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Home > Health Conditions > Hypertension > Entresto (sacubitril/valsartan)

Entresto (sacubitril/valsartan)

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  • Efficacy and Safety of Sacubitril/Valsartan Compared With ACEI/ARB on Health-Related Quality of Life in Heart Failure Patients: A Meta-Analysis - Ann Pharmacother 2022 Dec 8 - "Sacubitril/valsartan may have the potential to improve HRQoL in heart failure patients with reduced ejection fraction compared with ACEI/ARB. Hypotension is the most common adverse event with sacubitril/valsartan compared with ACEI/ARB. The results of this study may contribute to the rational use of sacubitril/valsartan"
  • Effect of add-on sacubitril/valsartan on the left ventricular hypertrophy of a patient with hypertension - J Int Med Res 2022 Nov - "We treated a man in his late 40s who had undergone a percutaneous coronary intervention and had hypertension that was refractory to multiple anti-hypertensive medications. We initiated sacubitril/valsartan 200 mg/day as an add-on therapy, and 3 months later, his blood pressure had decreased from 154/78 mmHg to 134/70 mmHg, in the absence of any drug-related adverse events. Furthermore, his left ventricular mass index had improved from 135 g/m2 to 112 g/m2. Thus, sacubitril/valsartan might ameliorate hypertrophy in patients with hypertension"
  • Network meta-analysis of sacubitril/valsartan for the treatment of essential hypertension - Clin Res Cardiol 2022 Nov 3 - "In hypertensive patients, 200 mg once daily of sacubitril/valsartan may exert a greater reduction in ambulatory blood pressure than 100 mg once daily and 200 mg once daily may not be inferior to 400 mg once daily. Moreover, it is not clear that sacubitril/valsartan lowers blood pressure more than an angiotensin receptor blocker"
  • Dose-Response to Sacubitril/Valsartan in Patients With Heart Failure and Reduced Ejection Fraction - J Am Coll Cardiol 2022 Oct 18 - "The average daily dose was 112 mg in Tertile 1 (low dose), 342 mg in Tertile 2 (moderate dose), and 379 mg in Tertile 3 (high dose). Similar changes in prognostic biomarkers were observed in all dose tertiles. Gains in Kansas City Cardiomyopathy Questionnaire-23 scores were comparable regardless of dose category. Consistent reverse cardiac remodeling in all dose categories occurred; the median absolute left ventricular EF improvement across HF dose groups was 9.3%, 8.7%, and 10.2%, for low, moderate, and high doses, respectively; similar improvements in left atrial and ventricular volumes and E/e' were also observed across dose categories"
  • Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy - Circulation 2022 Sep 9 - "Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure"
  • Sacubitril/Valsartan Shows Cognitive Safety in Heart Failure: PERSPECTIVE - Medscape, 8/26/22 - "Treatment of patients with chronic heart failure with sacubitril/valsartan (Entresto), a mainstay agent for people with this disorder, produced no hint of incremental adverse cognitive effects during 3 years of treatment in a prospective, controlled, multicenter study with nearly 600 patients, although some experts note that possible adverse cognitive effects of sacubitril were not an issue for many heart failure clinicians, even before the study ran" - Note: There was concern early on that theoretically, Entresto could lead to Alzheimer's.
