Key result
Sacubitril/valsartan fails to improve peak oxygen uptake over placebo but reduces septal thickness by ~5 mm.
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Why the study?
Developing effective therapy for symptomatic nonobstructive hypertrophic cardiomyopathy is a major unmet need, and sacubitril/valsartan has proven beneficial in heart failure but had not been evaluated for nHCM.
Does sacubitril/valsartan improve peak oxygen uptake in adult patients with nonobstructive hypertrophic cardiomyopathy and reduced exercise capacity?
RCT (n=40)
Double-blind
1:1
Yes
Does sacubitril/valsartan improve peak oxygen uptake in adult patients with nonobstructive hypertrophic cardiomyopathy and reduced exercise capacity?
Sacubitril/valsartan did not improve exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy, but it significantly reduced interventricular septal thickness and left ventricular mass index, suggesting favorable structural remodeling.
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“Because LV hypertrophy has been associated with a higher risk of cardiovascular events, arrhythmias and mortality, even modest reductions in LV mass and wall thickness may be interpreted as favorable. However, whether the magnitude of remodeling observed with LCZ696 translates into improved clinical outcomes in nHCM remains uncertain.”
Provides early evidence that sacubitril/valsartan may favorably reduce left ventricular mass in.
BackgroundDeveloping effective therapy for symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM) is a major unmet need. Sacubitril/valsartan (LCZ696) is an angiotensin II receptor-neprilysin inhibitor that increases circulating natriuretic peptides and has proven to be beneficial in heart failure but has not been evaluated for nHCM. ObjectivesThis phase II, multicenter, double-blinded, randomized, placebo-controlled clinical trial assessed the safety, tolerability, and efficacy of LCZ696 in improving exercise capacity in patients with nHCM. MethodsAdult patients with nHCM and reduced exercise capacity (% predicted peak oxygen consumption ≤80%) were randomized 1:1 to placebo or LCZ696 (uptitrated to 200 mg twice daily). The primary endpoint was change from baseline in peak oxygen uptake (pVO2) as measured by cardiopulmonary exercise testing after 50 weeks. Additional analyses included changes in echocardiographic features, heart failure serum biomarkers, and standardized changes in clinically important nHCM parameters as a single composite z-score. ResultsForty participants (median age: 57.5 years; 80% NYHA functional class II; mean % predicted pVO2: 67.7%) were randomized. There was no difference in change from baseline in pVO2 between LCZ696 and placebo (P = 0.55). Interventricular septal thickness decreased by 4.7 mm (P = 0.0001) and left ventricular mass index decreased by 22.5 g/m2 (P = 0.02) at 50 weeks in LCZ696 compared with the placebo. Composite z-score also improved in the LCZ696 group (P = 0.015), driven by changes in wall thickness, left ventricular mass index, and troponin. Rates of mild to moderate hypotension and mild renal impairment were similar to those observed in prior LCZ696 studies in heart failure. ConclusionsAlthough LCZ696 treatment did not improve pVO2 after 50 weeks, the favorable cardiac structural remodeling suggests a potential benefit in this patient group.
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Petranović et al. (2025) conducted an RCT in Non-obstructive hypertrophic cardiomyopathy (nHCM) (n=40). Sacubitril/valsartan (LCZ696) vs. Placebo was evaluated on Change from baseline in peak oxygen uptake (pVO2) as measured by cardiopulmonary exercise testing after 50 weeks (p=0.55). Sacubitril/valsartan did not improve peak oxygen uptake compared to placebo at 50 weeks (P=0.55), but significantly decreased interventricular septal thickness by 4.7 mm (P=0.0001).
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