Dahlberg Sarah, Chang Ellen T, Weiss Sheila R, Dopart Pamela, Gould Errol, Ritchey Mary E
Exponent, Inc, Menlo Park, CA, 94025, USA.
Currax Pharmaceuticals LLC., Brentwood, TN, 37027, USA.
Diabetes Metab Syndr Obes. 2022 Sep 29;15:3049-3067. doi: 10.2147/DMSO.S381652. eCollection 2022.
Naltrexone/Bupropion extended release (ER; Contrave) is an extended-release, fixed-dose combination medication of naltrexone (8 mg) and bupropion (90 mg) for patients with obesity or overweight with at least one weight-related comorbidity. Obese and overweight patients with or without comorbidities are at increased cardiovascular (CV) risk. Due to the increased CV risk profile in this patient population, this systematic literature review was conducted to assess human studies reporting major adverse CV events (MACE) and other CV events. eligibility criteria included clinical studies (randomized and observational) published from January 1, 2012, to September 30, 2021, with data comparing users of naltrexone/bupropion ER, naltrexone with bupropion, bupropion without naltrexone, or naltrexone without bupropion versus comparator groups (placebo or other treatments), and with sufficient information to determine the frequency of MACE or other CV adverse events by treatment group. Among 2539 English-language articles identified, 70 articles met the eligibility criteria: seven studies of naltrexone/bupropion ER or naltrexone with bupropion, 32 studies of bupropion, and 31 studies of naltrexone. No studies reported an increased risk of MACE among users of naltrexone/bupropion ER, naltrexone with bupropion, or bupropion or naltrexone individually compared with nonusers. One-half of the available studies (n = 35) reported no (zero) CV events and the other half (n = 35) reported that a non-zero frequency of CV events occurred. Four studies reported data on MACE, including three studies of bupropion and one study of naltrexone/bupropion ER. For composite MACE and its components, the difference in proportions between naltrexone/bupropion ER-, bupropion-, or naltrexone-treated patients compared with active comparators or placebo-treated patients did not exceed 2.5%. In conclusion, the available human evidence does not indicate an increased risk of CV events or MACE following use of naltrexone/bupropion ER, naltrexone with bupropion, or the individual components.
纳曲酮/安非他酮缓释片（ER；Contrave）是一种缓释、固定剂量的复方药物，含有纳曲酮（8毫克）和安非他酮（90毫克），用于治疗患有肥胖症或超重且至少有一种与体重相关合并症的患者。患有或未患有合并症的肥胖和超重患者心血管（CV）风险增加。鉴于该患者群体的CV风险增加，开展了这项系统性文献综述，以评估报告主要不良CV事件（MACE）和其他CV事件的人体研究。纳入标准包括2012年1月1日至2021年9月30日发表的临床研究（随机和观察性研究），其数据比较了纳曲酮/安非他酮缓释片使用者、纳曲酮与安非他酮联用者、单用安非他酮者、单用纳曲酮者与对照群体（安慰剂或其他治疗），且有足够信息按治疗组确定MACE或其他CV不良事件的发生频率。在检索到的2539篇英文文章中，70篇符合纳入标准：7项关于纳曲酮/安非他酮缓释片或纳曲酮与安非他酮联用的研究，32项关于安非他酮的研究，以及31项关于纳曲酮的研究。与未使用者相比，没有研究报告纳曲酮/安非他酮缓释片使用者、纳曲酮与安非他酮联用者、单用安非他酮者或单用纳曲酮者发生MACE的风险增加。一半的现有研究（n = 35）报告无（零）CV事件，另一半（n = 35）报告发生了非零频率的CV事件。4项研究报告了MACE数据，包括3项关于安非他酮的研究和1项关于纳曲酮/安非他酮缓释片的研究。对于复合MACE及其组成部分，与活性对照或安慰剂治疗患者相比，纳曲酮/安非他酮缓释片、安非他酮或纳曲酮治疗患者的比例差异不超过2.5%。总之，现有的人体证据未表明使用纳曲酮/安非他酮缓释片、纳曲酮与安非他酮联用或其单一成分后CV事件或MACE风险增加。
