Drug-Gene Interactions Increase Risk of Adverse Outcomes Among Veterans Who Have Vascular Surgery
BACKGROUND:
Pharmacogenetics (PGx) can improve medication-related outcomes by considering a patient's DNA profile to optimize medication efficacy and minimize adverse effects. It is unknown whether drug-gene interactions (DGIs) at the time of surgery result in adverse outcomes in the postoperative setting. This retrospective study aimed to determine the association of DGIs with postsurgical outcomes among 10,098 VA hospital patients (mean age 69 years, 16% Black, 98% male) who were enrolled in the Million Veteran Program and received drugs impacted by pharmacogenetic variants 30 days prior to and up to 7 days following vascular surgery from January 1, 2011, to December 31, 2022. The study's main outcomes and measures included postsurgical length of stay (LOS), 30-day readmission, the composite of myocardial infarction, stroke, and myocardial injury after noncardiac surgery, and 30-day postoperative death.
FINDINGS:
- Veterans with DGIs at the time of vascular surgery had a longer LOS, a higher rate of 30-day readmissions, and an increased risk of cardiovascular morbidity. DGIs were not associated with 30-day mortality.
- The most common DGIs involved proton pump inhibitors (often used to treat stomach acid problems) and medications related to cardiovascular disease (e.g., beta blockers, statins).
- Most Veterans (96%) had at least 1 actionable PGx phenotype, and nearly 50% had a DGI at the time of the vascular surgery procedure.
IMPLICATIONS:
- The vascular surgery population represents an important population that may benefit from preoperative PGx testing.
- Further work is needed to determine which DGIs contribute to adverse outcomes and whether preoperative pharmacogenetic testing has the potential to mitigate these risks.
LIMITATIONS:
- As the cohort consisted primarily of male participants, results require replication in a cohort more balanced by sex.
- The investigators were limited in power to detect the clinical impact of individual medications and to detect an impact on mortality given the low rate (1%).
AUTHOR/FUNDING INFORMATION:
This study was funded by HSR (PPO 22-191), using data from the Million Veteran Program. Dr. Itani and Mr. O’Brien are with HSR’s Center for Health Optimization and Implementation Research (CHOIR). Drs. Ferraro, Teerlink, Lynch, and DuVall and Mr. O’Brien are with VA Informatics and Computing Infrastructure (VINCI). Dr. Barrett is with HSR’s Center to Improve Veteran Involvement in Care (CIVIC).
Tuteja S, O’Brien WJ, Ferraro JP, Damrauer SM, Itani KMF, Voight BF, Teerlink CC, Lynch JA, DuVall SL, Strebel T, Kim MJ, Wilson MA, Barrett TW. Drug-Gene Interactions and Clinical Outcomes After Vascular Surgery in the Million Veteran Program. JAMA Surgery. June 4, 2025;online ahead of print.
