Case Report: Low Dose of Valsartan/Sacubitril Leads to Successful Reversal of Acute Heart Failure in Chemotherapy-Induced Cardiomyopathy.
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ABSTRACT:
SUBMITTER: Lo SH
PROVIDER: S-EPMC7959725 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Case Report: Low Dose of Valsartan/Sacubitril Leads to Successful Reversal of Acute Heart Failure in Chemotherapy-Induced Cardiomyopathy.
Lo Shih-Hsing SH Liu Yi-Ching YC Dai Zen-Kong ZK Chen I-Chen IC Wu Yen-Hsien YH Hsu Jong-Hau JH
Frontiers in pediatrics 20210225
Valsartan/sacubitril is a new agent approved for the treatment of chronic heart failure in adults, with a combination of angiotensin receptor inhibitor and neprilysin inhibitor. However, the benefit of valsartan/sacubitril in pediatric patients is unknown. We herein report its clinical benefit in a case of acute decompensated heart failure in chemotherapy-induced cardiomyopathy. This case suggests that in children with acute heart failure refractory to conventional medications, low dose of sacub ...[more]
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Project description:Abstract Background Cancer therapy–related cardiac dysfunction (CTRCD) is a challenging and life-threatening complication of many chemotherapeutic regimens. CTRCD prevention, diagnosis, and therapy require both careful interdisciplinary assessment and management. For patients with CTRCD, current guidelines of the European Society of Cardiology (ESC) recommend an angiotensin-converting-enzyme inhibitor in combination with a beta-blocker. Recent studies indicate a beneficial effect of sacubitril/valsartan in this patient population. Case summary A 68-year-old female patient with a pleural epithelioid angiosarcoma developed heart failure with reduced ejection fraction and elevated serum biomarkers following doxorubicin treatment. After implementation of a recommended cardioprotective medical therapy including torasemide, ramipril, carvedilol, and spironolactone, the patient suffered two cardiac decompensations within 4 weeks after initiation of a paclitaxel regimen and pleural radiation therapy due to pain exacerbation. Despite a continuous application of the cardioprotective medical treatment regimen, no improvement of left-ventricular ejection fraction (LVEF) was detected in a 4-month follow up. Interestingly, after omitting ramipril and implementing low-dose sacubitril/valsartan (26/24 mg), we observed a decrease in serum biomarkers within 3 months as well as a significant improvement of LVEF within 6 months. After nearly 10 months of disease stabilization under paclitaxel, the patient suffered progressive cancer disease and deceased 1 week later after the initiation of a therapeutic attempt with pazopanib. Discussion This case report highlights the importance of interdisciplinary care in cancer patients as well as the promising role of (low-dose) sacubitril/valsartan in patients with CTRCD even in the setting of delayed initiation.
| S-EPMC9575188 | biostudies-literature
Project description:Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.
| S-EPMC4869613 | biostudies-other
Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess benefits and harms of first‐in‐class angiotensin receptor‐neprilysin inhibitor sacubitril/valsartan (LCZ696) as compared to angiotensin‐converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in chronic heart failure (HF) patients with either reduced, mid‐range, or preserved ejection fraction.
| S-EPMC6984414 | biostudies-literature
Project description:AimsThe study aims to explore the real-world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow-up management system and the effect on the recovery of ventricular remodelling and cardiac function in China.Methods and resultsThis is a single-centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow-up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow-up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12 months. Among the patients, 69.3% were male, with a median age of 49 years. The baseline systolic blood pressure (SBP) was 117.6 ± 18.3 mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1-5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21-34) % vs. 42 (IQR 37.0-54.3) %, P < 0.001], with a great reduction in left atrium diameter [45 (IQR 40.3-51.0) mm vs. 41 (IQR 37.0-45.3) mm, P < 0.001] and LVEDD [65 (IQR 60.0-70.3) mm vs. 55 (IQR 52-62) mm, P < 0.001] during 12 month follow-up. Of patients, 36.5% had a LVEF ≥50%, 54.1% had LVEF >40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12 month follow-up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N-terminal pro-B-type natriuretic peptide (P < 0.001). At Month 12, 50% of patients achieved the target dose of beta-blockers. No serious adverse events caused by sacubitril/valsartan were observed during the follow-up.ConclusionsOptimising HF follow-up management was essential and effective in a real-world clinical setting; the majority could reach the target dose of sacubitril/valsartan within the management system and achieve a remarkable improvement in cardiac function and ventricular remodelling.
