PMID- 37453852 OWN - NLM STAT- MEDLINE DCOM- 20231006 LR - 20240318 IS - 1444-2892 (Electronic) IS - 1443-9506 (Linking) VI - 32 IP - 9 DP - 2023 Sep TI - Efficacy and Safety of Mavacamten in the Treatment of Hypertrophic Cardiomyopathy: A Systematic Review. PG - 1049-1056 LID - S1443-9506(23)03627-2 [pii] LID - 10.1016/j.hlc.2023.05.019 [doi] AB - BACKGROUND: Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We aim to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive HCM. METHODS: This systematic review of the literature followed the PRISMA guidelines. Title/abstract and topics were searched using the following term: "mavacamten". The electronic research literature databases included the Cochrane Library, MedLine, and clinicaltrials.gov from July to August 2022. Primary efficacy endpoint was to assess clinical response at the end of treatment compared with baseline, defined as, at least one New York Heart Association (NYHA) class reduction. Two secondary endpoints from baseline were determined. The first was defined as improvement in mixed venous oxygen pressure (pVO(2)). The second was defined as reduction of the post-exercise left ventricular outflow tract (LVOT) gradient. RESULTS: We included in our analyses data from four studies that met our review eligibility criteria. There were three randomised placebo-controlled clinical trials and one non-randomised open-label clinical trial. All four studies showed a reduction in NYHA class from mavacamten use. Three out of four studies demonstrated >1 NYHA functional class improvement ranging from 34% to 80%, while only one study showed a smaller percentage of patients remaining at class 3. Three out of four studies measured pVO(2) as an outcome, and all three studies noticed an increase in peak oxygen consumption after mavacamten treatment. Additionally, three out of four studies measured post-exercise LVOT gradient reduction as an outcome and all three found significant reduction in the post-exercise LVOT gradient after treatment. The most commonly observed adverse side effects were atrial fibrillation and decreased left ventricular ejection fraction, but all participants recovered without long-term sequelae and only one patient dropped out of the trial. CONCLUSIONS: Mavacamten has a greater efficacy than placebo in the treatment of HCM. It also showed promising tolerability and efficacy profiles in the treatment of HCM in adults. The three endpoints used in the evaluation of studies were reduction in NYHA class, increase in pVO(2), and post-exercise LVOT gradient reduction. Mavacamten showed greater reduction in NYHA, larger effects on increase of pVO(2), and significant reduction of the LVOT gradient. Mavacamten was also found to be well tolerated, like the placebo. The side effect profile was limited for the majority of individuals taking mavacamten. In the future, authors recommended dose-optimisation studies, and studies that evaluate mavacamten both in comparison to, and in conjunction with other current treatments. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Bishev, Daniel AU - Bishev D AD - University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL, USA; HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA; HCA Florida North Florida Hospital, Gainesville, FL, USA. FAU - Fabara, Stephanie AU - Fabara S AD - University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL, USA; HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA; HCA Florida North Florida Hospital, Gainesville, FL, USA. Electronic address: stephanie.fabarapino@hcahealthcare.com. FAU - Loseke, Isaac AU - Loseke I AD - University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL, USA; HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA; HCA Florida North Florida Hospital, Gainesville, FL, USA. FAU - Alok, Akankcha AU - Alok A AD - University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL, USA; HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA; HCA Florida North Florida Hospital, Gainesville, FL, USA. FAU - Al-Ani, Hashim AU - Al-Ani H AD - University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL, USA; HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA; HCA Florida North Florida Hospital, Gainesville, FL, USA. FAU - Bazikian, Yvette AU - Bazikian Y AD - University of Central Florida College of Medicine, Graduate Medical Education, Orlando, FL, USA; HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA; HCA Florida North Florida Hospital, Gainesville, FL, USA. LA - eng PT - Journal Article PT - Review PT - Systematic Review DEP - 20230714 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 RN - 0 (MYK-461) SB - IM MH - Adult MH - Humans MH - *Cardiomyopathy, Hypertrophic/drug therapy/complications MH - Heart MH - Stroke Volume MH - *Ventricular Function, Left MH - Clinical Trials as Topic OTO - NOTNLM OT - Cardiac muscle OT - Hypertrophic obstructive cardiomyopathy OT - Mavacamten OT - Myosin inhibitor EDAT- 2023/07/16 01:06 MHDA- 2023/10/06 06:43 CRDT- 2023/07/15 21:59 PHST- 2023/02/02 00:00 [received] PHST- 2023/05/25 00:00 [revised] PHST- 2023/05/29 00:00 [accepted] PHST- 2023/10/06 06:43 [medline] PHST- 2023/07/16 01:06 [pubmed] PHST- 2023/07/15 21:59 [entrez] AID - S1443-9506(23)03627-2 [pii] AID - 10.1016/j.hlc.2023.05.019 [doi] PST - ppublish SO - Heart Lung Circ. 2023 Sep;32(9):1049-1056. doi: 10.1016/j.hlc.2023.05.019. Epub 2023 Jul 14.