  • Effect of Entresto on Clinical Symptoms, Ventricular Remodeling, Rehabilitation, and Hospitalization Rate in Patients with Both Acute Myocardial Infarction and Acute Heart Failure - Evid Based Complement Alternat Med 2022 Aug 16 - "Totally 120 patients with AMI complicated with AHF admitted to our hospital between January 2017 and August 2019 were enrolled and randomly assigned to an observation group (obs group) and a control group (con group) (each n = 60). The obs group was treated with Entresto, while the other with angiotensin-converting enzyme inhibitors (ACEI). After treatment, the efficacy on both groups was evaluate ... After treatment, the obs group showed notably higher efficacy than the con group (P < 0.05). Before treatment, the two groups were not greatly different in LVESd, LVEDd, LVEF, IVST, LVMI, NT-pro BNP, CRP, and TNF-α (all P > 0.05), while after treatment, these indexes of both groups were improved, but the improvement in the obs group was more notable (P < 0.05). Additionally, the hospitalization time, treatment expense, readmission rate one year after discharge, and incidence of adverse events in the obs group were notably lower"
  • Application of Angiotensin Receptor-Neprilysin Inhibitor in Chronic Kidney Disease Patients: Chinese Expert Consensus - Front Med (Lausanne) 2022 Jul 19 - "A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin-angiotensin-aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin-angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD"
  • The Efficacy and Safety of Sacubitril-Valsartan for the Treatment of Heart Failure in Adults: A Meta-Analysis - Ann Pharmacother 2022 Aug 2 - "Data of included studies prove the efficacy and safety of SV for curing heart conditions. Therefore, the present evidence shows that SV is effective in the treatment of heart failure, reducing hospitalization and cardiovascular mortality, and that the adverse effects are comparable or fewer than those associated with other drugs used for this indication"
  • Sacubitril-Valsartan Increases Ultrafiltration in Patients Undergoing Peritoneal Dialysis: A Short-Term Retrospective Self-Controlled Study - Front Med (Lausanne) 2022 Jun 3 - "There are few data about the effectiveness and safety of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan in end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). The present study was conducted to evaluate the association between sacubitril-valsartan treatment and peritoneal ultrafiltration (PUF) in PD patients ... After treated with sacubitril-valsartan, 30 patients (63.8%) had a significant increase of PUF [up to 150.4 (110.7, 232.1) ml per day], while the remaining 17 (36.2%) had a slight decrease. The overall increase of PUF was 66.4 (21.4, 123.2) ml/24 h within the 7 days after sacubitril-valsartan administration, which was significantly higher than those before (P = 0.004). Total output, BP, and body weight also significantly improved. No adverse drug reactions were observed"
  • Angiotensin receptor-neprilysin inhibitors for hypertension-hemodynamic effects and relevance to hypertensive heart disease - Hypertens Res 2022 May 2 - "The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to effectively reduce ambulatory 24-h blood pressure in patients with hypertension, and improvements in many aspects of hemodynamic function have also been reported ... Overall, angiotensin receptor-neprilysin inhibitors regulate blood pressure and pulse pressure via multiple mechanisms and provide cardiovascular protection. This provides an option for effective intervention early in the vicious cycle of elevated blood pressure and central pressures with progression toward heart failure that should help to address the growing worldwide heart failure epidemic"
  • The Effect of Sacubitril/Valsartan Treatment on Cardiac and Renal Functions of a Patient With Cardiorenal Syndrome Type 4 and Stage 5 CKD After More Than Three Years of Follow-Up - Front Med (Lausanne) 2022 Mar 11 - "In our hospital, she received sacubitril/valsartan treatment for at least 40 months. The symptoms of HF relieved, and the indices of cardiac function improved. In addition, the patient's renal function was stable. During the treatment, the dosage of sacubitril/valsartan needed to be adjusted to achieve the optimal therapeutic effect. Follow-up results showed that she achieved cardiac function of New York Heart Association (NYHA) class II with an ejection fraction of 0.60 and E/A > 1 indicated by echocardiogram, and did not develop hyperkalemia. In summary, the improvement of cardiac and renal functions of the CRS4 patient was associated with the long-term sacubitril/valsartan treatment"
  • Heart Failure With Preserved Ejection Fraction: New Treatments Provide 'Hope' - Medscape, 3/28/22 - "That is, those individuals in PARAGON-HF who had ejection fractions slightly on the lower end of "normal" tended to benefit more from this medication as well. That differentiated by sex. This is a controversial aspect of the field and it is something that's evolving on a day-to-day or month-to-month basis ... Sacubitril-valsartan, I think, would be a medicine that could be of particular benefit in this patient. That was the first of the next few trials in HFpEF that started to yield potential new drug classes for HFpEF. ... The next drug class is one with which all aspects of cardiology have become more and more aware, and the HFpEF field is no stranger. With the results of the EMPEROR-Preserved trial we have, in the history of HFpEF clinical trials, our first positive trial, and a monumental moment. A trial evaluating the efficacy of empagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) vs placebo in HFpEF. This is the ideal patient who may benefit from this medicine ... EMPEROR-Preserved demonstrated a reduction in a composite endpoint of heart failure hospitalization and cardiovascular death. As you mentioned, Clyde, this efficacy was driven by a reduction in heart failure hospitalization. The class of SGLT2 inhibitors would be, certainly, a medicine that would provide much benefit not only from a reduction in heart failure hospitalization perspective, but a marked improvement in symptoms" - See empagliflozin at ihouseepharmacy.
