Effects of sacubitril/valsartan on functional status and exercise capacity in real-world patients

Lau, Chirik Wah; Martens, Pieter; Lambeets, Seppe; Dupont, Matthias; Mullens, Wilfried

doi:10.1080/00015385.2018.1521054

Cited by 22 publications

(28 citation statements)

References 14 publications

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“…Real world data to complement this impressive clinical trial information are of importance to assess whether response is similar in a community population, who are invariably older and with more comorbidities . To date, the limited published real world data indicate a similar positive experience . Notably however, achievement of TD of sacubitril‐valsartan appears to be more of a challenge in the community.…”

Section: Discussionmentioning

confidence: 99%

“…11,28 To date, the limited published real world data indicate a similar positive experience. [10][11][12]14 Notably however, achievement of TD of sacubitril-valsartan appears to be more of a challenge in the community. Some studies have reported rates as low as 17%, and the majority of studies achieved the maximum dose in less than 50% of individuals.…”

Section: Discussionmentioning

confidence: 99%

“…In the main, observations have been in line with what has been reported in the clinical trial data. [10][11][12][13] However, there has been a lower rate of achievement of the target dose (TD), with the majority of studies reaching TD in less than 50% the patients, 14,15 including a large cohort in Germany. 16 To our knowledge, only one study to date had reported success in titration to TD in greater than 50% of the cases.…”

Section: Introductionmentioning

confidence: 99%

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Sacubitril‐Valsartan in a routine community population: attention to volume status critical to achieving target dose

et al. 2020

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Aims In the PARADIGM‐heart failure trial, sacubitril‐valsartan demonstrated a reduction in heart failure admissions and reduced all‐cause mortality in patients with heart failure with reduced ejection fraction. Although real world data have shown similar benefits regarding efficacy and safety, there has been difficulty in achieving the target dose (TD). The factors preventing the achievement of TD remains unclear. This study assesses the tolerability, ability to achieve, and factors linked to attaining TD in a routine clinical population. Methods and results This is a retrospective single‐centre review of patients switched from angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers to sacubitril‐valsartan between May 2016 and August 2018. Baseline and follow‐up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril‐valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values. To date, a total of 322 patients (75% male patients) have been switched to sacubitril‐valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril‐valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD. Conclusions Sacubitril‐valsartan was well tolerated. Achievement of TD was possible in the majority of the cohort and was linked to response metrics. Reduction in diuretic was required in a large percentage of the population and was the strongest predictor of attaining TD. Therefore, careful clinical attention to volume status assessment is essential to maximising the benefits of sacubitril‐valsartan.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sacubitril‐Valsartan in a routine community population: attention to volume status critical to achieving target dose

et al. 2020

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“…Those CPET variables have been strongly related to HF prognosis and their improvement is well correlated to better outcomes. 9 Additionally, the CPET parameters benefits were also observed in the non-maximal target ARNI dose subgroups.…”

mentioning

confidence: 88%

Terapia com o Inibidor da Neprilisina e do Receptor de Angiotensina e Melhora de Parâmetros de Exercício na Insuficiência Cardíaca com Fração de Ejeção Reduzida

Schwartzmann¹

2020

Arquivos Brasileiros De Cardiologia

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“…Sacubitril/valsartan (S/V) is a treatment for HF with reduced ejection fraction (HFrEF), which impressively impact cardiovascular prognosis by reducing major adverse cardiovascular events such as cardiovascular mortality and sudden death [10]. Moreover, S/V significantly improves cardiopulmonary functional capacity and ventilatory parameters [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Sacubitril/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction

Giallauria¹,

Vitale

Pacileo

et al. 2020

JCM

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Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients’ services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = −0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = −0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = −0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = −2.065, SE = 0.354, p < 0.001). Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.

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Effects of sacubitril/valsartan on functional status and exercise capacity in real-world patients

Cited by 22 publications

References 14 publications

Sacubitril‐Valsartan in a routine community population: attention to volume status critical to achieving target dose

Sacubitril‐Valsartan in a routine community population: attention to volume status critical to achieving target dose

Terapia com o Inibidor da Neprilisina e do Receptor de Angiotensina e Melhora de Parâmetros de Exercício na Insuficiência Cardíaca com Fração de Ejeção Reduzida

Sacubitril/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction

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