What question did this study set out to answer?

To evaluate the efficacy and safety of cardiac myosin inhibitors, specifically mavacamten and aficamten, in patients with symptomatic hypertrophic cardiomyopathy.

January 15, 2025Frontiers in Cardiovascular MedicineOpen Access

Efficacy and safety of cardiac myosin inhibitors for symptomatic hypertrophic cardiomyopathy: a meta-analysis of randomized controlled trials

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Why the study?

Traditional treatments for hypertrophic cardiomyopathy address symptoms rather than the underlying disease mechanism, highlighting the need for novel therapies like cardiac myosin inhibitors.

Do cardiac myosin inhibitors (mavacamten and aficamten) improve symptoms and reduce LVOT gradients in patients with symptomatic hypertrophic cardiomyopathy compared to placebo?

Key Points

To evaluate the efficacy and safety of cardiac myosin inhibitors, specifically mavacamten and aficamten, in patients with symptomatic hypertrophic cardiomyopathy.
Conducted a systematic review and meta-analysis of randomized controlled trials following PRISMA guidelines.
Identified and analyzed six randomized placebo-controlled trials comprising 826 total participants.
Evaluated clinical endpoints including NYHA functional class, KCCQ-CSS scores, LVOT gradients, LVEF, and adverse event frequencies.
Cardiac myosin inhibitors significantly improved NYHA functional class and KCCQ-CSS summary scores compared with placebo.
Incidence of treatment-emergent adverse events and serious adverse events was comparable between the myosin inhibitor and placebo arms, with no significant difference reported.

Structured PICO

Do cardiac myosin inhibitors (mavacamten and aficamten) improve symptoms and reduce LVOT gradients in patients with symptomatic hypertrophic cardiomyopathy compared to placebo?

Population

826 participants with symptomatic hypertrophic cardiomyopathy (HCM) from 6 RCTs, mean age spanning 51 to 60.9 years, predominantly male (427 men, 399 women).

Intervention

Cardiac myosin inhibitors (mavacamten or aficamten) as a class.

Comparator

Placebo.

Outcome

Improvement in NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), LVOT gradients, and left ventricular ejection fraction (LVEF).patient reported

Cardiac myosin inhibitors (mavacamten and aficamten) significantly improve NYHA functional class, KCCQ-CSS, and reduce LVOT gradients in patients with symptomatic hypertrophic cardiomyopathy, with a safety profile comparable to placebo.

Limitations

Variability in follow-up periods across the studies
Heterogeneous designs and patient populations (5 RCTs on oHCM, 1 on nHCM)
Inability to stratify data for obstructive and non-obstructive HCM separately
Lack of data on the effects of mavacamten and aficamten on left ventricular diastolic function
None of the included trials reported data on the discontinuation of medication due to decreased ejection fraction
Lack of comprehensive evaluation of long-term effects on clinical outcomes such as mortality and sudden cardiac death risk

Implication

Supports myosin inhibitor use in symptomatic oHCM; confirms and extends RCT evidence on gradient reduction and symptoms.

Abstract

Introduction: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder. It is characterized by left ventricular hypertrophy and impaired cardiac function, with forms categorized into obstructive (oHCM) and nonobstructive (nHCM). Traditional treatments address symptoms but not the underlying disease mechanism, highlighting the need for novel therapies. Cardiac myosin inhibitors such as mavacamten and aficamten present potential new treatment options. Methods: A meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA guidelines. Studies comparing cardiac myosin inhibitors with placebo were reviewed, and outcomes related to NYHA functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), LVOT gradients, and left ventricular ejection fraction (LVEF) were analyzed. Results: Six RCTs involving 826 participants demonstrated that mavacamten and aficamten significantly improved NYHA functional class and KCCQ-CSS scores. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) was similar between the treatment and control groups, indicating a comparable safety profile. Conclusion: Cardiac myosin inhibitors are effective in improving cardiac function and reducing LVOT obstruction in HCM patients. They offer a promising alternative to current treatments, with a safety profile comparable to placebo. Further research is needed to confirm long-term benefits.