The reverse remodeling response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction

Martens, Pieter; Beliën, Hanne; Dupont, Matthias; Vandervoort, Pieter M.; Mullens, Wilfried

doi:10.1111/1755-5922.12435

Cited by 147 publications

(148 citation statements)

References 30 publications

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“…Some studies have reported rates as low as 17%, and the majority of studies achieved the maximum dose in less than 50% of individuals . Given that emerging data indicate that the higher doses are associated with superior clinical response, close analyses of the impediments to dose titration in the community are warranted in order to provide guidance on how best this agent in this setting.…”

Section: Discussionmentioning

confidence: 99%

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%

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

et al. 2020

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“…Because of its peculiar phenotype (tachycardia, low blood pressure, LV and/or right ventricular involvement, and dilated ventricles), intervention strategies may be challenging. 87 During the congress, the preliminary results of MADIT-CHIC Study (NCT02164721) by Singh et al 88,89 were also discussed. During the first year of follow-up, echocardiography was conducted every 3 months, then for another 4 years every 6 months, and after that once a year.…”

Section: Treatment Of Cardiotoxicity and New Frontiersmentioning

confidence: 99%

“…There is also a need to investigate the effects and possible benefits of sacubitril/valsartan for the treatment of CTRCM. 87 During the congress, the preliminary results of MADIT-CHIC Study (NCT02164721) by Singh et al 88,89 were also discussed. Thirty patients (87% female) with CTRCM and lymphoma or breast cancer, which qualified for cardiac resynchronizationdefibrillator therapy, participated in the trial.…”

Section: Treatment Of Cardiotoxicity and New Frontiersmentioning

confidence: 99%

Recent advances in cardio‐oncology: a report from the ‘Heart Failure Association 2019 and World Congress on Acute Heart Failure 2019’

et al. 2019

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While anti-cancer therapies, including chemotherapy, immunotherapy, radiotherapy, and targeted therapy, are constantly advancing, cardiovascular toxicity has become a major challenge for cardiologists and oncologists. This has led to an increasing demand of cardio-oncology units in Europe and a growing interest of clinicians and researchers. The Heart Failure 2019 meeting of the Heart Failure Association of the European Society of Cardiology in Athens has therefore created a scientific programme that included four dedicated sessions on the topic along with several additional lectures. The major points that were discussed at the congress included the implementation and delivery of a cardio-oncology service, the collaboration among cardio-oncology experts, and the risk stratification, prevention, and early recognition of cardiotoxicity. Furthermore, sessions addressed the numerous different anti-cancer therapies associated with cardiotoxic effects and provided guidance on how to treat cancer patients who develop cardiovascular disease before, during, and after treatment.

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“…Rather, indirect effects from other beneficial actions of the drug on the entire cardiovascular system might explain the association between diuretic dose changes and sacubitril/valsartan ( Figure ). Indeed, in a real‐world cohort, treatment with sacubitril/valsartan led to significant reverse remodelling of both metrics of systolic and diastolic left ventricular function, as well as a reduction in filling pressures and right ventricular systolic pressures . Of note, lower right ventricular systolic pressure has been shown to be significantly associated with success of loop diuretic down‐titration in patients with stable chronic heart failure .…”

mentioning

confidence: 99%

“…Indeed, in a real-world cohort, treatment with sacubitril/valsartan led to significant reverse remodelling of both metrics of systolic and diastolic left ventricular function, as well as a reduction in filling pressures and right ventricular systolic pressures. 11 Of note, lower right ventricular systolic pressure has been shown to be significantly associated with success of loop diuretic down-titration in patients with stable chronic heart failure. 12 Furthermore, sacubitril/valsartan improved symptoms and physical limitations of heart failure as assessed by the Kansas City Cardiomyopathy Questionnaire, with consistent improvements during follow-up.…”

mentioning

confidence: 99%

Unravelling the effect of sacubitril/valsartan on loop diuretic dosing

Maaten

2019

European J of Heart Fail

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The reverse remodeling response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction

Abstract: Switching therapy in eligible HFrEF patients from a RAS-blocker to sacubitril/valsartan induces beneficial reverse remodeling of both metrics of systolic as diastolic function.

Cited by 147 publications

References 30 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

Recent advances in cardio‐oncology: a report from the ‘Heart Failure Association 2019 and World Congress on Acute Heart Failure 2019’

Unravelling the effect of sacubitril/valsartan on loop diuretic dosing

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