School of Medicine, Royal College of Surgeons in Ireland - Bahrain, Bahrain.
Department of Pharmacy Services, Cleveland Clinic Abu Dhabi, Al Maryah Island, Abu Dhabi, United Arab Emirates; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, United States of America.
Prog Cardiovasc Dis. 2020 May-Jun;63(3):194-209. doi: 10.1016/j.pcad.2020.03.007. Epub 2020 Mar 20.
Cardiac allograft vasculopathy (CAV)-mediated by a heterogeneous myriad of immune and non-immune factors, which contribute to the progressive and diffuse thickening of the arterial allograft's tunica intima in one distinct form of CAV, and the build-up of plaque in another-is a major limiting factor of long-term survival post heart transplantation. Information on the optimal pharmacotherapeutic approaches for the prevention and management of CAV is conflicting, scattered, and inconsistent, with numerous recent studies adding to the literature. In this paper, we present a go-to clinical resource with the most updated and comprehensive information on the topic. Immunosuppressant therapy remains a staple, with mTOR inhibitors and mycophenolate mofetil (MMF) showing direct correlation with CAV prevention. More data is now available with calcineurin inhibitor (CNI) minimizing or sparing regimens. More novel approaches are being investigated for the roles of monoclonal antibodies, anti-thymocyte globulin, and bortezomib in preventing or delaying CAV. On the other hand, statins' established efficacy is attributed to lipid-lowering and lipid-independent immunomodulatory effects, with early initiation associated with improved outcomes. The choice of statin is dependent on drug-drug interactions. Other aiding approaches for the prevention of CAV include antioxidant vitamins, aspirin, vasodilators, folate therapy, and, most pertinently, cytomegalovirus prophylaxis. Larger clinical trials are needed before these options are institutionalised. For management of established CAV, early initiation of augmented immunosuppressive therapies may be effective, as well as CNI conversion to mTOR inhibitors with or without standard MMF and azathioprine therapy. Risk of acute rejection needs to be monitored during conversion. Finally, preclinical investigations highlight novel potential therapies for CAV prevention and attenuation, however robust clinical trials are needed to test their efficacy and safety.
心脏同种异体移植物血管病（CAV）由多种免疫和非免疫因素介导，这些因素导致动脉同种异体移植物的内膜进行性和弥漫性增厚，形成 CAV 的一种独特形式，另一种形式则是斑块的形成，这是心脏移植后长期存活的主要限制因素。关于预防和管理 CAV 的最佳药物治疗方法的信息存在冲突、分散且不一致，最近有许多研究对此进行了补充。在本文中，我们提供了一个临床资源，其中包含了关于该主题的最新和最全面的信息。免疫抑制剂治疗仍然是主要方法，mTOR 抑制剂和霉酚酸酯（MMF）显示与 CAV 预防直接相关。现在有更多的数据表明钙调磷酸酶抑制剂（CNI）最小化或豁免方案。更多的新方法正在研究单克隆抗体、抗胸腺细胞球蛋白和硼替佐米在预防或延迟 CAV 中的作用。另一方面，他汀类药物的疗效归因于降脂和非依赖性免疫调节作用，早期开始使用与改善结果相关。他汀类药物的选择取决于药物相互作用。预防 CAV 的其他辅助方法包括抗氧化维生素、阿司匹林、血管扩张剂、叶酸治疗，以及最重要的是巨细胞病毒预防。在这些方法得到制度化之前，需要进行更大规模的临床试验。对于已确诊的 CAV 的治疗，早期开始增强免疫抑制治疗可能有效，还可以将 CNI 转换为 mTOR 抑制剂，同时或不使用标准的 MMF 和硫唑嘌呤治疗。在转换过程中需要监测急性排斥反应的风险。最后，临床前研究强调了预防和减轻 CAV 的新潜在疗法，但需要进行强有力的临床试验来测试其疗效和安全性。
