ORAl iMmunosuppressive therapy to prevent in-Stent rEstenosiS (RAMSES) cooperation: a patient-level meta-analysis of randomized trials

Aims: The role of oral immunosuppressive therapy (OIT) after percutaneous coronary intervention (PCI) and stenting still remains to be defined. We sought to evaluate the efficacy and safety of oral administration of sirolimus or prednisone to prevent in-stent restenosis. Methods: We undertook a meta-analysis of trials in which PCI-patients were randomly assigned to OIT or control therapy. The primary endpoint was the composite of death/myocardial infarction (MI) or target lesion revascularization (TLR). Secondary endpoints were the composite of death/MI, the individual components of the primary endpoint and in-stent late lumen loss (LLL) at angiographic surveillance. Results: We obtained individual data of seven trials enrolling 1,246 patients (OIT, n= 608 versus control therapy, n= 638) with 1,456 coronary lesions. Median follow-up was 360 days [interquartile range 360-1440]. OIT as compared to control therapy significantly reduced the risk of the composite primary endpoint (hazard ratio [95% CI]= 0.62 [0.39-0.96], P= 0.03), without significant difference in terms of death/MI (0.84 [0.46-1.52], P= 0.57), death (1.12 [0.61-2.06], P= 0.71) and MI (0.67 [0.33-1.38], P= 0.28). OIT as compared to control therapy significantly reduced the risk of TLR (0.55 [0.34-0.89], P= 0.01) as well as the degree of in-stent LLL (0.62±0.65 mm versus 0.94±0.70 mm; mean difference 0.32 mm [0.22-0.42], P<0.001). The proportion of patients complaining side effects associated with OIT was 13.4% and 1.1% permanently discontinued the therapy. Conclusions: The use of oral immunosuppressive therapy as compared to control therapy reduces the composite of death/myocardial infarction or target lesion revascularization after stenting without safety issues. The advantage of oral immunosuppressive therapy is predominantly related to the lower risk of restenosis after revascularization.