The TICTAC trial was well done and had some important findings. Unfortunately, it was not a clinical trial of steroid discontinuation because there was no group of patients kept on steroids.
Also, when compared with patients in a similar trial who were given tacrolimus-MMF (Am. J. Transplant. 2006;6:1377-86), patients in the TICTAC trial had higher levels of tacrolimus and serum creatinine. These differences are a little worrisome in terms of long-term outcomes.
At my institution, even later withdrawal of steroids (that is, among patients who were on steroids for at least 4 years without any acute rejection episodes) was associated with a 25% incidence of acute rejection (Transplant Proc. 2007;39:2372-4). In Spain, centers typically stop steroids only in patients who have unacceptable adverse effects and a low immunologic risk for rejection.
Only one trial has directly compared early steroid withdrawal with standard steroid therapy in transplant recipients (Am. J. Transplant. 2008;8:307-16). In that study, in kidney transplant patients who either did not receive any steroids or received them for just the first week, acute rejection occurred both earlier and more often than in the standard therapy group. And there were only modest reductions in adverse events.
In heart transplantation, immunosuppressive therapy is not a one-size-fits-all undertaking. Some patients (for example, those who have preexisting osteoporosis, are elderly, or have diabetes) do benefit from early withdrawal of steroids.
Indeed, guidelines recommend steroid weaning in patients who experience significant adverse effects and have not had a recent acute rejection episode (J. Heart Transplant. 2010;29:914-56). But they also note that although several studies have shown that it is feasible and safe to wean most patients by 6-12 months, and that doing so is desirable to reduce adverse effects, there has not been a randomized trial testing this practice.
It is possible that future well-designed studies will show that the risk of rejection is a reasonable price to pay for avoiding the adverse effects of steroids. These studies must have long-term follow-up and assess the key outcomes of graft and patient survival, rather than just rejection.
In conclusion, there are certainly patients who benefit from early withdrawal of steroids, but current evidence does not support the generalization of this practice.
Dr. Crespo-Leiro is with the heart failure and heart transplant unit at the Hospital Universitario a Coruña (Spain).