  • A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction - Medscape, 3/21/22 - "In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i"
  • Efficacy of sacubitril/valsartan versus olmesartan in Japanese patients with essential hypertension: a randomized, double-blind, multicenter study - Hypertens Res 2022 Jan 21 - "Patients (n = 1161, aged ≥20 years) with mild to moderate hypertension (mean sitting systolic blood pressure [msSBP] ≥150 to <180 mmHg) were randomized to receive sacubitril/valsartan 200 mg (n = 387), sacubitril/valsartan 400 mg (n = 385), or olmesartan 20 mg (n = 389) once daily for 8 weeks. The primary assessment was a reduction in msSBP from baseline with sacubitril/valsartan 200 mg vs. olmesartan 20 mg at Week 8. Secondary assessments included msSBP reduction with sacubitril/valsartan 400 mg vs. olmesartan at Week 8 and reductions in mean sitting diastolic blood pressure (msDBP), mean sitting pulse pressure (msPP), and overall blood pressure (BP) control rate for all treatment groups at Week 8. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP from baseline than olmesartan at Week 8 (between-treatment difference: -5.01 mmHg [95% confidence interval: -6.95 to -3.06 mmHg, P < 0.001 for noninferiority and superiority]). Greater reductions in msSBP with sacubitril/valsartan 400 mg vs. olmesartan, as well as in msDBP and msPP with both doses of sacubitril/valsartan vs. olmesartan (P < 0.05 for all), were also observed. Patients treated with sacubitril/valsartan achieved an overall higher BP control rate. The safety and tolerability profiles of sacubitril/valsartan were generally comparable to those of olmesartan. The adverse event rate with sacubitril/valsartan was not dose-dependent. Treatment with sacubitril/valsartan was effective and provided superior BP reduction, with a higher proportion of patients achieving target BP goals than treatment with olmesartan in Japanese patients with mild to moderate essential hypertension"
  • Time to switch angiotensin-converting enzyme inhibitors/angiotensin receptor blockers to sacubitril/valsartan in patients with cancer therapy-related cardiac dysfunction - J Int Med Res 2022 Jan - "Advances in cancer therapy have resulted in more cancer therapy-related cardiac dysfunction (CTRCD), which is the main cause of death in older female survivors of breast cancer. Traditionally, guideline-recommended medications for heart failure, such as beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), are commonly used to prevent or attenuate CTRCD. However, sometimes their effectiveness is not satisfactory. Recently, the drug combination of sacubitril plus valsartan has been proven to be more beneficial for heart failure with reduced ejection fraction in the long term compared with an ACEI/ARB alone. However, there is a lack of evidence of the efficacy and safety of this drug combination in CTRCD. We report a case of worsening CTRCD, despite treatment with traditional medications, in which the patient improved after changing perindopril to sacubitril/valsartan. The patient's heart function greatly improved after changing this ACEI to sacubitril/valsartan. Changing an ACEI/ARB to sacubitril/valsartan in patients with worsening chemotherapy-induced heart failure is appropriate"
