EFFECTS OF METHOTREXATE ON ACUTE REJECTION AND CARDIAC ALLOGRAFT VASCULOPATHY IN HEART-TRANSPLANT RECIPIENTS

Background: In heart transplant recipients methotrexate has been shown to reverse recurrent/persistent acute rejection refractory to intensi fied conventional immunosuppression. This study sought to determine wh ether methotrexate produces a sustained decline of heart allograft rej ection rates and renders rejection rates of patients with a history of recurrent/persistent rejection similar to those of heart transplant r ecipients without such history. Methods: Rejection, infection, and car diac allograft vasculopathy were compared in 35 patients treated with methotrexate (12 +/- 9 mg/week for 34 +/- 54 weeks) and 236 patients n ever given methotrexate. Because the mean time from transplantation to initiation of methotrexate was 9.4 months, patients treated without m ethotrexate were analyzed for events less than or equal to 9.4 versus > 9.4 months after heart transplantation. Results: Demographics, perio perative and maintenance immunosuppression, and postoperative follow-u p time (58 +/- 32 vs 57 +/- 33 months) were similar in the two groups. Rejection rates decreased in both groups but remained significantly h igher in the patients treated with methotrexate after initiation of th erapy than in the patients treated without methotrexate more than 9.4 months after transplantation (0.15 +/- 0.16 vs 0.06 +/- 0.12 episodes/ patient/month; p = 0.0014). Infection rates were higher in patients af ter methotrexate initiation than in patients treated without methotrex ate more than 9.4 months after heart transplantation (0.17 +/- 0.24 vs 0.06 +/- 0.13 episodes/patient/month; p = 0.015). At the end of the f ollow-up period methotrexate- and non-methotrexate-treated groups did not differ in the percentage of patients with angiographically detecta ble cardiac allograft vasculopathy (17.1% and 21.2%, respectively) and survival (71.4% and 64.0%, respectively). Conclusions: Even after rev ersal of rejection by methotrexate, patients requiring methotrexate fo r the treatment of persistent/recurrent rejection continued to have hi gher rejection rates than patients not requiring methotrexate. In spir e of persistently higher rejection rates, patients treated with methot rexate did not have higher rates of cardiac allograft vasculopathy. Th is finding raises the question whether methotrexate provides a protect ive influence on the development of cardiac allograft vasculopathy in this high-risk group.