Delayed Onset of Cardiac Allograft Vasculopathy by Induction Therapy Using Anti-thymocyte Globulin Ruoyu Zhang, MD, Axel Haverich, MD, PhD, Martin Strüber, MD, PhD, Andre Simon, MD, PhD, and Christoph Bara, MD Background: In this study we sought to compare the long-term effects of anti-thymocyte globulin (ATG) and muromonab-CD3 (OKT3) as induction therapy after heart transplantation, with special regard to cardiac allograft vasculopathy (CAV), post-transplant infections, post-transplant non-skin cancers and patient survival. Methods: From 1988 to 1991, 25 heart transplant patients received OKT3 as induction treatment. Accordingly, 25 consecutive patients who received ATG and 25 consecutive patients without induction therapy were enrolled. Results: At a follow-up period of 13.4  4.6 years, time to onset of non-significant and significant CAV was 8.77  3.38 and 11.60  4.28 years, respectively, in the ATG group, which was significantly delayed compared with 5.71  3.08 and 7.44  2.74 years, respectively, in the non-induction group. In the OKT3 group, time to onset of non-significant and significant CAV (6.10  2.73 and 7.86  3.19 years, respectively) did not differ significantly from the non-induction group. Ten- and 15-year actuarial survival rates of ATG- and OKT3-treated patients were not significantly different from those of patients without induction treatment. Conclusions: Our study suggests the long-term advantage of ATG in prevention of cardiac allograft vasculopathy. In contrast, OKT3 failed to show such benefit. However, induction therapy with either ATG or OKT3 did not exhibit a significant beneficial effect on long-term patient survival. J Heart Lung Transplant 2008;27:603–9. Copyright © 2008 by the International Society for Heart and Lung Transplantation. Despite improvement in early outcome of heart trans- plantation (HTx), chronic rejection in the form of cardiac allograft vasculopathy (CAV) continues to limit long-term graft and patient survival. 1,2 Aggressive pro- gression of CAV was associated with poor long-term outcome of HTx. Luyt et al found that approximately 50% of patients with moderate coronary lesions had disease progression to a critical lesion or occlusion over a 1-year period. 3 Furthermore, a retrospective multi- center study involving 2,609 HTx patients demon- strated that the likelihood of progression to severe CAV was increased from 9% to 19% within 5 years, once mild CAV was identified angiographically. 4 The mechanisms of chronic rejection have not been clearly elucidated. 4–6 However, some studies have dem- onstrated that frequency and severity of acute rejec- tions are associated with the subsequent development of chronic rejection in adult recipients. 7–10 Anti-thymo- cyte globulin (ATG) and muromonab-CD3 (OKT3) are commonly used forms of induction treatment after HTx, which can decrease acute rejections and achieve greater short-term graft and patient survival. 11–13 How- ever, it is still not clearly established whether induction therapy with ATG or OKT3 can also reduce the inci- dence of chronic rejection in CAV. According to Carrier et al, ATG-treated HTx recipients had a lower incidence of CAV during a follow-up period of 10 years, but their findings were not statistically significant. 14 Moreover, the short-term benefits of induction therapy are associ- ated with a potentially increased risk of post-transplan- tation malignancy and infections. It has not been well elucidated whether ATG and OKT3 as induction treat- ment following cardiac transplantation can improve the long-term survival of HTx recipients. This study aimed to detect long-term clinical benefits of ATG and OKT3 as immunosuppressive induction regimens over non-induction therapy, with special re- gard to acute rejections, cardiac allograft vasculopathy, From the Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. Submitted August 26, 2007; revised December 30, 2007; accepted February 17, 2008. Reprint requests: Ruoyu Zhang, MD, Department of Cardiac, Tho- racic, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. Tele- phone: +49-511-532-6582. Fax: +49-511-532-5404. E-mail: zhang. ruoyu@mh-hannover.de Copyright © 2008 by the International Society for Heart and Lung Transplantation. 1053-2498/08/$–see front matter. doi:10.1016/ j.healun.2008.02.016 603 ALLOGRAFT VASCULOPATHY