| S-EPMC10192287 | biostudies-literature
Project description:BackgroundControversy has persisted over the clinical benefits of low-dose sacubitril/valsartan in patients with heart failure (HF).HypothesisLow-dose sacubitril/valsartan might also be effective and safe in HF patients.MethodsElectronic databases including PubMed, Ovid, and Cochrane Library were systematically retrieved from inception to August 5, 2021. Review manager 5.4 and Stata 15.1 were employed in this systematic review and meta-analysis. Key efficacy outcomes of interest included HF hospitalization, all-cause mortality, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), together with New York Heart Association (NYHA) functional class. The safety outcome was systolic blood pressure (SBP). The grading of recommendations assessment, development, and evaluation approach was conducted to evaluate the quality of evidence for each outcome.ResultsA total of 1269 studies were screened and 9 real-world studies met the inclusion criteria were included in the meta-analysis, with 1697 participants. Compared with low-dose sacubitril/valsartan, high-dose sacubitril/valsartan significantly reduced the risk of HF hospitalization (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.27-0.61, p < .0001) and the risk of all-cause mortality (OR: 0.23, 95% CI: 0.11-0.47, p < .0001). However, there were no appreciable differences in improvements of NYHA (OR: 0.59, 95% CI: 0.15-2.35, p = .45), changes of LVEF (mean difference [MD]: 2.73%, 95% CI: -2.24% to 7.7%, p = .28), changes of NT-proBNP (MD: 43.09, 95% CI: -28.41 to 114.59, p = .24) and changes of SBP (MD: 3.01, 95% CI: -4.62 to 10.64, p = .44) between groups with low-dose and high-dose sacubitril/valsartan.ConclusionsCompared with high-dose sacubitril/valsartan, low-dose sacubitril/valsartan was associated with increased risks of HF hospitalization and all-cause mortality. However, no distinct between-group differences in improvements of NYHA, changes of LVEF, changes of NT-proBNP and changes of SBP were observed.
| S-EPMC10018087 | biostudies-literature
Project description:We tested it in an animal model of myocardial infarction to ensure whether early initiation of dapagliflozin (DAPA), or different orders of combination with sacubitril-valsartan would result in a greater improvement of heart function than sacubitril-valsartan alone in post-myocardial infarction heart failure.
2023-04-13 | GSE229147 | GEO
Project description:BackgroundSacubitril/valsartan, an angiotensin receptor/neprilysin inhibitor (ARNi), improves heart failure (HF) outcomes, yet real-world adherence patterns are not well understood.ObjectivesThe purpose of this study was to analyze longitudinal patterns of adherence to ARNis in patients with HF and to identify factors associated with adherence patterns.MethodsUsing Medicare beneficiaries from 2015 to 2018, we included patients diagnosed with HF who initiated an ARNi. A group-based trajectory model was constructed to identify adherence patterns during follow-up. We used multivariable logistic regression to investigate factors associated with membership in each adherence trajectory group.ResultsAmong 9,475 eligible beneficiaries (age 77 ± 7 years, 34% female), we identified 5 distinct ARNi adherence trajectories, characterized as: immediate discontinuers, who discontinued treatment within the first 3 months (12%); early discontinuers, who discontinued treatment in months 4 to 7 (10%); late discontinuers, who discontinued treatment in months 7 to 10 (12%); intermittently adherent patients (12%); and consistently adherent patients (54%). The first 4 groups were collectively categorized as nonconsistent adherents. Living in a socioeconomically disadvantaged area, ie, a county with the top 20% of Area Deprivation Index (adjusted OR [aOR]: 1.12 [95% CI: 1.00-1.24]) and Black race (aOR: 1.36, [95% CI: 1.18-1.56]) were associated with a higher likelihood of being nonconsistently adherent. Receiving prescriptions from a cardiologist (aOR: 0.64 [95% CI: 0.57-0.73]) was associated with a lower likelihood of suboptimal ARNi adherence.ConclusionsHalf of ARNi users were not consistently adherent to the drug in the first year after treatment initiation. There exist significant racial and socioeconomic inequities in longitudinal adherence to ARNi.
