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Cardiac Myosin Inhibitors for Obstructive Hypertrophic Cardiomyopathy: A Meta-analysis of Randomized
Nicole Felix1, Larissa Teixeira2, Alleh Nogueira3
1Federal University of Campina Grande, 795 Juvêncio Arruda Avenue, Campina Grande, Brazil. nicole.santos@estudante.ufcg.edu.br.
Insights
Cardiac myosin inhibitors (CMI) improve functional class and reduce left ventricular outflow tract gradients in obstructive hypertrophic cardiomyopathy (oHCM). However, they increase the risk of reduced left ventricular ejection fraction, though benefits outweigh risks.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Cardiac myosin inhibitors (CMI) are a novel, non-invasive therapy for hypertrophic cardiomyopathy.
- The efficacy and safety of CMI in obstructive hypertrophic cardiomyopathy (oHCM) require further investigation, particularly regarding secondary endpoints in randomized controlled trials (RCTs).
Purpose of the Study:
- To systematically evaluate the efficacy and safety of CMI in patients with oHCM by analyzing data from RCTs.
- To assess the impact of CMI on clinical and hemodynamic parameters, as well as potential adverse events.
Main Methods:
- Systematic literature search of PubMed, Embase, Web of Science, and Clinicaltrials.gov for RCTs comparing CMI with placebo in oHCM patients.
- Random-effects model applied to evaluate efficacy and safety outcomes, including primary and secondary endpoints.
Main Results:
- Five RCTs with 767 patients were included; 402 received CMI.
- CMI significantly improved New York Heart Association (NYHA) functional class (RR 2.33) and reduced resting and provoked left ventricular outflow tract (LVOT) gradients.
- CMI increased the risk of left ventricular ejection fraction <50% (RR 4.80), affecting 8% of patients, but a class effect was observed, with benefits outweighing risks.
Conclusions:
- Cardiac myosin inhibitors (mavacamten, aficamten) represent a class effect that improves clinical and hemodynamic endpoints in oHCM patients.
- Despite an increased incidence of reduced left ventricular ejection fraction, the overall benefit-risk profile favors CMI use in oHCM.
Background:
Cardiac myosin inhibitors (CMI) have emerged as the first disease-specific, noninvasive therapy with promising results in patients with hypertrophic cardiomyopathy. However, its role in obstructive hypertrophic cardiomyopathy (oHCM) remains uncertain, especially in secondary endpoints of randomized controlled trials (RCTs).
Methods:
We systematically searched PubMed, Embase, Web of Science, and Clinicaltrials.gov from inception to June 2024 for RCTs comparing CMI versus placebo in patients with oHCM. We applied a random-effects model to evaluate efficacy and safety outcomes and primary or secondary outcomes of RCTs.
Results:
We included five RCTs comprising 767 patients, of whom 402 (52.5%) were randomized to CMI. Relative to placebo, CMI were associated with a higher rate of improvement of at least one New York Heart Association (NYHA) functional class [risk ratio (RR) 2.33; 95% confidence interval (CI) 1.92-2.82]. In addition, CMI reduced resting left ventricular outflow tract (LVOT) [mean difference (MD) - 42.51 mmHg; 95% CI - 59.27 to - 25.75] and the provoked LVOT gradients (MD - 46.12 mmHg; 95% CI - 55.70 to - 36.54). However, CMI significantly increased the risk of reaching a left ventricular ejection fraction below 50% (RR 4.80; 95% CI 1.42-16.20), affecting 8% of patients during long-term follow-up of up to 120 weeks. There was no significant interaction across subgroups of class representatives, pointing to a class effect. The benefit-risk analysis indicated a larger benefit for NYHA class improvement than risk for systolic dysfunction.
Conclusion:
In patients with oHCM, mavacamten and aficamten as a class improve clinical and hemodynamic endpoints compared with placebo, albeit with a higher incidence of a reduction in left ventricular ejection fraction.
Registration:
PROSPERO CRD42023468079.
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