Sacubitril and valsartan fixed combination to reduce heart failure
events in post-acute myocardial infarction patients

Iskandar, Zaid; Lang, Chim C.

doi:10.1358/dot.2017.53.10.2722396

Cited by 14 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Besides the benefits of LCZ696 in patients with systolic HF, the effects of LCZ696 in patients with MI are of more interest to clinicians. Another trial, the PARADISE-MI trial, has been ongoing to examine the effects of LCZ696 in patients with acute myocardial infarction (MI) and HF [5]. Results from the PARADISE-MI study are being expected by all cardiologists.…”

Section: Introductionmentioning

confidence: 99%

LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model

Chang

Lin

Chu

et al. 2019

Cardiovascular Therapeutics

View full text Add to dashboard Cite

Background. LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of NaV1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K+ channel proteins.

show abstract

Section: Introductionmentioning

confidence: 99%

LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model

Chang

Lin

Chu

et al. 2019

Cardiovascular Therapeutics

View full text Add to dashboard Cite

show abstract

“…However, this study follows the patients during only 8 weeks and data concerning hospitalization and cardiovascular mortality were still not available. New clinical trials addressing these questions are in course, such as PARADISE-MI 31 among others. Although the combination of ACEI and LCZ696 is not plausible, since it increases the risk of angioedema, as observed with Omapatrilat (combination of a neprilysin inhibitor with an ACEI), 36 we cannot rule out the association between LCZ696 and aliskiren, in spite of the fact that hypotension should be a concern.…”

Section: Discussionmentioning

confidence: 99%

“…Factors that may have influenced the results of these studies include the lower percentages of patients using beta-blockers (34.5%) and mineralocorticoid receptor antagonists (5%) in the Val-HeFT study (Table 1) than in the ASTRONAUT (81.7% and 55.4%, respectively) and ATMOSPHERE (92.0% and 36.6%, respectively) studies. 16,17,26,31 However, the effect of dual RAS blockade in reducing CV death and HF hospitalization cannot be attributed to sample size weighting differences in the aforementioned studies. The sample size weighting of the RD patient subgroup in the Val-HeFT 25 study (22.7%) was larger than those in the ASTRONAUT 17 (5.2%) and ATMOSPHERE 26 (13.8%) studies.…”

Section: Discussionmentioning

confidence: 99%

Effects of dual blockade in heart failure and renal dysfunction: Systematic review and meta-analysis

Silva

Martini

Canto

et al. 2019

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

Objective: The effect of dual renin–angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. Methods: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. Results: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 ( p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 ( p=0.0006) in all individuals, and to 0.86 ( p=0.005) in patients with RD and to 0.91 ( p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% ( p=0.00001). Conclusions: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.

show abstract

“…Na 186 pacientoch s infarktom myokardu s eleváciou ST-segmentu, včasné podanie sakubitril/valsartanu (vs. konvenčné ACEi) do 24 hodín po perkutánnej koronárnej intervencii redukovalo veľkosť infarktu meraného šesť mesiacov po príhode pomocou emisnej počítačovej tomografie (SPECT) (49). V súčasnosti prebieha multicentrická štúdia PARADISE-MI za účelom porovnania účinku sakubitril/ valsartanu a ramiprilu na kompozitný endpoint kardiovaskulárnej mortality, hospitalizácie pre SZ a ambulantného SZ u pacientov po prekonaní infarktu myokardu so systolickou dysfunkciou ĽK a štandardnou terapiou (50). Úspech tejto štúdie by mohol byť východiskovým bodom k využitiu sakubitril/valsartanu u pacientov so SZ následkom prekonaného infarktu myokardu.…”

Section: Infarkt Myokarduunclassified

Duálna inhibícia neprilyzínu a receptora typu 1 pre angiotenzín II vo svetle klinických štúdií / Dual inhibition of neprilysin and angiotensin II type 1 receptor in light of clinical studies

Mariani

Mattioli

Condorelli

et al. 2021

Cardiol

View full text Add to dashboard Cite

Despite advances in heart failure (HF) pharmacotherapy over the last three decades, the residual mortality with HF remains high. The antipode to the drug-induced inhibition of vasoconstrictive and proliferative substances could be an increase of vasodilative and antiproliferative humoral substances, including the natriuretic peptides (NPs). NPs are secreted by the distended myocardium and stimulate diuresis and vasodilation, exert antiproliferative effects, and inhibit both the sympathetic and renin-angiotensin systems (RAS). The proteolytic enzyme neprilysin cleaves NPs and thus limits their effects. However, this non-specific protease degrades a variety of other proteins, including angiotensin II (Ang II). Therefore, neprilysin inhibition increases the level of both NPs and Ang II. Sacubitril/valsartan, a representative of the new drug class: angiotensin receptor-neprilysin inhibitors (ARNi), contains one molecule of Ang II type 1 receptor blocker (valsartan) and one molecule of neprilysin inhibitor (sacubitril). The interaction of these substances, ensuing potential increase of NPs without RAS activation, brings an additive morbidity and mortality benefit in the management of HF with reduced ejection fraction (HFrEF), as compared to RAS inhibition alone. Yet, the hope for ARNi's benefit in HF with preserved ejection fraction (HFpEF) remains is unmet. Preliminary studies suggest a potential benefit by ARNi in hypertensive heart disease, kidney protection and post-myocardial infarction cardiac remodelling. Tab. 1, Ref. 50, on-line full text (Free, PDF) www.cardiologyletters.sk

show abstract

Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients

Cited by 14 publications

References 0 publications

LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model

LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model

Effects of dual blockade in heart failure and renal dysfunction: Systematic review and meta-analysis

Duálna inhibícia neprilyzínu a receptora typu 1 pre angiotenzín II vo svetle klinických štúdií / Dual inhibition of neprilysin and angiotensin II type 1 receptor in light of clinical studies

Contact Info

Product

Resources

About