interaction P=0.20. Overall, empagliflozin was associated with a reduction in LVESVI, LVEDVI, and LAVI volumes, but no effect on LVEF. However, Empagliflozin combined with ARNi at baseline, significantly reduced LVEDVI (−11.2 [95% CI, −21.2 to −1.2] ml/m2; P=0.03), but not without ARNI (−2.9 [95% CI, −8.7 to 2.9] ml/m2; P=0.32), adjusted interaction P=0.13. Treatment-by-subgroup interaction P-values for LVESVI, LAVI, and LVEF analysis were >0.05 (Figure 1). KCCQ total symptom score were significantly increased in those not receiving ARNi (5.4 [95% CI, 1.1 to 9.6]; P=0.013), but not with ARNi (−4.0 [95% CI, −10.3 to 2.3]; P=0.22), adjusted P=0.02. Conclusion In this post hoc analysis the effects on empagliflozin to reduce PCWP and LV volumes were not diminished in patients receiving ARNi, however KCCQ change were diminished in patients receiving ARNi. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): This work was supported by the Danish Heart Foundation [grant numbers 17-R116-A7714-22076, 18-R124-A8573-22107]; Steno Diabetes Center Odense, Denmark [grant number 3363] and A.P. Møller Foundation for the Advancement of Medical Science [grant number 17-L-0339]. Table 1. Baseline characteristicsFigure 1. Change in echo variables +/− ARNi
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Tsukamoto, Shunichiro, Tatsuki Uehara, Kengo Azushima, Hiromichi Wakui, and Kouichi Tamura. "Updates for Cardio‐Kidney Protective Effects by Angiotensin Receptor‐Neprilysin Inhibitor: Requirement for Additional Evidence of Kidney Protection." Journal of the American Heart Association 12, no. 8 (April 18, 2023). http://dx.doi.org/10.1161/jaha.122.029565.
Full textAbstract:
The incidence of heart failure and chronic kidney disease is increasing, and many patients develop both diseases. Angiotensin receptor‐neprilysin inhibitor (ARNI) is a promising therapeutic candidate for both diseases. ARNI has demonstrated superior cardioprotective effects compared with renin–angiotensin system inhibitors (RAS‐Is) in large clinical trials such as the PARADIGM‐HF (Prospective Comparison of ARNI With ACEI [Angiotensin‐Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. It has also been suggested that ARNI can provide renoprotective effects beyond those of RAS‐Is in patients with HF. ARNI might have beneficial effects on the kidneys because of its ability to improve cardiac function in patients with heart failure and affect renal hemodynamics by enhancing the effects of hormones such as natriuretic peptide. In contrast, in the PARADIGM‐HF trial, ARNI was associated with more albuminuria compared with RAS‐I; thus, it is unclear whether long‐term ARNI therapy has renoprotective effects. Additionally, ARNI did not provide renoprotective effects beyond RAS‐I in patients with chronic kidney disease in the UK HARP‐III (United Kingdom Heart and Renal Protection‐III) trial. In other words, the patient population in which ARNI is more renoprotective than RAS‐I might be limited. Collectively, ARNI may have renoprotective effects in addition to cardioprotective effects, but the evidence to date is applicable only to heart failure. Theoretically, given the molecular mechanism of ARNI, it could also be renoprotective in conditions such as nephrosclerosis, which has low risks of albuminuria and reduced kidney perfusion, but the evidence for such effects is lacking. Further research is needed to clarify whether ARNI therapy is an acceptable treatment strategy for renal protection.
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Karabulut, Umut, Kudret Keskin, Dilay Karabulut, Ece Yiğit, and Zerrin Yiğit. "Effect of Sacubitril/Valsartan Combined with Dapagliflozin on Long-Term Cardiac Mortality in Heart Failure with Reduced Ejection Fraction." Angiology, September 24, 2021, 000331972110473. http://dx.doi.org/10.1177/00033197211047329.
