Sacubitril/valsartan in patients with symptomatic chronic heart failure with reduced ejection fraction

Background: Sacubitril/valsartan is a combination drug therapy for heart failure (HF) patients that has been shown to reduce mortality and hospitalisation. Aims: To explore clinically relevant real-life patient data regarding prescribing of sacubitril/valsartan for HF patients in three hospitals, in accordance with national guidelines. Methods: A retrospective multicentre study in three large UK hospital Trusts based in the West Midlands. Findings: A total of 118 symptomatic chronic HF patients with reduced ejection fraction were included in the study. A high proportion of prescribers adhered to NICE guidelines for treatment with sacubitril/valsartan; 99% of patients had a New York Heart Association functional class of at least II; 82% had a left ventricle ejection fraction of under 35%; 100% received an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker before commencing sacubitril/valsartan. The mean age of men and women at the three hospitals was 65 and 59 years, respectively. The proportion of men prescribed sacubitril/valsartan was greater than women: 80% compared to 20%, respectively. The majority of patients on the therapy were white British (65%). Total prescribing of sacubitril/valsartan at the three hospitals was 295 patients, lower than expected. Conclusion: The prescribing of sacubitril/valsartan at the Trusts generally adhered to NICE guidance; however, the prescribing rate was lower than expected compared with the NICE resource tool. Further investigations into the safety and scope of application of sacubitril/valsartan are required to match the prescribing of sacubitril/valsartan with eligible patients who could benefit from the medication.

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Sacubitril/Valsartan (Entresto®)-Induced Hyponatremia

Journal of Pharmacy Practice ◽

10.1177/0897190019828915 ◽

2019 ◽

Vol 33 (5) ◽

pp. 696-699 ◽

Cited By ~ 2

Author(s):

Ilana Fuzaylova ◽

Chester Lam ◽

Om Talreja ◽

Amgad N. Makaryus ◽

Deborah Ahern ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Elderly Woman ◽

Angiotensin Ii Receptor Blocker ◽

Angiotensin Receptor ◽

Angiotensin Ii Receptor ◽

Combination Drug ◽

Reduced Ejection Fraction ◽

Neprilysin Inhibitor ◽

Angiotensin Receptor Neprilysin Inhibitor

Sacubitril/valsartan (Entresto®) is the first commercially available angiotensin receptor neprilysin inhibitor (ARNI) approved for use in heart failure patients with a reduced ejection fraction. It is a combination drug that contains sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker. Our report outlines a case of probable ARNI-induced hyponatremia occurring in an elderly woman with heart failure with a reduced ejection fraction. According to Naranjo Adverse Drug Reaction Assessment, score indicated a likely association between patient’s hyponatremia and her use of sacubitril/valsartan.

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Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.733475 ◽

2021 ◽

Vol 12 ◽

Author(s):

Giuseppe Armentaro ◽

Graziella D’Arrigo ◽

Marcello Magurno ◽

Alfredo F. Toscani ◽

Valentino Condoleo ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Real Life ◽

Functional Class ◽

Left Ventricular Ejection ◽

Reduced Ejection Fraction ◽

Repeated Observations ◽

Nyha Functional Class ◽

Echocardiographic Parameters

Heart failure (HF) represents a widespread health problem characterized by high morbidity and mortality. Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by HF with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effectiveness and durability of sac/val treatment on the clinical, hemodynamic and echocardiographic parameters, in real-life consecutive HFrEF outpatients, evaluated up to 2-years of follow-up. We collected 300 repeated observations over time in 60 patients suffering of HFrEF and symptomatic despite optimal drug therapy. Patients with left ventricular ejection fraction (LVEF) <35 and II-III NYHA functional class were considered. All patients underwent to clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 24 months to evaluate possible clinical benefits and adverse events. During a 2-year follow-up period and through a 6-monthly control of the study variables both clinical, hemodynamic, biochemical and echocardiographic parameters significantly improved, in particular cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS). Furthermore, there was a reduction of NT-proBNP levels and betterment of renal function and NYHA functional class, demonstrating the efficacy and durability of sac/val treatment. In a multiple linear mixed model the longitudinal evolutions of CI were associated to concomitant changes of GLS and E/e’ ratio. Our study, contemplating the collection of 300 repeated observations in 60 patients, provides a complete and detailed demonstration of sac/val effects, showing effectiveness, safety and effect durability of the treatment every 6 months up to 2-years of follow-up with significant improvement of several clinical, hemodynamic and echocardiographic parameters in HFrEF outpatients.

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Use of Free-Living Step Count Monitoring for Heart Failure Functional Classification: Validation Study (Preprint)

10.2196/preprints.12122 ◽

2018 ◽

Author(s):

Jonathan-F. Baril ◽

Simon Bromberg ◽

Yasbanoo Moayedi ◽

Babak Taati ◽

Cedric Manlhiot ◽

...

