Rapid Weaning of Steroids after Cardiac Transplantation Improves Outcomes

Abstract

Modern regimen using corticosteroids (CS), tacrolimus and MMF reduced acute rejection rates after heart transplantation (HTx), but has not translated into improved long-term outcomes, potentially due to the complications of the drugs themselves. Therefore, many centers have tried to avoid or minimize CS, and in 2010 we adopted a weaning protocol, changing from a high dose CS regimen (1 mg/kg/day declining in the first month), to a low dose approach (prednisone 20 mg daily on day 3 with weaning within 9 months). All patients received induction with RATG and methylprednisolone. Our primary endpoint was a combination of 1) Freedom from allograft rejection, ISHLT ≥ 2R; and 2) Freedom for infections or CAV. We also measured mortality and the rate of post-transplant diabetes (PTDM). Patients who underwent HTx at our center were divided according to the era of HTx: Early (Ea): 1983 to 1998; recent (Re) 1999 to 02/2010 and latest (Le) eras: 03/2010 - 06/2018. 418 patients were followed (Ea: 197; Re: 133; Lt: 88). Mean dose of CS were 30.1±9.3, 12.5±6.3 (Ea:); 28.±9.9, 6.32±3.2 (Re:); and 19.2±2.2, 5.3±3.4 (Le) at discharge and 6 months respectively. Compared to Lt, earlier cohorts had higher risk for primary endpoint (figure), for infection (HR: 2.01; 95% CI: 1.46-2.76; HR: 2.37; 95%CI: 1.70-3.30, for Ea and Re respectively) and rejection rates (Ea: HR: 2.66; 95% CI: 1.98-3.58; Re: HR: 43.12; 95% CI: 5.98-310.7), all p < 0.001. The presence of CAV and mortality were higher in Ea (HR: 4.13; 95% CI: 1.8 to 9.5 and HR: 3.50; 95% CI: 2.09-5.85, both p<0.0001 but similar between Re vs Le (p=NS). Surprisingly, the rate of PTDM diabetes remained unchanged 1 and 3 years after HTx between eras (p=0.25). The adoption of a low-dose and rapid CS weaning after HTx improves long-term outcomes by reducing infection and rejection rates, but not new onset diabetes or mortality. Our observations on CS minimization, if confirmed by others, have the potential of reducing the multiple morbidities associated with long-term CS use.