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The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II–IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16–3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) ( P = .01). Dapagliflozin [Hazard Ratio (HR) [95% Confidence Interval (CI)] = .29 [.10–.77]; P = .014] and left ventricular ejection fraction (LVEF) [HR (95% CI) = .89 (.85–.93); P < .001] were found to be independent predictors of cardiac mortality. Our study showed a significant reduction in cardiac mortality with ARNI and dapagliflozin combination therapy compared with ARNI monotherapy.
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Kim, Hyue Mee, In-Chang Hwang, Wonsuk Choi, Yeonyee E. Yoon, and Goo-Yeong Cho. "Combined effects of ARNI and SGLT2 inhibitors in diabetic patients with heart failure with reduced ejection fraction." Scientific Reports 11, no. 1 (November 16, 2021). http://dx.doi.org/10.1038/s41598-021-01759-5.
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AbstractAngiotensin receptor-neprilysin inhibitor (ARNI) and sodium–glucose co-transporter-2 inhibitor (SGLT2i) have shown benefits in diabetic patients with heart failure with reduced ejection fraction (HFrEF). However, their combined effect has not been revealed. We retrospectively identified diabetic patients with HFrEF who were prescribed an ARNI and/or SGLT2i. The patients were divided into groups treated with both ARNI and SGLT2i (group 1), ARNI but not SGLT2i (group 2), SGLT2i but not ARNI (group 3), and neither ARNI nor SGLT2i (group 4). After propensity score-matching, the occurrence of hospitalization for heart failure (HHF), cardiovascular mortality, and changes in echocardiographic parameters were analyzed. Of the 206 matched patients, 92 (44.7%) had to undergo HHF and 43 (20.9%) died of cardiovascular causes during a median 27.6 months of follow-up. Patients in group 1 exhibited a lower risk of HHF and cardiovascular mortality compared to those in the other groups. Improvements in the left ventricular ejection fraction and E/e′ were more pronounced in group 1 than in groups 2, 3 and 4. These echocardiographic improvements were more prominent after the initiation of ARNI, compare to the initiation of SGLT2i. In diabetic patients with HFrEF, combination of ARNI and SGT2i showed significant improvement in cardiac function and prognosis. ARNI-SGLT2i combination therapy may improve the clinical course of HFrEF in diabetic patients.
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Wang, Xiaobo, Jun Pu, Guixia Wang, Hui Xu, Liming Liu, Zhen Li, Ruijie Qin, et al. "Efficacy and safety analysis of angiotensin receptor neprilysin inhibition(ARNI)in patients with heart failure: a real-world retrospective study." BMC Cardiovascular Disorders 23, no. 1 (July 10, 2023). http://dx.doi.org/10.1186/s12872-023-03374-w.
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Abstract Background In a large randomized controlled trial (PARADIGM-HF), ARNI has been shown to significantly reduce cardiovascular mortality and hospitalization for patients with reduced ejection fraction in heart failure. This study analyzed the efficacy and safety of ARNI on the basis of various types of heart failure patients in southwestern Sichuan Province. Methods This study included patients with heart failure who were treated at the Affiliated Hospital of North Sichuan Medical College from July 2017 to June 2021. This study analyzed the efficacy and safety of ARNI in the treatment of heart failure, and analyzed the risk factors for readmission after ARNI treatment. Results After propensity score matching, a total of 778 patients were included in the study. The readmission rate for heart failure in patients treated with ARNI (8.7%) was significantly lower than that in the standard treatment group (14.5%) (P = 0.023). Both the proportion of patients with increased LVEF and with decreased LVEF were higher in the ARNI treatment group than in the conventional therapy group. Compared with receiving standard medical treatment, combined ARNI treatment resulted in a greater reduction in SBP (-10.00, 95%CI: -24.00-1.50 vs. -7.00, 95%CI: -20.00-4.14; P = 0.016) in HF patients. Combination ARNI therapy did not increase the risk of adverse events. The study found that age (> 65 vs. ≤65 years) (OR = 4.038, 95%CI: 1.360-13.641, P = 0.013) and HFrEF (OR = 3.162, 95%CI: 1.028–9.724, P = 0.045) were independent predictors of readmission in HF patients treated with ARNI. Conclusion Patients with heart failure treated with ARNI can improve clinical symptoms and reduce the risk of readmitted hospital admission. Age > ~ 65 years and HFrEF were independent predictors of readmission in HF patients treated in ARNI group.
