Impact of Sacubitril/Valsartan Treatment on Left Ventricular Reverse Remodeling
A meta-analysis evaluated the effect of sacubitril/valsartan on echocardiographic parameters (not only) in patients with HFrEF. The authors focused on both the presence and significance of changes, as well as the speed of their onset after the initiation of treatment.
Introduction
Remodeling of the heart atria and ventricles, which develops in many cardiovascular diseases, especially due to disrupted neurohumoral regulation, is a significant pathophysiological mechanism associated with higher morbidity and mortality in patients with heart failure.
The first angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril/valsartan, has shown a significant impact on reducing cardiovascular mortality and the number of rehospitalizations in patients with heart failure with reduced ejection fraction (HFrEF). The studies with ARNI reported effects in terms of reverse remodeling (i.e., favorable changes in the dimensions, volume, and shape of the heart atria and ventricles) after the beginning of treatment. However, the results regarding specific parameters, timing, or impact of the dosage were varied. Therefore, a meta-analysis focusing on the changes in echocardiographic parameters, biomarkers, and functional capacity in patients treated with sacubitril/valsartan was published in the prestigious Journal of the American Heart Association in July 2019.
Analyzed Studies
The aim of the study was to compare the impact of sacubitril/valsartan on the aforementioned parameters with that of angiotensin-converting enzyme inhibitors (ACEi) or sartans. From works published between 2010 and 2019, a total of 20 studies were selected for the final analysis, encompassing a total of 10,175 patients. Four of these were randomized clinical trials, considered the highest quality evidence, while the rest were high-quality cohort and observational studies. Parameters quantifying reverse remodeling were evaluated echocardiographically in 19 studies and by magnetic resonance in 1 study.
Findings
Treatment with ARNI in patients with HFrEF led to significant improvements in functional capacity defined by both the NYHA symptom classification and the 6-minute walk test results. ARNI also showed substantially more significant changes in parameters describing reverse remodeling of the heart sections compared to ACEi/sartans, particularly concerning left ventricular ejection fraction (LVEF), end-systolic and end-diastolic dimensions (ESD, EDD), and volumes (ESV, EDV). Positive changes in the parameters were observed as early as 3 months post-treatment inception and became more pronounced with longer observation periods, up to 12 months.
In contrast, for patients with heart failure with preserved ejection fraction (HFpEF), who were included in only 1 of the enrolled studies, comprising 301 participants, no significant differences in the impact of the treatment approaches on the studied parameters were observed, except for the left ventricular mass index (LVMI) and left atrial volume.
Conclusion
The meta-analysis concluded that the impact of sacubitril/valsartan from the ARNI group on improving the functional capacity of patients with HFrEF and on reverse remodeling of the heart sections, especially on the dimensions and hypertrophy of the left ventricle, is more significant than that of ACE inhibitors or sartans. This effect is quickly noticeable, long-lasting, and increases over time, suggesting greater benefits with early initiation of sacubitril/valsartan treatment.
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Sources: Wang Y., Zhou R., Lu C. et al. Effects of the angiotensin-receptor neprilysin inhibitor on cardiac reverse remodeling: meta-analysis. J Am Heart Assoc 2019 Jul 2; 8 (13): e012272, doi: 10.1161/JAHA.119.012272.
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