Anzillotti Giuseppe, Gomoll Andreas H, Conte Pietro, Bulgarelli Alberto, Queirazza Paolo, Marcacci Maurilio, Kon Elizaveta, Di Matteo Berardo
IRCCS Humanitas Research Hospital Rozzano Milan Italy.
Department of Biomedical Sciences Humanitas University Pieve Emanuele Milan Italy.
J Exp Orthop. 2024 Dec 11;11(4):e70089. doi: 10.1002/jeo2.70089. eCollection 2024 Oct.
Despite advances in surgical techniques and rehabilitation protocols, arthrofibrosis following total knee arthroplasty (TKA) still has poor outcomes. In the last decade, attention has been focused on the pathogenesis and cascade of events leading to the development of fibrosis. Currently, one of the most promising approaches consists in the indirect antagonisation of transforming growth factor beta 1 () through the downregulation of the renin-angiotensin-aldosterone system (RAAS). This systematic review aims to analyse the available evidence regarding the use of angiotensin receptor blockers (ARBs)/angiotensin-converting-enzyme inhibitors (ACEi) in order to prevent post-operative knee arthrofibrosis following TKA.
Extensive research on the PubMed, Cochrane, and Google Scholar databases was performed on 8 July 2024, using keywords related to ARBs, ACE inhibitors and arthrofibrosis. Inclusion criteria included: (1) clinical trials of any level of evidence; (2) written in English; (3) studies conducted on humans; and (4) evaluating the antifibrotic effects of ACE inhibitors or ARBs administered for TKA surgeries. Exclusion criteria were articles written in other languages; preclinical studies; expert opinions; reviews and trials evaluating the effects of ACEi/ARBs not related to their antifibrotic effect after TKA.
A total of six studies met the inclusion criteria and were analysed. All studies were retrospective and involved a total of 158,310 patients. Time of administration varied among the studies as well as the dosage, which fell within the range for cardiological use. Four out of six studies focused exclusively on losartan. Three studies reported a clear, significant correlation between the use of ARBs and/or ACEi and a reduced likelihood of developing arthrofibrosis.
The RAAS antagonism could have potential for stiffness prevention after TKA. However, given the side effects and the limited evidence available, the use of ACEi/sartans for the sole purpose of avoiding arthrofibrosis after TKA is not currently recommended.
Level III.
尽管手术技术和康复方案取得了进展，但全膝关节置换术（TKA）后的关节纤维化结局仍较差。在过去十年中，注意力集中在导致纤维化发展的发病机制和一系列事件上。目前，最有前景的方法之一是通过下调肾素-血管紧张素-醛固酮系统（RAAS）间接拮抗转化生长因子β1（）。本系统评价旨在分析关于使用血管紧张素受体阻滞剂（ARBs）/血管紧张素转换酶抑制剂（ACEi）预防TKA术后膝关节纤维化的现有证据。
2024年7月8日，在PubMed、Cochrane和谷歌学术数据库上进行了广泛研究，使用了与ARBs、ACE抑制剂和关节纤维化相关的关键词。纳入标准包括：（1）任何证据水平的临床试验；（2）用英文撰写；（3）在人类身上进行的研究；（4）评估用于TKA手术的ACE抑制剂或ARBs的抗纤维化作用。排除标准为用其他语言撰写的文章；临床前研究；专家意见；评估ACEi/ARBs与TKA后抗纤维化作用无关的作用的综述和试验。
共有六项研究符合纳入标准并进行了分析。所有研究均为回顾性研究，共涉及158310名患者。给药时间和剂量在研究中各不相同，剂量在心脏病学使用范围内。六项研究中有四项专门关注氯沙坦。三项研究报告称，使用ARBs和/或ACEi与关节纤维化发生可能性降低之间存在明确、显著的相关性。
RAAS拮抗可能对TKA后预防僵硬具有潜力。然而，鉴于副作用和现有证据有限，目前不建议仅为避免TKA后关节纤维化而使用ACEi/沙坦类药物。
三级。
