Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients

BACKGROUND Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vascutopathy (CAV) after heart transplantation (HT). However, data on the tong-term effect on CAV progression and clinical outcomes are tacking. OBJECTIVES The aim of this study was to test the tong-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT. METHODS A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascutar ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies. RESULTS The progression in plaque volume (2.8 +/- 2.3 mm(3)/ mm vs. 0.46 +/- 1.8 mm(3)/mm; p < 0.0001) and plaque index (plaque volume-to-vessel volume ratio) (12.2 +/- 9.6% vs. 1.1 +/- 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CM. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was tower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p < 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (<= 2 years) compared with tate conversion (>2 years) after HT. CONCLUSIONS Early conversion to SRL is associated with attenuated CAV progression and with tower long-term mortality and fewer CAV-related events compared with continued CNI use. (C) 2018 by the American College of Cardiology Foundation.