Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta‐analyses

Abstract

Summary Despite being approved for clinical use, evidence of cardiovascular safety (CV) is lacking for treatment with bupropion, naltrexone, or their combination (B‐N). The purpose of the study is to determine the relationship between these treatments and the risk of major cardiovascular adverse events (MACE). Phase 3 randomized clinical trials (RCT) evaluating bupropion, naltrexone, or B‐N versus control with reported incidence of MACE. The meta‐analysis included 12 RCTs, 69% for weight loss and 29% for smoking cessation, with 19,176 patients and 7354 patient‐years who were randomized to an active treatment (bupropion [n = 2965] or B‐N [n = 6980] or naltrexone [n = 249]) versus control (placebo [n = 6968] or nicotine patch [n = 2014]). The mean age was 54 ± 8 years (55% female), and the baseline BMI was 32 ± 5 kg/m2. The additive network meta‐analysis model for random effects showed no association between bupropion, B‐N, or naltrexone and MACE (odds ratio [OR] = 0.90 [95%CI 0.65–1.25], p = 0.52; OR = 0.97 [95%CI 0.75–1.24], p = 0.79; OR = 1.08 [95%CI 0.71–1.63], p = 0.73, respectively; I2 = 0%, p = 0.86). Meta‐regression analyses showed no significant association between MACE and potential confounders from RCT demographic disparities (p = 0.58). The statistical power (post hoc two‐tailed) for non‐inferiority was 91%, giving a strong probability of validity. Naltrexone, bupropion, or B‐N is not associated with the incidence of MACE as compared with placebo.

Pharmacotherapy of obesity: an update on the available medications and drugs under investigation

“… 108 The CV safety was recently evaluated in a network meta-analysis of phase 3 trials on NB, using each drug separately or in combination, for smoking cessation or for weight management, and showed no increased risk of major adverse cardiovascular events, defined as MACE. 109 …”

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

“…Sposito et al conducted a systematic literature review and meta-analysis of Phase 3 RCTs evaluating bupropion, naltrexone, or naltrexone with bupropion, and found no significant difference in the incidence of MACE between treatment groups. 87 …”

“…Sposito et al conducted a systematic literature review and meta-analysis of Phase 3 RCTs evaluating bupropion, naltrexone, or naltrexone with bupropion, and found no significant difference in the incidence of MACE between treatment groups. 87 Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2022: Finally, only published articles identified in accordance with the literature search protocol were included in this review. Despite extensive efforts to identify all relevant sources available through a pre-defined search strategy, with input from experts in both the product literature and systematic literature reviews, some sources with relevant information may have been overlooked or not identified for inclusion.…”

Pharmacotherapy for obesity: moving towards efficacy improvement

“…The most frequent adverse events reported in the RCTs with NB treatment were nausea, headache, and constipation [ 66 , 67 ]. Cardiovascular safety still needs to be investigated by a RCT, but a recent systematic review and meta-analysis found no association between the use of naltrexone, bupropion, or their combination and the incidence of major cardiovascular adverse events compared with placebo [ 70 ]. Nevertheless, patients with hypertension or other cardiovascular diseases should be aware of the small but not trivial sympathomimetic effects of bupropion, as it can increase blood pressure and heart rate [ 65 ].…”