History of Preoperative Use of Gabapentin Before Lower Extremity Bypass Predisposes Patients to a High Risk of Opioid Use and Dependence in a Dose-Dependent Manner

Patients suffering from peripheral artery disease are commonly prescribed gabapentinoids (GBPs; gabapentin and pregabalin) for pain management. In this study, we investigate the impact of preoperative use of GBPs on postoperative risk of opioid-related disorders in patients with peripheral artery disease undergoing lower extremity bypass operation. This is a retrospective propensity-score-matched analysis of patients undergoing peripheral artery bypass in TriNetX, a multicenter population-level database. Two study groups were constituted based on the preoperative history of prescribed GBPs. Patients with a history of opioid-related disorders before lower extremity bypass were excluded from the study. The patient population was matched using propensity score matching to balance the groups on potential confounders. Primary outcomes were opioid-related disorders and mortality. The outcomes were reported at two time end points (1 and 5 years), and effect estimates were reported in adjusted odd ratios (OR) and 95% confidence intervals (CIs), Bonferroni-adjusted P values were calculated, and significance was set at a P value of <.05. This study population included a total of 23,706 patients. After propensity score matching, the study population included 10,260 patients. Each of the two groups contained 5130 patients with a mean (standard deviation) age of 66.4 (9.7) years in the no GBPs group vs 66.5 (9.3) years in the GBPs group. Primary outcomes showed a significant increase in postoperative opioid- related disorders at the 1- and 5-year time points between the GBPs and no GBPs groups: 1-year outcome (2.0% vs 1.1%; adjusted P = .007) and 5-year outcome (4.5% vs 3.5%; adjusted P < .035). Logistic regression analysis revealed a statistically significant increase in the 1-year (adjusted OR = 1.664; 95% CI [1.217, 2.273], P = .001) and 5-year (OR = 1.353; 95% CI [1.107, 1.653], P = .003) odds of opioid-related disorders in patients with a preoperative history of GBPs. Secondary χ2 analysis showed a significant dose-dependent increase in the risk of 5-year opioid-related disorders in patients with a history of prescribed gabapentin (P < .001): low dose (<800 mg/d) (2.6%), medium dose (800-1600 mg/d) (5.8%), and high dose (>1600 mg/d) (6.1%). In patients undergoing lower extremity bypass with a history of gabapentin use, there is an associated increased long-term risk of opioid-related disorders in a dose-dependent manner. Overall, this study highlights the importance of understanding, evaluating, and further investigating the risk-to-benefit ratio of prescribing GBPs for pain control vs their long-term risk of opioid-related disorders among other adverse outcomes.