Efficacy of aficamten in obstructive hypertrophic cardiomyopathy: A systematic review and meta-analysis

Le résumé fourni par la source

Obstructive hypertrophic cardiomyopathy (oHCM), a morbid hereditary condition, is characterized by asymmetrical intraventricular septum enlargement, obstructing blood flow from the left ventricle outflow tract (LVOT) and lowering cardiac output. Aficamten, a novel selective, oral myosin inhibitor, has been suggested to reduce myocardial hypercontractility and decrease LVOT gradient in oHCM. A comprehensive search was conducted through PubMed, Embase, Scopus, and Cochrane databases for relevant literature from inception up to May 2024. Six studies focusing on efficacy and safety aficamten was included. Pooled outcome estimates were reported as mean difference (MD) and 95 % CI using random effect model. Statistical heterogeneity was assessed using I 2 and X 2 statistics. We found a significant change of −143.23 (pg/ml) NT-proBNP [95 % CI −564.8 to 278.4, I 2 = 97.65 %, P < 0.001], −50.9 mmHg Valsalva LVOT gradient [95 % CI −55.2 to −46.6, I 2 = 0 %, P = 0.44], −38.5 mmHg resting LVOT gradient [95 % CI −49.9 to −27.6, I 2 = 0 %, P = 0.64], −5.98 % mean LVEF [95 % CI −9.4 to −2.6, I 2 = 64.18 %, P = 0.06] and −2.32 (ng/dl) Hs-Troponin I [95 % CI −7.55 to −2.91, I 2 = 0 %, P = 0.97] from the baseline. We found significant 64.9 % ≥ 1 NYHA class improvement [95 % CI 45.8 %–84.1 %, I 2 = 90.6 %, P < 0.001] in aficamten. There was ‘low’ overall risk of bias in included studies. We found that aficamten significantly reduced myocardial stress surrogates and functional disability parameters. The small sample sizes, diverse study designs and single-arm analysis limit our findings. More robust trials with larger sample sizes are required to establish conclusive evidence.

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