Use of Contrave, Naltrexone with Bupropion, Bupropion, or Naltrexone and Major Adverse Cardiovascular Events: A Systematic Literature Review

Abstract

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. A priori 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.

Keywords:

• MACE
• obese
• overweight
• cardiovascular risk

Acknowledgments

We would like to thank the following individuals for their assistance with data abstraction and quality control: Ms. Maribeth Anderson, Dr. Benjamin Davis, Dr. Anam Khan, Dr. Anais Kahve, Ms. Callan Krevanko, Dr. Ryan Lewis, Dr. Jowanna Malone, and Dr. Nnaemeka Odo. Additionally, we would like to thank Ms. Hope Mueller and Dr. Michael Kyle for their review of this manuscript.

Disclosure

SD, ETC, SRW, PD are employees and ETC and SRW are stockholders of Exponent, a multidisciplinary science and engineering consultancy. MER is a consultant and EG is an employee of Currax Pharmaceuticals, LLC, a specialty pharmaceutical business focused on acquiring and commercializing prescription drugs within the US market. Currax Pharmaceuticals owns the world-wide rights to Contrave. The authors report no other conflicts of interest in this work.

Additional information

Funding

This work was funded by a research contract between Currax Pharmaceuticals, LLC, and Exponent, Inc., that provided Exponent with the right to publish findings of all research projects commissioned.