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KOMMU, SHARATH. "Abstract 12247: The Effect of Angiotensin Receptor-Neprilysin Inhibitor With Sodium-Glucose Cotransporter 2 Inhibitor versus Angiotensin Receptor-Neprilysin Inhibitor Without Sodium-Glucose Cotransporter 2 Inhibitor on Heart Failure Outcomes in Patients With Heart Failure With Reduced Ejection Fraction." Circulation 148, Suppl_1 (November 7, 2023). http://dx.doi.org/10.1161/circ.148.suppl_1.12247.
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Background: Angiotensin receptor-neprilysin inhibitor (ARNI) improves heart failure outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Similarly, sodium-glucose cotransporter 2 (SGLT2) inhibitors have also shown significant beneficial effects in this patient population. It is unclear if adding SGLT2 inhibitors to patients already using ARNI-containing regimen will have additional benefits in improving heart failure outcomes in patients with HFrEF. Methods: PubMed and MEDLINE search was performed using the search words – ARNI, SGLT2 inhibitor, and heart failure. Among the studies identified, we looked for randomized controlled, prospective, and retrospective studies on HFrEF that included patient groups using ARNI with SGLT2 inhibitors and ARNI without SGLT2 inhibitors and had heart failure outcomes. We identified three studies and performed a meta-analysis. Results: A total of 671 patients in the treatment group and 808 patients in the placebo group are included in our meta-analysis. The heart failure outcome analyzed is the composite of hospitalization for heart failure and cardiovascular death. Among the patients using ARNI without SGLT2 inhibitors, the outcome occurred in a total of 215 out of 808 patients (26.61%). In comparison, it occurred in 114 out of 671 patients (16.99%) among those who are on both ARNI and SGLT2 inhibitors. This study shows that there is a significant improvement in this heart failure outcome in patients with HFrEF taking an SGLT2 inhibitor and ARNI-containing regimen compared to those taking ARNI without an SGLT2 inhibitor with a relative risk (RR) of 0.67 and 95% confidence interval (CI) of 0.55 to 0.83 (p=0.0001). Conclusion: Though ARNI and SGLT2 inhibitors individually are known to improve heart failure outcomes, adding an SGLT2 inhibitor to ARNI significantly improves the heart failure outcome of the composite of hospitalization for heart failure and cardiovascular death in patients with HFrEF.
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Tsukamoto, Shunichiro, Hiromichi Wakui, Tatsuki Uehara, Kengo Azushima, and Kouichi Tamura. "Abstract A3: Possible Differential Effects Of Angiotensin Receptor-neprilysin Inhibitor And Angiotensin Receptor Blocker Against Hypertension And Cardiorenal Injury In A Mouse Model Of Cardiorenal Syndrome." Hypertension 79, Suppl_1 (September 2022). http://dx.doi.org/10.1161/hyp.79.suppl_1.a3.