  • Sacubitril/Valsartan May Alter Trajectory of Preclinical HFpEF - Medscape, 11/23/21 - "Sacubitril/valsartan (Entresto) appears to improve measures of cardiac structure and function compared with valsartan alone in asymptomatic preclinical heart failure with preserved ejection fraction ... Sacubitril/valsartan (Entresto) appears to improve measures of cardiac structure and function compared with valsartan alone in asymptomatic preclinical heart failure with preserved ejection fraction ... Preclinical heart failure with preserved ejection fraction (HFpEF), the dominant form of preclinical HF, is largely driven by CV compliance abnormalities. Sacubitril/valsartan, through preservation of natriuretic peptide (NP), may improve CV compliance, especially if introduced early in the disease process ... At baseline, the left atrial volume index (LAVI) was 33.2 mL/m2 using Doppler echocardiography and 50 mL/m2 using cardiac MRI. "The discrepancy you see with cardiac MRI is a notable feature in the literature, but maybe something that's not as widely appreciated as it should be," ... The primary outcome of change in maximal LAVI over 18 months by cardiac MRI was 6.9 mL/m2 with sacubitril/valsartan vs 0.7 mL/m2 with valsartan alone ... Sacubitril/valsartan was also associated with a significant change in left ventricular end-diastolic volume index (7.1 mL/m2 vs 1.4% mL/m2 ... Over a median 16.9 months of follow-up, sacubitril/valsartan reduced 24-hour pulse pressures by -4.2 mm Hg vs -1.2 mm Hg with valsartan alone ... Following the presentation, an audience member asked whether the results may endorse the use of sacubitril/valsartan as an antihypertensive — an indication already approved in some countries ... "That's a fascinating question," McDonald replied. "When you look at the mechanisms of action of this agent compared to other antihypertensive agents and, particularly its beneficial effect of vasoprotective peptides, there's good reason to suspect it may be of more benefit than standard therapies, especially in those people who've shown at risk for the development of cardiovascular events.""
  • Expanded Label for Sacubitril/Valsartan Makes 1.8 Million More HF Patients Eligible - Medscape, 9/28/21 - "The expanded indication was based on results of the PARAGON-HF trial. While the trial missed its primary endpoint, secondary subgroup analyses showed a significant interaction between LVEF and treatment efficacy, with patients with a mid-range (below-median) LVEF of 45% to 57% appearing to benefit from sacubitril/valsartan therapy"
  • Outcome Benefits Seen With 1 Year of Optimized Sacubitril/Valsartan for the Treatment of Systolic Heart Failure Managed by Pharmacists in a Cardiology Practice - Ann Pharmacother 2021 Aug 28 - "patients with HF with reduced ejection fraction (HFrEF) on angiotensin receptor-neprilysin inhibitor (ARNi) therapy optimized within a pharmacist clinic ... Retrospective chart review of patients with HFrEF on sacubitril/valsartan ... For the primary outcome analysis, 70 patients with pre/post hospitalization data had a reduction in the rate of all-cause hospitalization from 45.7% in the 12 months prior to ARNi therapy initiation to 24.3% during the first year on optimized ARNi therapy (P = 0.004). The rate of hHF reduced from 24.3% to 8.6% (P = 0.003). For the secondary outcome analyses at the 6-month assessment point, which included 104 patients, ejection fraction improved from 26% to 34% (P < 0.001), NYHA FC improved or remained unchanged in 86.6% of patients, and weekly loop diuretic dosing requirements were significantly reduced"
  • Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction - Eur Heart J 2021 Aug 15 - "Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on 'apparent resistant hypertension' in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril-valsartan with valsartan ... Sacubitril-valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA"
