The Role of Systemic Antifibrotic Agents on Patient and Surgical Outcomes After Joint Surgery: A Systematic Review.

Postoperative arthrofibrosis (PTAF) is a debilitating complication of orthopaedic surgery, causing pain, stiffness, and reduced quality of life. Antifibrotic agents (statins, angiotensin receptor blockers [ARBs], and angiotensin-converting enzyme inhibitors [ACEIs]) have been proposed to mitigate PTAF, yet no systematic review has evaluated all three across major orthopaedic surgeries. This review synthesizes evidence on their use for preventing PTAF after shoulder, knee, and hip surgery. PubMed, Google Scholar, and Scopus were searched for clinical studies evaluating statins, ARBs, or ACEIs for PTAF outcomes with ≥90-day follow-up. Quality was assessed using MINORS and ROBINS-I. Fourteen observational studies met (12 retrospective cohort and 2 case-control) inclusion. Most studies investigated ARBs (12 studies), with fewer studies investigating ACEIs (7) and statins (5). The mean MINORS score was 17.6, and most (10/14) had serious risk of bias. In total knee arthroplasty (TKA), three studies linked ARBs to reduced manipulation under anesthesia (MUA) or lysis of adhesions, although four found no effect on MUA, range of motion (ROM), or arthrofibrosis. ACEI results were inconsistent, with one study showing modestly reduced MUA but three others no effect; ROM findings were mixed, including one reporting worse outcomes. Statins showed no benefit, and pooled TKA/total hip arthroplasty data found no drug associations with MUA. In arthroscopic rotator-cuff repairs (ARCRs), ARBs were associated with reduced adhesive capsulitis and improved ROM inconsistently. ACEI use correlated with worse ROM and patient-reported outcomes, while statins again showed no effect. A pooled analysis of arthroscopic shoulder procedures reported no associations between ARBs or ACEIs and PTAF outcomes. Current observational data provide conflicting and insufficient support for using statins, ARBs, or ACEIs to prevent PTAF. While some studies suggest a potential benefit for ARBs in TKA and ARCR, findings are inconsistent. Higher quality studies are needed to better understand their clinical role in preventing PTAF.