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Objective: Angiotensin receptor-neprilysin inhibitors (ARNI) are potential therapeutic candidates for the treatment of cardiorenal syndrome (CRS). Although evidence is accumulating on the therapeutic effects of ARNI for heart failure and hypertension, the effects of ARNI on kidney disease or CRS are controversial. Here, we assessed the hypothesis that ARNI has poor renal protective effect beyond its antihypertensive effect, in contrast to its promised cardioprotective effect, by using the ANS [Ang II (A) + nephrectomy (N) + saline (S)] mice, which is the CRS model. Method: C57BL/6 mice were divided into 5 groups (N = 5-6): Control (sham operation) group, ANS (ANS + vehicle treatment) group, Val M [ANS + moderate dose of valsartan treatment (30 mg/kg/day)] group, ARNI [ANS + sacubitril/valsartan treatment (60 mg/kg/day)] group, and Val H [ANS + high dose of valsartan treatment (60 mg/kg/day)] group. Sacrifice was performed after 4 weeks, and various analyses were conducted. Results: ARNI, Val M, and Val H groups attenuated the elevation of blood pressure (BP) in ANS mice (BP [mean ± standard error (SEM)] [mmHg]: ANS, 164 ± 3; ARNI, 133 ± 4; Val M, 143 ±1; Val H, 129 ± 2). Regardless of the strength of the antihypertensive effect, the ARNI group was most effective in preventing the decrease in cardiac contraction and cardiac fibrosis in ANS mice. However, the ARNI group was insufficient to suppress urinary albumin excretion (UAE) (UAE [mean ± SEM] [μg]; ANS, 5351 ± 2391; ARNI, 1169 ± 700) and renal fibrosis in ANS mice. Both valsartan groups suppressed UAE in ANS mice (UAE [mean ± SEM] [μg]; Val M, 243 ± 141; Val H, 305 ± 179), as well as renal fibrosis and glomerular swelling. In addition, the results of kidney RNA sequencing analysis showed that the receptor for advanced glycation end-products (RAGE) signaling pathway was activated in the kidney of ARNI group compared with the Val M and Val H groups. Conclusions: The ARNI group showed better cardioprotective effects than valsartan treatment groups, but not sufficient kidney protection. These results suggested that the relationship between the antihypertensive effects and the organ protective effects of cardiorenal injury in CRS pathology may be different between angiotensin II receptor blocker (ARB) and ARNI.
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Nathaniel, Sangeetha D., Shane McGinty, David G. Edwards, William B. Farquhar, Melissa A. Witman, Vinay Hosmane, and Megan M. Wenner. "Abstract P097: Angiotensin Receptor Neprilysin Inhibition Improves Arterial Stiffness And Endothelial Function In Heart Failure With Reduced Ejection Fraction." Hypertension 76, Suppl_1 (September 2020). http://dx.doi.org/10.1161/hyp.76.suppl_1.p097.
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The mechanisms for the benefits of Angiotensin Receptor Neprilysin inhibitor (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure (BP) reduction. Vascular function, a prognostic marker in HFrEF, improves with ARNi in animal models. Improvements in vascular function may contribute to benefits from ARNi in HFrEF; however, this has yet to be demonstrated in humans. The purpose of the study was to test the hypothesis that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. Methods: HFrEF participants with NYHA class II-III were enrolled from local cardiology clinics and completed experimental visits at baseline and 12 weeks later: 13 participants were prescribed ARNi by their cardiologist [62±10 years, Men: 10, BMI: 30±5 kg/m 2 , EF: 28±6 %; Non-ischemic cardiomyopathy (NICM): 8], 10 participants continued on conventional treatment [CON: 60±7 years, Men: 6, BMI: 31±6 kg/m 2 , EF: 31±5 % and NICM: 4; all P=NS]. During each experimental visit, arterial stiffness was assessed via carotid-femoral pulse wave velocity (PWV; Sphygmocor PVx system) and endothelial function by brachial artery flow-mediated dilation (FMD) using standard techniques. Statistical analyses were performed using 2x2 repeated-measures ANOVA. Results: Baseline mean BP (MAP) was similar between ARNi (93±14 mmHg) and CON (85 ± 10 mmHg; P=0.13); MAP tended to decrease after 12 weeks of ARNi (88 ± 11 mmHg; P=0.08) but not CON (90 ± 17 mmHg; P=0.14) (ANOVA interaction P=0.03). PWV tended to be higher at baseline in ARNi (8.8 ± 2.5 m/s) compared to CON (7.0 ± 2.5 m/s; P=0.09); PWV decreased after 12 weeks of ARNi (7.0 ± 1.7 m/s; P<0.01) and was unchanged in CON (7.4 ± 2.4 m/s; P=0.33) (ANOVA interaction P<0.01). When controlling for MAP, the effect of ARNi on PWV remained (P<0.01). At baseline, FMD was similar between ARNi (2.81 ± 2.05%) and CON (4.75 ± 3.75%; P=0.13); however, FMD increased after 12 weeks of ARNi (5.73 ± 1.87%; P<0.001) but not in CON (5.37 ± 3.38%; P=0.33) (ANOVA time P<0.001, interaction P=0.01). Conclusion: ARNi improves arterial stiffness and endothelial function in HFrEF. Understanding the mechanisms of ARNi in HFrEF is crucial as it may pave the way for better interventions in other cardiovascular diseases.
