Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan) After Experimental Acute Myocardial Infarction

Ishii, Masanobu; Kaikita, Koichi; Sato, Koji; Sueta, Daisuke; Fujisue, Koichiro; Arima, Yuichiro; Oimatsu, Yu; Mitsuse, Tatsuro; Onoue, Yoshiro; Araki, Satoshi; Yamamuro, Megumi; Nakamura, Taishi; Izumiya, Yasuhiro; Yamamoto, Eiichiro; Kojima, Sunao; Kim‐Mitsuyama, Shokei; Ogawa, Hisao; Tsujita, Kenichi

doi:10.1016/j.jacbts.2017.08.001

Cited by 76 publications

(60 citation statements)

References 35 publications

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“…In experimental HFrEF models, it has been demonstrated that S/V improved cardiac function by reducing myocardial fibrosis, prevented cardiac rupture after myocardial infarction (MI) by inhibiting the inflammation and the degradation response of macrophages, and improved survival and LV volumes after MI if compared to enalapril 20 .…”

Section: Discussionmentioning

confidence: 99%

Clinical and echocardiographic benefit of Sacubitril/Valsartan in a real-world population with HF with reduced ejection fraction

Polito

Silverio

Rispoli

et al. 2020

Sci Rep

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The aim of this study was to evaluate the effects of Sacubitril/Valsartan (S/V) on clinical, laboratory and echocardiographic parameters and outcomes in a real-world population with heart failure with reduced ejection fraction (HFrEF). This was a prospective observational study enrolling patients with HFrEF undergoing treatment with S/V. The primary outcome was the composite of cardiac death and HF rehospitalization at 12 months follow-up; secondary outcomes were all-cause death, cardiac death and the occurrence of rehospitalization for worsening HF. The clinical outcome was compared with a retrospective cohort of 90 HFrEF patients treated with standard medical therapy. The study included 90 patients (66.1 ± 11.7 years) treated with S/V. The adjusted regression analysis showed a significantly lower risk for the primary outcome (HR:0.31; 95%CI, 0.11-0.83; p = 0.019) and for HF rehospitalization (HR:0.27; 95%CI, 0.08-0.94; p = 0.039) in S/V patients as compared to the control group. A significant improvement in NYHA class, left ventricular ejection fraction, left ventricular end systolic volume and systolic pulmonary arterial pressure was observed up to 6 months. S/V did not affect negatively renal function and was associated with a significantly lower dose of furosemide dose prescribed at 6-and 12-month follow-up. In this study, S/V reduced the risk of HF rehospitalization and cardiac death at 1 year in patients with HFrEF. S/V improved NYHA class, echocardiographic parameters and need of furosemide, and preserved renal function.Despite the improvements in clinical management and medical therapy of heart failure (HF), the outcome of patients with HF and reduced ejection fraction (HFrEF) remains poor 1 . If compared to the other HF entities, this category shows distinct demographic characteristics, comorbidities, response to therapy, and a substantially higher risk of mortality secondary to sudden cardiac death (SCD) and rehospitalization for worsening HF 2 . Many HFrEF patients are still undertreated and several drugs, such as beta-blockers and ACE inhibitors (ACEi), are under-dosed. This issue is also related to the incorrect risk evaluation by clinicians, who are likely to consider the absence or paucity of symptoms as an indicator of HF stability 3 . In fact, HFrEF is a progressive disorder that, despite the improvement of patient's clinical status achieved with conventional medications, may be associated with a high risk of adverse events at short and long-term follow-up 4 .Current European guidelines 5 recommend the use Sacubitril/Valsartan (S/V), an angiotensin receptorneprilysin inhibitor (ARNI), in replacement of the renin-angiotensin-aldosterone system (RAAS) inhibition in ambulatory HFrEF patients still symptomatic despite optimal medical therapy (OMT). This recommendation comes from a single randomized study named PARADIGM-HF trial 6 , which showed the superiority of S/V compared to Enalapril in reducing the incidence of cardiovascular death or hospitalizations for HF. Few studies have so far investigat...

