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TOPLINE
Treatment with sacubitril-valsartan for 50 weeks in adults with nonobstructive hypertrophic cardiomyopathy (nHCM) and reduced exercise capacity did not improve peak oxygen uptake (pVO2) but was associated with reductions in interventricular septal thickness and the left ventricular mass index.
METHODOLOGY
- Researchers conducted a double-blind randomized trial across six countries between January 2020 and May 2024 to assess the safety and tolerability of sacubitril-valsartan and its effect on exercise capacity in adults with nHCM.
- They included adults with nHCM and reduced exercise capacity (pVO2 ≤ 80% predicted). Patients had a mean age of 55.8 years; 77.5% were men, and 80% had New York Heart Association functional class II symptoms.
- After a 4-week single-blind run-in with placebo followed by sacubitril-valsartan, 40 patients were randomly assigned to receive either sacubitril-valsartan (uptitrated to 200 mg twice daily) or matching placebo in a double-blind manner.
- The primary endpoint was the change from baseline in pVO2, measured using cardiopulmonary exercise testing, at week 50. Secondary endpoints included safety and tolerability.
- Exploratory endpoints included cardiac structure and function, assessed using echocardiography; serum biomarkers of heart failure; and a composite z-score of clinically important nHCM parameters.
TAKEAWAY
- Patients who received sacubitril-valsartan and those who received placebo did not have a significant difference in pVO2 at 50 weeks. Treatment compliance was 96% in both groups.
- Compared with patients who received placebo, those who received sacubitril-valsartan had a 4.7-mm reduction in interventricular septal thickness (P = .0001) and a 22.5-g/m2 reduction in the left ventricular mass index (P = .02).
- The composite z-score of cardiac parameters improved in patients who received sacubitril-valsartan vs those who received placebo (P = .015).
- Three serious adverse events occurred, all of which were in the sacubitril-valsartan group, but none were drug-related; hypotension-related events were more frequent with the drug. No deaths were reported.
IN PRACTICE
"Whether the magnitude of remodeling observed with LCZ696 [sacubitril-valsartan] translates into improved clinical outcomes in nHCM remains uncertain," the researchers wrote.
SOURCE
The study was led by Milena Petranovic, MD, of Massachusetts General Hospital in Boston. It was published online on August 19 in JACC: Heart Failure.
LIMITATIONS
The study had a small sample size, which may have limited the ability to detect changes of smaller magnitude. The study had a relatively low proportion of women. Researchers used echocardiography and could not assess myocardial fibrosis.
DISCLOSURES
The study was funded by Novartis. One author received fellowship support from Novartis. Several authors reported consulting fees, research support, or employment relationships with pharmaceutical companies, including Novartis. Detailed author disclosures are reported in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
