Dataset Information

Safety and efficacy of mavacamten for treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized clinical trials.

ABSTRACT:

Background

Mavacamten, an allosteric myosin inhibitor, is considered to be a promising drug for the treatment of hypertrophic cardiomyopathy (HCM). This meta-analysis aimed to explore the safety and efficacy of mavacamten in HCM patients.

Main body

A total number of 539 patients were enrolled in four randomized clinical trials. The mean age of patients was 57.9 years and was followed for 29.3 weeks. Pooled analysis showed a significant improvement in clinical response (Log OR = 0.65; p = 0.01) and the number of patients with a reduction of ≥ 1 NYHA function class (Log OR = 0.64, p = 0.00). It was found that mavacamten did not significantly affect the Kansas City Cardiomyopathy Questionnaire (KCCQ) (SMD = 0.43, p = 0.08), peak oxygen uptake (PVO₂) (SMD = 0.24, p = 0.42), and ejection fraction (EF) (SMD = - 0.65, p = 0.13) as compared with placebo. However, KCCQ (SMD = 0.65, 95% CI 0.44-0.87) and PVO₂ (SMD = 0.49, 95% CI 0.24-0.74) improvements were statically significant in the hypertrophic obstructive cardiomyopathy subgroup (HOCM), and a significant decrease in EF (SMD = -- 1.14, 95% CI - 1.86 to - 0.42) was found in the HOCM subgroup. No significant difference was observed in the incidence rate of serious adverse events between mavacamten and placebo group (Log OR = - 0.23, p = 0.56).

Conclusions

Mavacamten proved to be effective and well-tolerated for the treatment of HCM. Mavacamten improved the signs and symptoms of HOCM and decreased EF in these patients without serious adverse events in the clinical trials.

SUBMITTER: Rabiee Rad M

PROVIDER: S-EPMC9837360 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety and efficacy of mavacamten for treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized clinical trials.

Rabiee Rad Mehrdad M Ghasempour Dabaghi Ghazal G Habibi Danial D

The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology 20230112 1

<h4>Background</h4>Mavacamten, an allosteric myosin inhibitor, is considered to be a promising drug for the treatment of hypertrophic cardiomyopathy (HCM). This meta-analysis aimed to explore the safety and efficacy of mavacamten in HCM patients.<h4>Main body</h4>A total number of 539 patients were enrolled in four randomized clinical trials. The mean age of patients was 57.9 years and was followed for 29.3 weeks. Pooled analysis showed a significant improvement in clinical response (Log OR = 0. ...[more]

PMID: 36633717

Similar Datasets

Project description:BackgroundUnlike other suggested therapies, myosin inhibitors have been shown to change the course of hypertrophic cardiomyopathy by altering the contractile mechanics of cardiomyocytes. This meta-analysis sought to determine the efficacy of mavacamten and aficamten in hypertrophic cardiomyopathy.MethodsThe online databases were searched from inception to July 2024, including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, ClinicalTrials.gov. The meta-analytical data were pooled using risk ratios (RRs) with 95% CI, standard mean difference (SMD) and SE.ResultsA total of 6 randomised controlled trials with 826 hypertrophic cardiomyopathy patients (mean age±SD up to 59.8±14.2 years in intervention vs 60.9±10.5 years in placebo) were included in our study. Of these, 443 received a cardiac myosin inhibitor and 383 received a placebo. The resting left ventricular outflow tract (LVOT) gradient between the two groups was considerably improved by cardiac myosin inhibitors (MD -57.27; 95% CI -63.05 to -51.49). Significant differences were also observed in the post-Valsalva LVOT gradient between the two groups (MD -55.86; 95% CI -65.55 to -46.18). Significantly decreased left ventricle ejection fraction (LVEF) was also seen (MD -4.74; 95% CI -7.22 to -2.26). The New York Health Association (NYHA) class improvement between the two groups also changed significantly (RR 2.21; 95% CI 1.75 to 2.80). Cardiac myosin inhibitors also caused significant improvement in the Kansas City Cardiomyopathy Questionnaire in a Clinical Summary Score between the two groups (MD 7.71; 95% CI 5.37 to 10.05) and significant reduction in the N-terminal pro-B-type natriuretic peptide (SMD -13.27; 95% CI -17.51 to -9.03) and the cardiac troponin I (SMD -11.90; 95% CI -15.07 to -8.72).ConclusionAccording to our meta-analysis, cardiac myosin inhibitors significantly improve the resting and post-Valsalva LVOT gradient, reduce the LVEF and improve the NYHA class and cardiac biomarkers when compared with the placebo.Prospero registration numberCRD52024586161.

Project description:BackgroundThe phase 2 PIONEER-HCM (Phase 2 Open-label Pilot Study Evaluating Mavacamten in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction) study showed that mavacamten improved left ventricular outflow tract gradients, exercise capacity, and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), but the results of longer-term treatment are less well described. We report interim results from the PIONEER-OLE (PIONEER Open-Label Extension) study, the longest-term study of mavacamten in patients with symptomatic obstructive HCM.Methods and resultsPatients who previously completed PIONEER-HCM (n=20) were eligible to enroll in PIONEER-OLE. Patients received oral mavacamten, 5 mg once daily (starting dose), with individualized dose titration at week 6. Evaluations included serial monitoring of safety, echocardiography, Kansas City Cardiomyopathy Questionnaire-Overall Summary Score, and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Thirteen patients enrolled and received mavacamten (median study duration at data cutoff, 201 weeks). Most patients (92.3%) received β-blockers concomitantly. Treatment-emergent adverse events were predominantly mild/moderate. One patient had an isolated reduction in left ventricular ejection fraction to 47%, which recovered and remained normal with continued treatment at a reduced dose. At week 180, mavacamten was associated with New York Heart Association class improvements from baseline (class II to I, n=9; class III to II, n=1; and unchanged, n=2), sustained reductions in left ventricular outflow tract gradients (mean [SD] change from baseline: resting, -50 [55] mm Hg; Valsalva, -70 [41] mm Hg), and serum NT-proBNP levels (median [interquartile range] change from baseline: -498 [-2184 to -76] ng/L), and improved Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (mean [SD] change from baseline: +17 [16]).ConclusionsThis long-term analysis supports the continued safety and effectiveness of mavacamten for >3 years in obstructive HCM.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03496168.

Dataset Information

Safety and efficacy of mavacamten for treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized clinical trials.

Background

Main body

Conclusions

Publications

Safety and efficacy of mavacamten for treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized clinical trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets