Initiation of Gabapentin with Opioids and Risk of Respiratory Cardiovascular and Opioid‐Related Adverse Events Following Surgery for Breast Cancer

Pain is a key determinant of quality‐of‐life following breast cancer surgery, the most common cancer operation in the United States. Gabapentinoids are frequently prescribed for pain management, yet their respiratory, cardiovascular, and opioid‐related adverse effects remain unclear. This target trial emulation, analyzing US commercial claims (2013–2023), evaluated these safety outcomes under gabapentin–opioids initiation vs. opioids only during the first postoperative month following breast cancer surgery, with sustained 1‐year follow‐up. Women with nonmetastatic breast cancer were eligible on surgery dates if they had no prior outcomes, nor gabapentinoids or opioid prescriptions. Outcomes included time‐to‐first respiratory complications, major adverse cardiovascular events (MACE), arrhythmia, and high‐dose opioid utilization (≥ 50 or ≥ 90 morphine ‐milligram equivalent [MME]). We estimated 1‐year outcome risks and 95% CIs under gabapentin–opioids and opioids‐only strategies using weighted pooled logistic regressions with bootstrapping, including stabilized inverse probability weighting to adjust for baseline and time‐varying confounders. Of 86,290 eligible individuals, 1709 initiated gabapentin and opioids, and 39,372 initiated opioids only. Risks of respiratory complications (RR 1.24, 95% CI: 0.26–3.02), MACE (RR 0.95, 95% CI: 0.31–1.85), and arrhythmia (RR 0.65, 95% CI: 0.24–1.33) were comparable under gabapentin–opioids and opioids‐only. Risk of receiving opioid dosage ≥ 50 MME (RR 1.23, 95% CI: 0.85–1.72) and ≥ 90 MME (RR 1.09, 95% CI: 0.43–2.23) were comparable. This study challenged the limited evidence regarding safety concerns of adding gabapentin for pain management, finding that gabapentin–opioids initiation carried comparable respiratory and cardiovascular risks to opioids only following breast cancer surgery. However, we did not find evidence that adjunctive gabapentin reduces subsequent high‐dose opioid utilization.