Keyword(s):

Heart Failure ◽

Pilot Study ◽

Ejection Fraction ◽

Functional Class ◽

Step Count ◽

Functional Classification ◽

Free Living ◽

Reduced Ejection Fraction ◽

Nyha Functional Class ◽

Daily Total

BACKGROUND The New York Heart Association (NYHA) functional classification system has poor inter-rater reproducibility. A previously published pilot study showed a statistically significant difference between the daily step counts of heart failure (with reduced ejection fraction) patients classified as NYHA functional class II and III as measured by wrist-worn activity monitors. However, the study’s small sample size severely limits scientific confidence in the generalizability of this finding to a larger heart failure (HF) population. OBJECTIVE This study aimed to validate the pilot study on a larger sample of patients with HF with reduced ejection fraction (HFrEF) and attempt to characterize the step count distribution to gain insight into a more objective method of assessing NYHA functional class. METHODS We repeated the analysis performed during the pilot study on an independently recorded dataset comprising a total of 50 patients with HFrEF (35 NYHA II and 15 NYHA III) patients. Participants were monitored for step count with a Fitbit Flex for a period of 2 weeks in a free-living environment. RESULTS Comparing group medians, patients exhibiting NYHA class III symptoms had significantly lower recorded 2-week mean daily total step count (3541 vs 5729 [steps], P=.04), lower 2-week maximum daily total step count (10,792 vs 5904 [steps], P=.03), lower 2-week recorded mean daily mean step count (4.0 vs 2.5 [steps/minute], P=.04,), and lower 2-week mean and 2-week maximum daily per minute step count maximums (88.1 vs 96.1 and 111.0 vs 123.0 [steps/minute]; P=.02 and .004, respectively). CONCLUSIONS Patients with NYHA II and III symptoms differed significantly by various aggregate measures of free-living step count including the (1) mean and (2) maximum daily total step count as well as by the (3) mean of daily mean step count and by the (4) mean and (5) maximum of the daily per minute step count maximum. These findings affirm that the degree of exercise intolerance of NYHA II and III patients as a group is quantifiable in a replicable manner. This is a novel and promising finding that suggests the existence of a possible, completely objective measure of assessing HF functional class, something which would be a great boon in the continuing quest to improve patient outcomes for this burdensome and costly disease.

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Renal effects of Sacubitril/Valsartan in heart failure with reduced ejection fraction: a real life 1-year follow-up study

Internal and Emergency Medicine ◽

10.1007/s11739-019-02111-6 ◽

2019 ◽

Vol 14 (8) ◽

pp. 1287-1297 ◽

Cited By ~ 14

Author(s):

Francesco Spannella ◽

Marco Marini ◽

Federico Giulietti ◽

Giulia Rosettani ◽

Matteo Francioni ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Real Life ◽

Renal Effects ◽

Reduced Ejection Fraction ◽

Follow Up Study

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Effect of Empagliflozin on the Clinical Stability of Patients with Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial

Circulation ◽

10.1161/circulationaha.120.051783 ◽

2020 ◽

Cited By ~ 2

Author(s):

Milton Packer ◽

Stefan D. Anker ◽

Javed Butler ◽

Gerasimos S. Filippatos ◽

João Pedro Ferreira ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Functional Class ◽

Hazard Ratio ◽

Double Blind ◽

Reduced Ejection Fraction ◽

Risk Of Death ◽

Nyha Functional Class ◽

Patients With Heart Failure

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure. Methods: We randomly assigned 3730 patients with class II-IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite endpoints. Results: Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 vs 519 patients; empagliflozin vs placebo, respectively; hazard ratio 0.76, 95% CI: 0.67-0.87), P <0.0001. This benefit reached statistical significance at 12 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio 0.67, 95% CI 0.50-0.90, P=0.008) and that required a vasopressor or positive inotropic drug or mechanical or surgical intervention (hazard ratio 0.64, 95% CI: 0.47-0.87, P=0.005). As compared with placebo, fewer patients in the empagliflozin group reported intensification of diuretics (297 vs 414), hazard ratio 0.67, 95% CI: 0.56-0.78, P<0.0001. Additionally, patients assigned to empagliflozin were 20-40% more likely to experience an improvement in NYHA functional class and were 20-40% less likely to experience worsening of NYHA functional class, with statistically significant effects that were apparent 28 days after randomization and maintained during long-term follow-up. The risk of any inpatient or outpatient worsening heart failure event in the placebo group was high (48.1 per 100 patient-years of follow-up), and it was reduced by empagliflozin (hazard ratio 0.70, 95% CI: 0.63-0.78), P<0.0001. Conclusions: In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03057977

