Association between perioperative statin–ezetimibe therapy and reoperation following arthroscopic rotator cuff repair: A TriNetX database study

Background Hyperlipidemia (HLD) impairs tendon healing and is associated with increased revision risk following arthroscopic rotator cuff repair (ARCR). While statins may partially mitigate this effect, residual dyslipidemia may impair healing. Ezetimibe, through inhibition of intestinal cholesterol absorption, has demonstrated favorable effects on tendon healing in preclinical studies. Objectives This study evaluated whether perioperative statin–ezetimibe therapy is associated with improved postoperative outcomes following ARCR compared with statin monotherapy and patients without HLD. Methods A retrospective cohort study was conducted using the TriNetX Research Network. Adult patients undergoing ARCR were stratified into three cohorts based on HLD status and perioperative (± 6 months) lipid-lowering therapy: (1) documented HLD treated with statin–ezetimibe prescriptions, (2) patients without documented HLD or lipid-lowering therapy prescriptions, and (3) documented HLD treated with statin monotherapy prescriptions. Primary comparisons were predefined between cohort 1 and cohorts 2 and 3. Propensity score matching (1:1) adjusted for demographics and comorbidities. Tear size and presence of fatty atrophy and fatty infiltration were not adjusted for. Outcomes occurring within 5 years included revision rotator cuff repair (RCR), conversion to shoulder arthroplasty, and secondary shoulder arthroscopy. Results After matching, 1,066 patients were included in cohorts 1 and 2 and 1,114 patients in cohorts 1 and 3. Compared with patients without HLD, statin–ezetimibe therapy demonstrated similar rates of revision RCR (5.4% vs. 6.4%; RR 0.853; p = 0.358), conversion to shoulder arthroplasty (RR 1.227; p = 0.470), and secondary arthroscopy (RR 0.846; p = 0.260). Compared with statin monotherapy, statin–ezetimibe therapy was associated with lower rates of revision RCR (5.6% vs. 8.0%; RR 0.697; p = 0.023) and secondary shoulder arthroscopy (7.3% vs. 9.6%; RR 0.757; p = 0.048), while arthroplasty rates remained similar (RR 1.261; p = 0.400). Conclusion Among patients with HLD undergoing ARCR, perioperative statin–ezetimibe therapy was associated with lower reoperation rates compared with statin monotherapy and postoperative outcomes comparable to patients without HLD. These findings support further investigation of intensified lipid-lowering therapy, while accounting for tear size and fatty infiltration.