  • Sacubitril/valsartan for heart failure with preserved ejection fraction and resistant hypertension: one shot for a double strike? - European Heart Journal, 8/15/21 - "hypertension and HFpEF co-exist in >95% of subjects,5 and a large proportion of HFpEF patients have uncontrolled blood pressure (BP) levels despite the use of multiple antihypertensive drugs. Indeed, resistant hypertension, defined as the failure to achieve recommended BP targets despite appropriate lifestyle measures and treatment with optimal or best-tolerated doses of three or more drugs which should include a diuretic [typically an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) and a calcium channel blocker (CCB)]1,6, accounts for 10–20% of HFpEF patients ... Sac/Val appeared to be more effective than valsartan alone in treating resistant hypertension in HFpEF. Patients treated with Sac/Val achieved a 4.8 mmHg SBP reduction (–7.0 to –2.5 mmHg) compared with –3.9 mmHg (–6.6 to –1.3 mmHg) in the valsartan group. Consistent results were obtained in individuals with apparent MRA-resistant hypertension [–8.8 mmHg (–14.0 to –3.5 mmHg) vs. –6.3 (–12.5 to –0.1 mmHg) in the Sac/Val and valsartan groups, respectively]. Sac/Val improved the achievement of SBP control at 16 weeks by 22% compared with valsartan alone [47.9% vs. 34.3%; adjusted odds ratio (OR) 1.78; 95% CI 1.30–2.43]. In patients with apparent MRA-resistant hypertension, the proportions were 43.6% vs. 28.4%, respectively, with an adjusted OR of 2.63"
  • Effectiveness of Sacubitril/Valsartan Versus Aldosterone Antagonists in Heart Failure with reduced Ejection Fraction: A Retrospective Cohort Study - Pharmacotherapy 2021 Jun 25 - "aldosterone antagonists (ARAs) ... Compared with ARAs, SAC/VAL was associated with lower risk of HF-related and all-cause hospitalizations"
  • Sacubitril/Valsartan: Trending Toward PARADISE Post MI? - Medscape, 5/19/21 - See the graph.  The thing is, ramipril has has an annoying side effect (a hacking cough).  Also notice how Entresto and ramipril compare to the ARB valsartan.

  • PARADISE-MI: Sacubitril/Valsartan Can't Beat Ramipril in Patients With Acute MI - Medscape, 5/15/21 - "Treatment with sacubitril/valsartan, a pillar of therapy for patients with chronic heart failure with below-normal ejection fraction, came suggestively close to showing efficacy for preventing cardiovascular death or heart failure events in patients who have just had an MI but have no history of heart failure in a controlled trial with more than 5,600 patients ... Although sacubitril/valsartan (Entresto) fell short of producing a significant benefit, it did show good safety that was similar to the study's comparator treatment, ramipril, an agent from the angiotensin-converting enzyme inhibitor class that is a mainstay of treatment in these patients ... To say that, with no run-in, sacubitril/valsartan is as well tolerated and as safe as one of the best-studied ACE inhibitors – ramipril – in acutely ill MI patients, is a big statement ... This high level of safety without gradual uptitration of sacubitril/valsartan (Entresto) "should lower barriers" to broader use of the dual-drug formulation for its approved indication in patients with chronic heart failure, especially patients with a left ventricular ejection fraction that is below normal. In addition, results from the PARADISE-MI trial suggested that "patients seemed to benefit before they develop heart failure. We couldn't prove that, but we should build on this, and make it easier for patients to use this treatment," Dr. Pfeffer said during a press briefing following his talk at the sessions"
  • Effects of Sacubitril/Valsartan on clinical symptoms, echocardiographic parameters, and outcomes in HFrEF and HFmrEF patients with coronary heart disease and chronic kidney disease - Curr Med Res Opin 2021 Mar 25 - "To compare the effects of Angiotensin Receptor-Neprilysin inhibitor (ARNI) on the clinical symptoms, echocardiographic parameters, and outcomes (cardiovascular death and hospitalization) in heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF) patients with coronary heart disease and chronic kidney disease ... A statistically significant increase of 68.8% was observed in left ventricular ejection fraction (LVEF) in HFrEF patients compared to that in HFmrEF patients, with an increase of 27.2% at 8 months of follow-up. Sacubitril/valsartan significantly reduced left ventricular end-systolic volumes (LVESV) in HFrEF patients unlike in HFmrEF patients. The decrease in LVESV was 28.8% in HFrEF patients and 17.1% in HFmrEF patients. A significant reduction in the prevalence of severe secondary mitral regurgitation (EROA >0.4cm2) was observed in HFrEF compared to that in HFmrEF patients with the use of sacubitril/valsartan. A reduction of 15.6% was observed in HFrEF patients, whereas a reduction of 7.1% was observed in HFmrEF patients. Improvement in functional classification (NYHA) was observed during follow-up. The prevalence of (NYHA III) reduced from 50% to 15.7% in HFrEF patients, whereas a reduction from 21.1% to 8.8% was observed in HFmrEF patients. There was a significant reduction in NT-proBNP in HFrEF patients compared to that in HFmrEF patients. A reduction of 52% was observed in HFrEF patients, whereas a reduction of 28.7% was observed in HFmrEF pateints. Sacubitril/valsartan reduced primary endpoint events in both groups. The prevalence of HF-related hospitalization was higher in HFrEF than in HFmrEF patients: 12.1% vs 7.5%, respectively. The prevalence of CV death in HFrEF vs HFmrEF patients was 3.7% vs 0.5%, respectively. Cardiovascular (CV) was higher in patients with atrial fibrillation in both groups"
  • FDA Expands Sacubitril/Valsartan Indication to Embrace Some HFpEF - Medscape, 2/17/21 - "The US Food and Drug Administration (FDA) has approved a groundbreaking expanded indication for sacubitril/valsartan (Entresto), making it the first drug in the United States indicated for chronic heart failure (HF) not specifically characterized by ejection fraction ... PARAGON-HF had assigned more than 4800 patients whose LVEF was 45% or higher and were in NYHA class 2-4 to receive sacubitril/valsartan or valsartan only. Those taking the combo drug showed a 13% drop in risk for HF hospitalization or cardiovascular deaths over an average of 3 years, which narrowly missed significance (P = .059) ... But a subgroup analysis garnered attention for its hint of benefit for patients with "mid-range" LVEF, in this case, below the median of 57%. The finding was supported by a later PARAGON-HF and PARADIGM-HF meta-analysis that pointed to a significant benefit for patients with HFpEF at its lowest LVEF levels, especially in women"
  • Five Reasons Sacubitril/Valsartan Should NOT Be Approved for HFpEF - Medscape, 1/15/21
  • FDA Panel Supports Expanded HF Role for Sacubitril/Valsartan - Medscape, 12/15/20 - "The U.S. Food and Drug Administration asked its Cardiovascular and Renal Drugs Advisory Committee to broadly consider whether new analyses of data from the PARAGON-HF trial, combined with other information, could support use of sacubitril/valsartan (Entresto, Novartis) in heart failure with preserved ejection fraction (HFpEF) ... The advisory committee voted 12-1 on this question"
  • Sacubitril/Valsartan: Neprilysin Inhibition 5 Years After PARADIGM-HF - Medscape, 12/4/20 - "Sacubitril/valsartan is an efficacious, safe, and cost-effective therapy that improves quality of life and longevity in patients with chronic HFrEF and reduces hospital admission. An in-hospital initiation strategy offers a potentially new avenue to improve the clinical uptake of sacubitril/valsartan ... The recently completed PARAGON-HF trial showed that sacubitril/valsartan modestly reduced the risks of total heart failure hospitalizations and cardiovascular death than valsartan in patients with HFpEF, although this finding narrowly missed statistical significance,[18] Clinical benefits were observed in secondary endpoints including quality of life and kidney endpoints; women and patients at the lower