Effect of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers on need for operative intervention for idiopathic adhesive capsulitis

BACKGROUND: The exact pathogenesis of idiopathic adhesive capsulitis (IAC) is not fully understood, but an inflammatory profibrotic cascade, largely mediated by transforming growth factor-beta 1 (TGF- β1) has been implicated. Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACE-Is) both decrease the activity of TGF-β1. The aim of this study was to determine the impact of ACE-Is or ARBs use on the need for operative intervention in IAC. METHODS: This was a retrospective cohort study of patients from a single institutional database with IAC, divided into two cohorts, with and without ACE-I and/or ARB use as the primary exposure and a minimum 2-year follow-up. The primary outcome measured was the incidence of operative intervention including manipulation under anesthesia (MUA) and arthroscopic capsular release (ACR). Additional multivariable logistic regression analysis was performed to evaluate associations between ACE-I/ARB use and likelihood of undergoing an operative procedure. RESULTS: A total of 17,645 patients met inclusion criteria, with 5424 patients in the ACE-I/ARB cohort and 12,221 in the non-ACE-I/ARB cohort. Overall, 422 (2.4%) patients underwent surgical treatment, 378 (2.1%) ACR, and 74 (0.4%) MUA. There was no significant difference between cohorts in the frequency of surgical procedures or time to procedure since diagnosis. There were no significant differences between individual ACE-Is or ARBs, although Losartan was found to have a trend of decreased rate of intervention (31.7% vs. 36.8%, P = .209) when compared to patients not on losartan that did not reach statistical significance. Patient factors predictive of undergoing MUA/ACR were diabetes (P = .013), obesity (P < .001), and male sex (P < .001). Increasing patient age reduces the likelihood of undergoing operative intervention, with patients aged 50-70 years (P = .022) and age >70 years (P < .001) demonstrating reduced odds as compared to patients aged <30 years. CONCLUSION: Patients with IAC have an overall low (2.4%) rate of requiring surgical intervention. While the antifibrotic mechanism of ACE inhibitors and ARBs did not significantly affect the rate of requiring surgical intervention, male gender, obesity, younger age, and diabetes, all increased the risk for operative intervention. Losartan, specifically, may have a disease modifying effect on IAC that should be investigated with larger controlled trials.