Heart failure & cardiomyopathies
Safety and efficacy of mavacamten in obstructive versus non-obstructive hypertrophic cardiomyopathy: a meta-analysis of randomised controlled trials
Pooled result · NYHA class improvement in oHCMResult — go to the resultOdds ratio 4.94 95% CI 3.25–7.49Authors' conclusion
Mavacamten appears effective in oHCM, improving symptoms and obstruction with a reassuring safety profile. In nHCM, it drives biochemical and structural remodelling without conferring meaningful symptomatic benefit, while potentially posing a considerably elevated risk of clinically relevant systolic dysfunction. These findings support phenotype-guided precision therapy, urging stringent echocardiographic surveillance and caution regarding off-label use in non-obstructive disease.
Study context
- Population
- Adults with hypertrophic cardiomyopathy (HCM)Obstructive HCM (oHCM) 444 · nHCM 639
- Participants
- 1,083 adults · 5 randomised controlled trials (RCTs)
- Comparison
- obstructive HCM vs non-obstructive HCM
Methodological detailsrandom-effects models, stratified by phenotype, RoB-2, trial sequential analysis, Grading of Recommendations, Assessment, Development and Evaluation (GRADE)
- Random-effects models
- Stratified by phenotype
- RoB-2
- Trial sequential analysis
- GRADE
Pooled result
New York Heart Association (NYHA) class improvement in oHCM
Odds ratio
4.94
95% CI 3.25–7.49
As reported in the abstract
Further pooled results
Functional benefit and KCCQ-CSS in nHCM
| Comparison | MD (95% CI) | |
|---|---|---|
| Mavacamten · nHCM; suggestive KCCQ-CSS worsening | −0.70 (−1.26 to −0.14) | |
| −2−101Difference (linear scale) |
| Outcome | MD |
|---|---|
| KCCQ-CSS in oHCM · oHCM | 8.99 |
LVOT gradient in oHCM
- Substantial LVOT gradient reductions
Functional benefit and KCCQ-CSS in nHCM
- nHCM patients showed no functional benefit
Biomarkers (NT-proBNP, hs-cTnI)
- Decreased substantially across both phenotypes
Safety
Left ventricular ejection fraction declining <50%
| Comparison | OR (95% CI) | |
|---|---|---|
| Mavacamten | 14.35 (5.92–34.77) | |
| Mavacamten · oHCM; not elevated | 2.08 (0.79–5.48) | |
| 0.050.21520Odds ratio (log scale) |
- Left ventricular ejection fraction declining <50%: nHCM; based on limited events, requiring cautious interpretation
- Left ventricular ejection fraction declining <50%: Serious adverse events did not increase overall in either phenotype.
Original publication
Summarised from the published abstract; every number is checked against it