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Section: Discussionmentioning

confidence: 99%

Clinical and echocardiographic benefit of Sacubitril/Valsartan in a real-world population with HF with reduced ejection fraction

Polito

Silverio

Rispoli

et al. 2020

Sci Rep

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“…A previous report has illustrated that Sac/Val more strongly suppresses proinflammatory cytokine expression and inflammatory cell infiltration than ACEI, contributing to improved cardiac outcomes [ 31 ]. Here, we observed that infiltration of heart inflammatory cells was obviously ameliorated by Sac/Val treatment after DB surgery.…”

Section: Discussionmentioning

confidence: 99%

Protection of Sacubitril/Valsartan against Pathological Cardiac Remodeling by Inhibiting the NLRP3 Inflammasome after Relief of Pressure Overload in Mice

Zhu

Wang

et al. 2020

Cardiovasc Drugs Ther

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Background/aims The persistent existence of pathological cardiac remodeling, resulting from aortic stenosis, is related to poor clinical prognosis after successful transcatheter aortic valve replacement (TAVR). Sacubitril/valsartan (Sac/Val), comprising an angiotensin receptor blocker and a neprilysin inhibitor, has been demonstrated to have a beneficial effect against pathological cardiac remodeling, including cardiac fibrosis and inflammation in heart failure. The aim of this study was to determine whether Sac/Val exerts a cardioprotective effect after pressure unloading in mice. Methods and results Male C57BL/6 J mice were subjected to debanding (DB) surgery after 8 weeks (wk) of aortic banding (AB). Cardiac function was assessed by echocardiography, which indicated a protective effect of Sac/Val after DB. After treatment with Sac/Val post DB, decreased heart weight and myocardial cell size were observed in mouse hearts. In addition, histological analysis, immunofluorescence, and western blot results showed that Sac/Val attenuated cardiac fibrosis and inflammation after DB. Finally, our data indicated that Sac/Val treatment could significantly suppress NF-κB signaling and NLRP3 inflammasome activation in mice after relief of pressure overload. Conclusion Sac/Val exerted its beneficial effects to prevent maladaptive cardiac fibrosis and dysfunction in mice following pressure unloading, which was at least partly due to the inhibition of NLRP3 inflammasome activation.

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“…The PCP- HF tool also provides a framework that may be useful to test the efficacy of specific anti-hypertensive therapies among individuals at-risk for HF. For example, sacubitril/valsartan therapy, may be a novel anti-hypertensive therapy to be considered in individuals at high risk of HF given evidence of improvement in cardiac mechanics in preclinical and clinical studies [ 48 , 49 ]. A randomized-controlled trial is currently underway to investigate sacubitril/valsartan in the primary prevention of HF among individuals with an elevated natriuretic peptide levels (with a similar strategy to STOP-HF) in the Personalized Prospective Comparison of ARni with ArB in Patients with Natriuretic Peptide eLEvation [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Systematic examination of a heart failure risk prediction tool: The pooled cohort equations to prevent heart failure

et al. 2020

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Identification of individuals at risk for heart failure is needed to deliver targeted preventive strategies and maximize net benefit of interventions. To examine the clinical utility of the recently published heart failure-specific risk prediction model, the Pooled Cohort Equations to Prevent Heart Failure, we sought to demonstrate the range of risk values associated with diverse risk factor combinations in White and Black men and women. We varied individual risk factors while holding the other risk factors constant at age-adjusted national mean values for risk factors in each race-sex and age group. We also examined multiple combinations of risk factor levels and examined the range of predicted 10-year heart failure risk using the Pooled Cohort Equations to Prevent Heart Failure risk tool. Ten-year predicted heart failure risk varied widely for each race-sex group across a range of ages and risk factor scenarios. For example, predicted 10-year heart failure risk in a hypothetical 40 year old varied from 0.1% to 9.7% in a White man, 0.5% to 12.3% in a Black man, <0.1% to 9.3% in a White woman, and 0.2% to 28.0% in a Black woman. Higher risk factor burden (e.g. diabetes and hypertension requiring treatment) consistently drove higher risk estimates in all race-sex groups and across all ages. Our analysis highlights the importance of a race and sex-specific multivariable risk prediction model for heart failure to personalize the clinician-patient discussion, inform future practice guidelines, and provide a framework for future risk-based prevention trials for heart failure.

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Cardioprotective Effects of LCZ696 (Sacubitril/Valsartan) After Experimental Acute Myocardial Infarction

Abstract: Visual Abstract

Cited by 76 publications

References 35 publications

Clinical and echocardiographic benefit of Sacubitril/Valsartan in a real-world population with HF with reduced ejection fraction

Clinical and echocardiographic benefit of Sacubitril/Valsartan in a real-world population with HF with reduced ejection fraction

Protection of Sacubitril/Valsartan against Pathological Cardiac Remodeling by Inhibiting the NLRP3 Inflammasome after Relief of Pressure Overload in Mice

Systematic examination of a heart failure risk prediction tool: The pooled cohort equations to prevent heart failure

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