Clinical InvestigationsSacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study
Section snippets
Study design
The study was previously registered on ClinicalTrials.gov under the number NCT03190304. This is a single-center, randomized, double-blind, active-controlled study comparing head-to-head the effect of sacubitril/valsartan and enalapril on exercise tolerance in participants with HFrEF. This clinical trial was approved by the local ethics committee (4487-16-153), and all participants provided written informed consent. We followed the CONSORT checklist for randomized clinical trials.10
The study
Results
At baseline, physical and clinical characteristics as well as medications and their respective doses are described in Table I. Particularly, at baseline, ACEI (sacubitril/valsartan group = 24 ± 15 mg and enalapril group = 18 ± 12 mg; P .181) and ARB (sacubitril/valsartan group = 79 ± 33 mg and enalapril group = 75 ± 35 mg; P= .884) doses were similar between groups. At 12 weeks, the mean dose of sacubitril/valsartan was 382.6 ± 57.6 mg daily and enalapril 34.4 ± 9.2 mg daily. At 24 weeks, the
Discussion
To the best of our knowledge, this is the first randomized, double-blind, active-controlled trial evaluating the effect of sacubitril/valsartan and enalapril on maximal exercise capacity (peak VO2) in patients with HFrEF. We found an increase in peak VO2 (approximately 13%) in both groups, but with no statistical and clinical differences between them. Similarly, although we found an increase in 6-MWT at 12 and 24 weeks within groups, we did not observe statistical differences after treatments
Conclusion
Amongst patients with HFrEF previously receiving an ACEI and/or ARB, switching them to sacubitril/valsartan did not substantially improve peak VO2 or 6-MWT after 12 or 24 weeks. Neither were substantial differences in the effects on other measurements observed, including skeletal muscle blood flow, cardiac function and structure, muscle strength, body composition, and quality of life. The trial was not adequately powered to show modest differences but suggests that clinically meaningful effects
Competencies in medical knowledge
This study shows that sacubitril/valsartan or enalapril did not significantly improve peak VO2 and 6-MWT after 12 or 24 weeks in participants with HFrEF.
Translational outlook
A larger sample size and longer follow-up study with older and more severe patients with HFrEF should investigate the possible beneficial effects of both treatments on exercise capacity and its pathophysiological mechanisms.
Disclosures
The authors declare that there are no conflicts of interest.
Funding
This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2016/24833-0). M.R.S. by FAPESP (2016/24306-0 and 2019/14938-7). C.E.N. by Conselho Nacional de Pesquisa e Desenvolvimento (CNPq; 303573/2015-5). A.C.P.B. by FAPESP (2016/24833-0).
Data sharing
Unidentified individual participant data and data analysis plan are available from the corresponding author upon reasonable request.
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Renin-angiotensin-aldosterone system inhibition in patients affected by heart failure: efficacy, mechanistic effects and practical use of sacubitril/valsartan. Position Paper of the Italian Society of Cardiology
2022, European Journal of Internal MedicineCitation Excerpt :A first pilot study [46] in 58 HFrEF patients initiating sacubitril/valsartan, reported an improvement in 6MWT distance after 30 days of treatment (+13.9%). However, a more recent study [47] conducted in 52 patients, confirmed the improvement of exercise capacity after initiation of sacubitril/valsartan, but no differences in peak VO2 or 6MWT distance were observed vs enalapril after 12 and 24 weeks. An impairment of glomerular filtration rate (GFR) is frequent in HF and is associated with higher rates of mortality and CV events [48,49].
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