title: ORAl iMmunosuppressive therapy to prevent in-Stent rEstenosiS (RAMSES) cooperation: a patient-level meta-analysis of randomized trials.
abstract: OBJECTIVE
  The role of oral immunosuppressive therapy (OIT) to prevent restenosis after percutaneous coronary intervention (PCI) and stenting is still controversial. This study evaluates the impact of oral administration of prednisone or sirolimus to prevent restenosis.
  
  
  METHODS
  We conducted a meta-analysis of trials in which PCI-patients were randomized to bare metal stents (BMS) plus OIT (BMS + OIT group) versus BMS or drug-eluting stents alone (BMS/DES group). Primary endpoints were target lesion revascularization and death/myocardial infarction (MI). Secondary endpoints were death, MI, stent thrombosis and in-stent late lumen loss. Hazard ratio and weighted geometric mean difference [95% confidence intervals] served as summary statistics.
  
  
  RESULTS
  Individual data of seven trials (1246 patients [BMS + OIT, n = 608 versus BMS/DES, n = 638] with 1456 coronary lesions) were merged. At a median follow-up of 360 days, BMS + OIT versus BMS/DES significantly reduced the risk of revascularization (0.49 [0.24-0.98], P = 0.04). In particular, BMS + OIT reduced the risk of revascularization (0.38 [0.21-0.67], P < 0.001) and late lumen loss (-0.39 mm [-0.67, -0.11], P < 0.001) as compared with BMS alone. BMS + OIT versus BMS/DES showed a similar risk of death/MI (0.67 [0.29-1.53], P = 0.34), death (0.82 [0.25-2.69], P = 0.71), MI (0.58 [0.24-1.39], P = 0.22) and stent thrombosis (0.43 [0.10-1.87], P = 0.26).
  
  
  CONCLUSIONS
  In patients undergoing PCI the use of BMS and oral immunosuppressive therapy reduces the risk of revascularization as compared with BMS alone but not as compared with DES alone, while these therapies display a similar risk of death/MI. The advantage of adding oral immunosuppressive therapy to BMS is due to a lower risk of restenosis as compared with BMS alone.
authors.affiliation: Deutsches Herzzentrum, Technische Universität München, Lazarettstr. 36, 80636 Munich, Germany. Electronic address: cassese@dhm.mhn.de.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cassese
authors.affiliation: Department of Clinical and Experimental Medicine, Eastern Piedmont University, Novara, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
authors.affiliation: Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Ribichini
authors.affiliation: Interventional Cardiology, San Gaudenzio Clinic, Novara, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Cernigliaro
authors.affiliation: Catheterization Laboratory, Division of Cardiology, Maggiore Hospital, Novara, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Sansa
authors.affiliation: Department of Cardiology, Cardarelli Hospital, Campobasso, Italy; Department of Cardiology, Veneziale Hospital, Isernia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Versaci
authors.affiliation: Department of Cardiology, Vannini Hospital, Rome, Italy.
authors.forename: Igino
authors.initials: I
authors.lastname: Proietti
authors.affiliation: Department of Diagnostics and Catheterization Laboratory, Division of Cardiology, Clinical Center of Serbia, Medical School of Belgrade, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Stankovic
authors.affiliation: Department of Diagnostics and Catheterization Laboratory, Division of Cardiology, Clinical Center of Serbia, Medical School of Belgrade, Serbia.
authors.forename: Sinisa
authors.initials: S
authors.lastname: Stojkovic
authors.affiliation: Cardiovascular Research Center, Sanatorio Otamendi, Buenos Aires, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Pereira
authors.affiliation: Department of Cardiovascular Sciences, European Hospital, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tomai
authors.affiliation: Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Vassanelli
authors.affiliation: Division of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Antoniucci
authors.affiliation: Thorax Center, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.affiliation: Deutsches Herzzentrum, Technische Universität München, Lazarettstr. 36, 80636 Munich, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.affiliation: Cardiovascular Research Center, Sanatorio Otamendi, Buenos Aires, Argentina.
authors.forename: Alfredo E
authors.initials: AE
authors.lastname: Rodriguez
mesh_terms: D000284:Administration, Oral; D000368:Aged; D023903:Coronary Restenosis / Q000517:prevention & control*; D054855:Drug-Eluting Stents / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008670:Metals / Q000737:chemistry; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000008:administration & dosage; D015607:Stents / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D008670:Metals; D011241:Prednisone; D020123:Sirolimus
keywords: Coronary stents; Meta-analysis; Oral immunosuppressive therapy; Restenosis