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Project description:ImportanceThe US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (EF) to all patients with HF, noting the greatest benefits in those with below-normal EF. However, the upper bound of below normal is not clearly defined, and value determinations across a broader EF range are unknown.ObjectiveTo estimate the cost-effectiveness of sacubitril-valsartan vs renin-angiotensin system inhibitors (RASis) across various upper-level cutoffs of EF.Design, setting, and participantsThis economic evaluation included participant-level data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and the PARAGON-HF (Prospective Comparison of ARNi with ARB Global Outcomes in HF With Preserved Ejection Fraction) trials. PARADIGM-HF was conducted between 2009 and 2014, PARAGON-HF was conducted between 2014 and 2019, and this analysis was conducted between 2021 and 2023.Main outcomes and measuresA 5-state Markov model used risk reductions for all-cause mortality and HF hospitalization from PARADIGM-HF and PARAGON-HF. Quality-of-life differences were estimated from EuroQol-5D scores. Hospitalization and medication costs were obtained from published national sources; the wholesale acquisition cost of sacubitril-valsartan was $7092 per year. Risk estimates and treatment effects were generated in consecutive 5% EF increments up to 60% and applied to an EF distribution of US patients with HF from the Get With the Guidelines-Heart Failure registry. The base case included a lifetime horizon from a health care sector perspective. Incremental cost-effectiveness ratios (ICERs) were estimated at EFs of 60% or less (base case) and at various upper-level EF cutoffs.ResultsAmong 13 264 total patients whose data were analyzed, for those with EFs of 60% or less, sacubitril-valsartan was projected to add 0.53 quality-adjusted life-years (QALYs) at an incremental lifetime cost of $40 892 compared with RASi, yielding an ICER of $76 852 per QALY. In a probabilistic sensitivity analysis, 95% of the values of the ICER occurred between $71 516 and $82 970 per QALY. Among patients with chronic HF and an EF of 60% or less, treatment with sacubitril-valsartan vs RASis would be at least of economic intermediate value (ICER <$180 000 per QALY) at a sacubitril-valsartan cost of $10 242 or less per year, of high economic value (ICER <$60 000 per QALY) at a cost of $3673 or less per year, and cost-saving at a cost of $338 or less per year. The ICERs were $67 331 per QALY, $59 614 per QALY, and $56 786 per QALY at EFs of 55% or less, 50% or less, and 45% or less, respectively. Treatment with sacubitril-valsartan in only those with EFs of 45% or greater (up to ≤60%) yielded an ICER of $127 172 per QALY gained; treatment was more cost-effective in those at the lower end of this range (ICER of $100 388 per QALY gained for those with EFs of 45%-55%; ICER of $84 291 per QALY gained for those with EFs of 45%-50%).Conclusions and relevanceCost-effectiveness modeling provided an ICER for treatment with sacubitril-valsartan vs RASis consistent with high economic value for patients with reduced and mildly reduced EFs (≤50%) and at least intermediate value at the current undiscounted wholesale acquisition cost price at an EF of 60% or less. Treatment was more cost-effective at lower EF ranges. These findings may have implications for coverage decisions and value assessments in contemporary clinical practice guidelines.
| S-EPMC10534998 | biostudies-literature
Project description:AimsLarge-scale clinical trials have demonstrated clinical benefits of sacubitril-valsartan in symptomatic heart failure with reduced ejection fraction patients (PARADIGM-HF), with potential benefits in patients hospitalized for acute decompensated heart failure (ADHF) (PIONEER-HF) and fewer benefits in patients with heart failure with preserved ejection fraction (PARAGON-HF). The aim of this study was to evaluate eligibility for sacubitril-valsartan using criteria described in PIONNER-HF in non-selected patients hospitalized for ADHF.Methods and resultsBetween November 2014 and May 2019, 799 patients were recruited in a prospective registry of acute heart failure at the University Hospitals of Geneva (ClinicalTrials.gov: NCT02444416). The cohort consists of consecutive patients admitted to the Department of Medicine with ADHF. Eligibility for sacubitril-valsartan was determined using criteria described in PIONEER-HF, including left ventricular ejection fraction, clinical parameters, and co-morbidities. Of 799 patients, 123 (15.39%) were eligible for sacubitril-valsartan treatment. Clinical outcomes including all-cause mortality and readmission were similar in eligible and non-eligible groups, hazard ratio 1.02 (95% confidence interval 0.81-1.29, P = 083).ConclusionsUsing current criteria from randomized controlled trials, only 15% of non-selected patients admitted for ADHF are theoretically eligible for sacubitril-valsartan. Eligibility for sacubitril-valsartan using published criteria is not associated with worse outcome, suggesting that further evaluation of benefits of sacubitril-valsartan in heart failure patients based on parameters other than left ventricular ejection fraction may be of interest.
| S-EPMC7261587 | biostudies-literature
Project description:Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk for HF progression and death. Sacubitril/valsartan (previously known as LCZ696) is a first-in-class medicine that contains a neprilysin (NEP) inhibitor (sacubitril) and an angiotensin II (Ang-II) receptor blocker (valsartan). NEP is an endopeptidase that metabolizes different vasoactive peptides including natriuretic peptides, bradykinin and Ang-II. In consequence, its inhibition increases mainly the levels of both, natriuretic peptides (promoting diuresis, natriuresis and vasodilatation) and Ang-II whose effects are blocked by the angiotensin receptor blocker, valsartan (reducing vasoconstriction and aldosterone release). Results from the 8442 patient PARADIGM-HF study showed in patients with New York Heart Association (NYHA) class II-IV and reduced ejection fraction treated with LCZ696 (versus enalapril), the following benefits: reduction of the risk of death from cardiovascular causes by 20%; reduction of HF hospitalizations by 21%; reduction of the risk of all-cause mortality by 16%. Overall there was a 20% risk reduction on the primary endpoint, composite measure of cardiovascular (CV) death or time to first HF hospitalization. PARADIGM-HF was stopped early after a median follow up of 27 months. Post hoc analyses of PARADIGM-HF as well as the place in therapy of sacubitril/valsartan, including future directions, are included in the present review.
| S-EPMC5076745 | biostudies-literature