Sacubitril/valsartan fails to show significant post-MI remodeling benefits vs. valsartan
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Sacubitril/valsartan failed to demonstrate significant reverse remodeling effect compared with valsartan among patients with asymptomatic left ventricular systolic dysfunction following MI, a speaker reported.
According to findings of the randomized controlled trial presented at the virtual Heart Failure Society of America Scientific Meeting, sacubitril/valsartan (Entresto, Novartis) also did not significantly reduce levels of N-terminal pro-B-type natriuretic peptide or high-sensitivity troponin and increased levels of atrial natriuretic peptide compared with valsartan.
Both treatments were well tolerated by the cohort. There was a greater prevalence of symptomatic hypertension among patients taking sacubitril/valsartan, but it did not warrant discontinuation.
“These findings do not support any beneficial effects of the addition of neprilysin inhibition to current standard of care on cardiac structure and function in this patient population,” Kieran F. Docherty, PhD student and clinical lecturer at the institute of cardiovascular and medical sciences at the University of Glasgow, U.K., said during his presentation.
For this trial, investigators randomly assigned 93 patients who had experienced an MI and had LV ejection fraction of at least 40% to sacubitril/valsartan or valsartan. The primary outcome was change in LV end systolic volume index from baseline to 12 months as measured by cardiac MRI. Secondary outcomes included change in NT-proBNP, change in high-sensitivity troponin levels and change in LV end systolic volume index, left atrial volume index, LVEF and LV mass index.
Investigators observed a –4 mL/m2 drop in LV end systolic volume index in patients on sacubitril/valsartan compared with a –2 mL/m2 among those on valsartan (between-group difference, –1.9 mL/m2; 95% CI, –4.9 to 1; P = .19).
Additionally, patients on sacubitril/valsartan did not experience any significant reduction in NT-proBNP (between group difference, –14.6%; 95% CI, –37.1 to 15.9; P = .31) or high-sensitivity troponin (between group difference, –13.2%; 95% CI, –38.4 to 22.2; P = .41) compared with those on valsartan.
Investigators found no significant difference between the groups in LV end systolic volume index (P = .1), left atrial volume index (P = .29), LVEF (P = .46) or LV mass index (P = .16) at 12 months.
Moreover, in an exploratory analysis, patients on sacubitril/valsartan experienced increased levels of atrial natriuretic peptide compared with patients on valsartan (between-group difference, 0.13 ng/mL; 95% CI, 0.03-0.22; P = .013).
“This was a rigorously executed randomized controlled trial with very high endpoint ascertainment,” James E. Udelson, MD, chief of the division of cardiology and director of the nuclear cardiology laboratory at Tufts Medical Center and professor at the Tufts University School of Medicine, said during his discussant presentation. “The neutral results should be seen within the context of sample sizing and the follow-up duration, ruling out a large end systolic volume change over 12 months. However, it is possible and indeed plausible that sacubitril/valsartan favorably effects late post-MI remodeling and potentially outcomes but requires a larger sample size with longer duration to be demonstrable.”
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Docherty K, et al. Late-breaking clinical trials II. Presented at: Heart Failure Society of America Scientific Meeting; Sept. 30-Oct. 6, 2020 (virtual meeting).
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