Suzetrigine Use After Breast Reconstruction Surgery and Postoperative Outcomes: A Propensity Score–Matched Retrospective Cohort Study

This study is a retrospective, propensity score–matched cohort analysis of secondary electronic health record data from the TriNetX Global Collaborative Network, a federated network of de-identified EHR data from 180 participating healthcare organizations. The purpose of this study is to evaluate whether perioperative use of suzetrigine — a first-in-class, non-opioid, selective NaV1.8 pain-signal inhibitor approved by the FDA in January 2025 for moderate-to-severe acute pain — is associated with differences in postoperative outcomes among women undergoing breast reconstruction (implant-based, expander-based, or autologous). Two cohorts of women aged ≥18 years who underwent a qualifying breast reconstruction procedure will be identified: an exposed cohort with at least one instance of suzetrigine use within 7 days on or after the index procedure, and a comparator cohort with no suzetrigine use within 6 months on or after the index procedure. Cohorts will be balanced using 1:1 nearest-neighbor propensity score matching on demographic and clinical covariates (including age, race, ethnicity, and prespecified psychiatric, pain-related, and medical comorbidities, plus receipt of chemotherapy or radiation). Six postoperative outcomes, assessed in the 8–90-day window after the index procedure, will be evaluated: (1) opioid use, (2) emergency department visits, (3) postoperative nausea/vomiting, (4) hospital admission, (5) antiemetic use, and (6) naloxone administration. For each outcome, risk analyses (risk difference, risk ratio, odds ratio), Kaplan-Meier survival analyses with Cox proportional-hazards modeling, and number-of-instances analyses will be performed on the matched cohorts. We hypothesize that perioperative suzetrigine use will be associated with reduced downstream opioid use and opioid-related morbidity in the 90 days following breast reconstruction. Because this is a retrospective analysis of routinely collected, de-identified, aggregated EHR data (no patient-level data are accessed by the research team), this registration documents the a priori analytic plan for a secondary data study in accordance with STROBE and RECORD reporting guidance, in order to promote transparency and distinguish confirmatory from exploratory findings.