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P974 Sacubitril/valsartan is well tolerated in patients with heart failure and a history of cancer

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.1197 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

M K Frey ◽

E Han ◽

H Arfsten ◽

N Pavo ◽

M Huelsmann ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cancer Patients ◽

Functional Class ◽

Reduced Ejection Fraction ◽

Non Hodgkin Lymphoma ◽

Patients With Heart Failure ◽

History Of ◽

History Of Cancer

Abstract Introduction Sacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalisations due to heart failure in patients with reduced ejection fraction when compared to enalapril. Until now, sacubitril/valsartan has not been evaluated in patients with a history of cancer, as these patients were excluded from the pivotal trial, PARADIGM-HF. The aim of the current study was to assess tolerability of sacubitril/valsartan in patients with a history of cancer. Methods We retrospectively enrolled all patients at our heart failure out-patient unit who fulfilled the indication criteria to receive sacubitril/valsartan and had a history of cancer. Fifteen patients receiving sacubitril/valsartan had a diagnosis of histologically confirmed cancer: 26.7% breast cancer (n = 4), 13.3% osteosarcoma (n = 2), 13.3% colorectal cancer (n = 2), 13.3% renal cell carcinoma (n = 2), 6.7% non-Hodgkin lymphoma (n = 1), 6.7% lung cancer (n = 1), 6.7% prostate cancer (n = 1), 6.7% bladder carcinoma and 6.7% myeoloproliferative syndrome (n = 1). Surgery due to cancer was performed in 80% of patients (n = 12), 26.7% previously received chemotherapy (n = 6) and 40% radiation therapy (n = 4). Results Sacubitril/valsartan was withdrawn in 2 patients (13.3%) because of dizziness and pruritus respectively. After a mean follow-up of 13 ±8 months, NYHA functional class improved significantly (mean -0.5, p = 0.001), ejection fraction as assassed by echocardiography increased (mean +6.8%, p = 0.018) and NT-proBNP was significantly decreased (mean -1552pg/ml, p = 0.026). There was no significant change in creatinine levels (+0.046 mg/dl, p = 0.564 ). Conclusions In this pilot study we were able to show that sacubitril/valsartan is generally well tolerated in patients with a history of cancer. Patients with cardiotoxicity induced heart failure can be treated and uptitrated with sacubitril/valsartan to usual dosages similarly as in other causes of heart failure. Larger studies are needed to confirm these findings in cancer patients with cardiotoxicity.

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Outcomes of a Pharmacist-Managed Heart Failure Medication Titration Assistance Clinic

Annals of Pharmacotherapy ◽

10.1177/1060028018760568 ◽

2018 ◽

Vol 52 (8) ◽

pp. 724-732 ◽

Cited By ~ 12

Author(s):

Shubha Bhat ◽

Mayank Kansal ◽

George T. Kondos ◽

Vicki Groo

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Ace Inhibitors ◽

Chart Review ◽

Ace Inhibitor ◽

Angiotensin Receptor Blockers ◽

Retrospective Chart Review ◽

National Guidelines ◽

Reduced Ejection Fraction ◽

Receptor Blockers

Background: National guidelines recommend angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and β-blockers (BBs) at target doses for morbidity and mortality benefits in heart failure with reduced ejection fraction (HFrEF); regardless, titration of these therapies in practice remains suboptimal. We implemented an outpatient pharmacist-managed HFrEF medication titration assistance clinic (MTAC) at one institution to improve titration for general cardiology (GC) patients. Objective: To evaluate MTAC impact by determining the proportion of patients on target or maximum tolerated ACE inhibitor/ARB and BB doses. Methods: A retrospective chart review of adult patients with documented ejection fraction ≤40% managed in the MTAC or GC from 2011 to 2013 was conducted. HFrEF medication regimens were collected at initial visit and months 1, 2, 3, 6, 9, and 12 to assess titration. Target doses were defined per guideline or dose at which ejection fraction recovered during the study. Maximum tolerated doses were defined as the highest dose patients tolerated without physiological limitations. Results: Of 148 patients, the MTAC managed 51 and GC managed 97. At baseline, 90% of MTAC versus 82% of GC patients were prescribed ACE inhibitors/ARBs and BBs. In the MTAC, 4% were at target or maximum tolerated doses compared with 32% of GC patients ( P < 0.001). At 12 months, 95% of patients in the MTAC and 87% in GC were prescribed ACE inhibitors/ARBs and BBs. Of those prescribed ACE inhibitors/ARBs and BBs, 64% in the MTAC versus 40% in GC reached target or maximum tolerated doses ( P = 0.01). Conclusions: The pharmacist-managed MTAC increased the proportion of patients on optimal HFrEF therapies and are a resource for GC patients.

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