# Cardiovascular safety of fixed-dose extended-release naltrexone/bupropion in clinical practice

## TL;DR

This study found that a drug combination for weight loss does not increase heart-related risks compared to another drug.

## Contribution

The study provides real-world cardiovascular safety data for naltrexone/bupropion in routine clinical practice.

## Key findings

- Patients on NB-ER had similar rates of major adverse cardiovascular events compared to those on lorcaserin.
- No deaths occurred within 30 days of a heart attack or stroke in the NB-ER group.
- NB-ER was not associated with increased nonfatal stroke or heart attack rates.

## Abstract

The fixed-dose extended-release combination of naltrexone/bupropion (NB-ER) is indicated to treat overweight and obesity in adults as an adjunct to a reduced-calorie diet and increased physical activity. This study compared the rate of major adverse cardiovascular events (MACE) and its components (nonfatal acute myocardial infarction [AMI], nonfatal stroke, and cardiovascular death) between patients initiating NB-ER and those initiating lorcaserin (removed from US market in 2020; included as active comparator to minimize possible confounding by indication) in routine clinical practice.

This was a retrospective cohort study with a new-user, active-comparator design. Patients initiating NB-ER or lorcaserin were identified using Arcadia Data Research electronic health records, including insurance claims (June 2012–February 2020). Incidence rate ratios were estimated, and adjusted hazard ratios (aHRs) with 95 % confidence intervals (CIs) were estimated using a propensity score (PS)-weighted Cox proportional hazard model in an intention-to-treat analysis.

Patients initiating NB-ER (n = 12 475) or lorcaserin (n = 12 171) were followed for a mean observation period of 4.7 years. After PS weighting, baseline comorbidities, concomitant medications, lifestyle factors, and clinical measures were balanced between cohorts. MACE incidence was 0.77/1000 person-years for NB-ER and 1.03/1000 person-years for lorcaserin. Compared to lorcaserin, patients initiating NB-ER had statistically similar rates of MACE (aHR, 0.76; 95 % CI, 0.48–1.22), nonfatal AMI (aHR, 0.74; 95 % CI, 0.45–1.23), and nonfatal stroke (aHR, 1.05; 95 % CI, 0.34–3.22). No deaths were observed within 30 days of an AMI or stroke.

Patients initiating NB-ER compared with lorcaserin were not at an increased risk of MACE or its components. Conclusions from this study must be interpreted in the context of certain assumptions related to PS methodology and use of lorcaserin as an active comparator. Causal interpretations for the cardiovascular safety of NB-ER should be evaluated further in a prospective, randomized, blinded, controlled clinical trial.

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•EHR data showed fixed-dose extended-release naltrexone/bupropion (NB-ER) vs lorcaserin did not have increased CV events.•Patients initiating NB-ER vs lorcaserin did not experience increased rates of nonfatal stroke or nonfatal AMI.•No deaths were observed within 30 days of an AMI or stroke event among patients initiating NB-ER.

EHR data showed fixed-dose extended-release naltrexone/bupropion (NB-ER) vs lorcaserin did not have increased CV events.

Patients initiating NB-ER vs lorcaserin did not experience increased rates of nonfatal stroke or nonfatal AMI.

No deaths were observed within 30 days of an AMI or stroke event among patients initiating NB-ER.