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Entresto (sacubitril/valsartan)
Entresto (sacubitril/valsartan)
Related Topics:
News & Research:
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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"
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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"
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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.
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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"
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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"
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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"
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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"
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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"
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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.
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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"
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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"
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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"
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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!"
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