end of the LVEF spectrum appeared to preferentially benefit. The safety profile of sacubitril/valsartan was largely consistent with prior trial experiences. Regulatory review of sacubitril/valsartan for the treatment of HFpEF is currently under way. Ongoing trials are evaluating the clinical utility of sacubitril/valsartan among patients with HFpEF (PARALLAX) and acute myocardial infarction ... In the last 5 years, sacubitril/valsartan has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF. The next 5 years should see its wider implementation in practice and potential expansion of its therapeutic indications"
  • Entresto Halves Renal Events in Preserved EF Heart Failure Patients - Medscape, 10/14/20 - "sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint — renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) ... Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function"
  • EMPEROR-Reduced: Empagliflozin's HFrEF Benefit Holds Steady on Top of Sacubitril/Valsartan - Medscape, 10/7/20 - "When there are two very effective treatments, it's common for people to ask: Which should I use?' The goal of my presentation was to emphasize that the answer is both. We shouldn't choose between neprilysin inhibition [sacubitril inhibits the enzyme neprilysin] and SGLT2 [sodium-glucose transporter 2] inhibition; we should use both"
  • In-hospital Start of Sacubitril-Valsartan - Medscape, 8/17/20 - "From a healthcare system perspective, initiation of sacubitril-valsartan during hospitalization saved $452 per year compared with continuing enalapril (Vasotec), and $811 per year compared with initiation at 2 months after hospitalization ...Compared with continuation of enalapril indefinitely, switching patients to sacubitril-valsartan during their HF admission was associated with a cost per quality-adjusted life-year (QALY) gained of $21,532 ... As modeled in this study, starting the drug during hospitalization was associated with 62 fewer HF-related admissions per 1000 patients compared with outpatient initiation at 2 months (similar to the PARADIGM-HF strategy) and 116 fewer HF-related admissions compared with continuation of enalapril treatment ... the researchers also saw a reduction in HF-related readmissions with sacubitril-valsartan compared with enalapril. Rehospitalization for HF, which was assessed as part of a composite clinical events endpoint, was reduced from 13.8% in the enalapril arm to 8% with sacubitril-valsartan"
  • Ejection Fraction in Heart Failure Revisited-Where Does the Evidence Start? - Medscape, 7/27/20 - "The authors observed a similar effect on treatment with sacubitril/valsartan as in placebo-controlled trials in the low EF group. Interestingly, at an EF of from 40% to <55%, a clear sign for risk reduction was also observed"
  • SAVE-ICD: For Some, Sacubitril/Valsartan May Obviate Need for ICD - Medscape, 7/3/20 - "After 6 months of therapy with the combination drug sacubitril/valsartan (S/V; Entresto, Novartis), one quarter of primary prevention patients with left heart failure and an implantable cardioverter defibrillator (ICD) had a left ventricular ejection fraction (LVEF) > 35% with no arrhythmic events"
  • HFpEF: Gender Difference in Sacubitril/Valsartan Response Remains Mystery - Medscape, 4/20/20 - "In women, however, who comprised more than half of the study population, the benefit of sacubitril/valsartan was larger: a 27% relative risk reduction compared to valsartan alone. That's a statistically significant difference in a prespecified subgroup analysis, but according to the rules of clinical trials and statistics it must be considered hypothesis-generating and nondefinitive, since the overall trial was negative. Men randomized to sacubitril/valsartan had a modest 3% increased risk of the primary endpoint compared to men on valsartan."