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Ephrem, Georges, Jonathan C. McCollum, Deborah Green-Hess, Stephen G. Sawada, Maya Guglin, and Roopa A. Rao. "Abstract 15381: Subjective and Objective Impact of Angiotensin Receptor-neprilysin Inhibitor on Systemic Right Ventricle Patients." Circulation 142, Suppl_3 (November 17, 2020). http://dx.doi.org/10.1161/circ.142.suppl_3.15381.
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Introduction: Adult Congenital Heart Disease (ACHD) patients have increased mortality and morbidity from heart failure. Angiotensin receptor-Neprilysin Inhibitors (ARNI) have emerged as a standard of therapy for adults with heart failure. These medicines have not been studied in ACHD patients. Hypothesis: ARNIs are associated with subjective and objective improvements in systemic right ventricle (SRV) patients. Methods: Eighteen SRV patients were prescribed ARNI at our institution in the last 3 years. Data including demographics, medical history, New York Heart Association functional class (NYHA FC), labs, 3D imaging, echocardiograms, cardiopulmonary stress test (CPET), and hospitalization were obtained by retrospective electronic chart review. Statistical analysis was performed using paired t and Wilcoxon rank sum tests. Results: Eighteen SRV patients (mean age 40 years, 72% male) were treated with ARNI (median 13 months) and conventional therapy (beta blocker (83%), loop diuretic (89%), antiarrhythmics (33%), and anticoagulation (50%)). Baseline data include: Mean blood pressure 118/75 mmHg, pulse 75 bpm, creatinine 0.86 mg/dL, potassium 4 meq/L, B-type natriuretic peptide (BNP) 322 pg/mL, and NT-Pro BNP 1091 pg/mL. Nine patients were NYHA FC 2, 7 FC 3, and 2 FC 4. High dose was achieved in 3 (17%) patients, and moderate in 3 (17%). CPET and imaging data were: VO2 18 mL/kg/min, VE/VCO2 38, RVEF 32%, FAC 21%, significant TR (12.5% moderate, and 12.5% severe) and TAPSE 9.4. There was no statistically significant difference pre vs post-ARNI in blood pressure, labs (creatinine, potassium, BNP and NT-ProBNP), or testing (VO2 18 vs 17, p=0.432; VEVCO2 38 vs 39, p=0.850; RVEF 32 vs 32%, p=0.648; FAC 18 vs 21%, p=0.489; TR p=0.317; and TAPSE 9.2 vs 9.1, p=0.906). There was a statistically significant improvement in median NYHA FC (2 vs 2.5, p=0.005), especially if baseline NYHA FC>2 (2 vs 3, p=0.011). There was a noted decrease in cardiac hospitalization (4 vs 9) that did not reach statistical significance (p=0.313). Conclusions: ARNIs are associated with noticeable improvement in functional class without impact on objective measures in SRV patients. The study findings are promising and highlight the need for larger, prospective, multicenter studies.
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Rattanavipanon, Wipharak, Thanyaluck Sotananusak, Fairus Yamaae, Arisa Chandrsawang, Pitchapa Kaewkan, Surakit Nathisuwan, and Teerapat Yingchoncharoen. "Real-world experience of angiotensin receptor/neprilysin inhibitor (ARNI) usage in Thailand: a single-center, retrospective analysis." BMC Cardiovascular Disorders 21, no. 1 (July 2, 2021). http://dx.doi.org/10.1186/s12872-021-02145-9.
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Abstract 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.