  • Tolerability and efficacy of Sacubitril/ Valsartan in clinical practice - Intern Med J. 2020 Jan 6 - "Heart failure is a major cause of morbidity and mortality. Sacubitril/Valsartan has demonstrated reductions in HF hospitalisation, and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) ... 14% of patients were able to able to achieve maximal dose (97/103 mg twice daily) whilst 37% remained on 49/51 mg and 23% on 24/26 mg. The mean SBP reduced from 118 ± 18 mmHg to 109 ± 15 mmHg with symptomatic hypotension (30%) being the most common side effect leading to dose reduction or drug cessation. Left ventricular ejection fraction (LVEF) improved from 29.1 ± 9.7% to 33.8 ± 9.9% (p < 0.05) on drug. There was also a significant improvement in quality of life scores; EQ5D-VAS 40 pre vs 67 post Sacubitril/Valsartan (p < 0.05), and New York Heart Association class (p < 0.05). Importantly, ten patients lost an existing indication for device based therapy after treatment with Sacubitril/Valsartan ... Sacubitril/Valsartan is a much needed therapeutic advancement in the treatment of HF. Our study indicates it is well tolerated with improvements in cardiac function and symptoms. Sacubitril/Valsartan could redefine the definition of "optimal medical therapy' when assessing patients for device based therapies"
  • Sacubitril/Valsartan Benefits Extend to HF With Mildly Reduced EF - Medscape, 11/17/19 - "Further analyses of the PARADIGM and PARAGON heart failure trials of sacubitril/valsartan (Entresto, Novartis) appear to show that the benefits of the drug combination established in patients with low ejection fraction (EF) appear to extend to patients with mildly reduced EF, and to a higher EF range in women than men ... When the results were examined according to baseline EF, women showed a benefit of sacubitril/valsartan across the range of EFs up to about 65%. But in men, the benefit was attenuated at around 55%"
  • Entresto Sales See Slow and Steady Upturn - Medscape, 10/25/19 - "Despite narrowly missing its primary end point of heart failure (HF) hospitalization or cardiac deaths among patients with HF and preserved ejection fraction in PARAGON-HF, subgroup analyses in patients with an ejection fraction up to 57% and women showed significant benefits"
  • PROVE-HF Cracks the 'Holy Grail' of Cardiac Remodeling in HFrEF - Medscape, 10/7/19 - 14 minute video on Entresto to improve for low ejection fraction. - "For the group as a whole, by 6 months we saw an average 5.2% increase in the EF, and by 1 year a 9.5% rise in the EF."
  • Is Sacubitril/Valsartan (Also) an Antiarrhythmic Drug? - Medscape, 10/8/18 - "No randomized ICD trials have been performed yet in patients receiving sacubitril/valsartan, but it is reasonable to assume that, as new therapies improve overall survival and reduce sudden death, the additional survival benefit provided by an ICD will become narrower. In this new era of HF management, we may need to reassess the role of ICDs in primary prevention for patients with HF in the context of angiotensin receptor neprilysin inhibitor therapy added to β-blockers and mineralocorticoid receptor antagonists, especially if evidence continues to suggest antiarrhythmic effects of sacubitril/valsartan"
  • Shock and Awe: Sacubitril/Valsartan for Severe HF Safely Started in ICU in Early Cases - Medscape, 9/17/19 - "When they left the ICU, on average they had a significant improvement"
  • Sex, Intimacy Improved on Sacubitril/Valsartan in Heart Failure - Medscape, 4/10/18 - "Improvements over 36 months were most pronounced in domains that reflected being able to work, do household chores or recreational activities, climb stairs, and have intimate and sexual relationships ... It's kind of saying these patients are feeling as if they are 9 years younger"
    • 10 Things to Know About New Heart Failure Med Entresto - goodrx.com - "Sacubitril is the newer half of Entresto. Bear with me for some details. Inhibiting neprilysin raises levels of several peptides (small proteins) that have beneficial effects on blood flow in patients with HF. Remember that low cardiac output (low blood flow because the heart can’t squeeze well) is the main problem in heart failure. Saccubitril, the neprilysin inhibitor in Entresto, improves blood flow to the kidneys and improves removal of fluid (diuresis), among other things."
    • Entresto: Are You Ready To Trade Heart Failure For Alzheimer’s? - The Daily Health, 11/16/16 - "One of the key ingredients in Entresto – known as sacubitril – prevents the enzyme that breaks down amyloid beta plaques from doing its job. If these amyloid beta plaques are not broken down properly they can accumulate in our brains and can cause dementia and Alzheimer’s ... So while Entresto promises to be a silver bullet for your heart, it could also be a bullet through your brain!"