Advertisement

The Reply

      We thank Chatterjee for his interest in our work.
      Most of the theoretical background that supports the systemic use of prednisone to prevent restenosis has been previously described by our group.
      • Ferrero V.
      • Ribichini F.
      • Pesarini G.
      • Brunelleschi S.
      • Vassanelli C.
      Therapeutic potential of glucocorticoids in the prevention of restenosis after coronary angioplasty.
      The main difference between previous negative investigations and the Cortisone plus BMS or DES versus BMS alone to eliminate restenosis (CEREA-DES) trial refers to the drug dose and treatment duration. In fact, unlike studies that tested low single doses or a 1-week treatment, we used prednisone at immunosuppressive doses for nearly 1 month, followed by an anti-inflammatory dose for 2 weeks. Reductions of this treatment scheme cause a loss of efficacy of prednisone after stenting.
      • Ferrero V.
      • Ribichini F.
      • Rognoni A.
      • Marino P.
      • Brunelleschi S.
      • Vassanelli C.
      Comparison of efficacy and safety of lower-dose to higher-dose oral prednisone after percutaneous coronary interventions (the IMPRESS-LD study).
      Steroids act on the monocyte/macrophages cell lines inhibiting monocyte production and transformation into mature macrophages. This reduces availability of monocytes able to enter the injured vessel wall to mediate the reparative processes that lead to neointimal growth. Furthermore, high doses of steroids inhibit monocyte-derived release of interleukins and cytokines that act as mediators of inflammation; these agents recall inflammatory cells, activated platelets, and proliferative smooth muscle cells leading to restenosis. The efficacy of this treatment in the atherosclerotic animal model with doses equivalent to those used in humans has been proven.
      • Ribichini F.
      • Joner M.
      • Ferrero V.
      • et al.
      Effects of oral prednisone after stenting in a rabbit model of established atherosclerosis.
      Details of the effective plasma drug concentration and its action on cytokines and intranuclear immuno-mediator NF-κB in humans have been previously demonstrated.
      • Pesarini G.
      • Amoroso A.
      • Ferrero V.
      • et al.
      Cytokines release inhibition from activated monocytes, and reduction of in-stent neointimal growth in humans.
      None of our patients received intravenous administration of steroids.
      Regarding patients selection, diabetic patients have been excluded from our studies because high doses of steroids cause hyperglycemia and may worsen the metabolic equilibrium of patients with subclinical forms of the disease. Patients with metabolic syndrome were not excluded from the study but represent a small percentage that does not allow a statistically meaningful analysis.
      Although high doses of steroids cause transient hyperglycemia, evidence showing that this is a clear risk factor for restenosis after stenting is inconsistent. Similarly, metabolic syndrome is not globally accepted as a clinical condition associated with significantly higher restenosis rates. In our experience, hyperglycemia was always transient and limited to the highest-dose period restricted to the first 2 weeks of treatment.
      The last comment refers to the use of statins. As described in detail in the study protocol, statins were started before percutaneous coronary intervention and titered to the maximum tolerated dose within the first follow-up control at 1 month. Patients' compliance to statin treatment was very high during the first year of follow-up, with more than 80% of patients still assuming the prescribed drug and dose in each of the study groups. In fact, the importance given to the optimization of the medical treatment, monitoring of patient's compliance to therapy, and secondary prevention is, in the authors' opinion, one of the reasons for the excellent clinical results observed in CEREA-DES.

      References

        • Ferrero V.
        • Ribichini F.
        • Pesarini G.
        • Brunelleschi S.
        • Vassanelli C.
        Therapeutic potential of glucocorticoids in the prevention of restenosis after coronary angioplasty.
        Drugs. 2007; 67: 1243-1255
        • Ferrero V.
        • Ribichini F.
        • Rognoni A.
        • Marino P.
        • Brunelleschi S.
        • Vassanelli C.
        Comparison of efficacy and safety of lower-dose to higher-dose oral prednisone after percutaneous coronary interventions (the IMPRESS-LD study).
        Am J Cardiol. 2007; 99: 1082-1086
        • Ribichini F.
        • Joner M.
        • Ferrero V.
        • et al.
        Effects of oral prednisone after stenting in a rabbit model of established atherosclerosis.
        J Am Coll Cardiol. 2007; 50: 176-185
        • Pesarini G.
        • Amoroso A.
        • Ferrero V.
        • et al.
        Cytokines release inhibition from activated monocytes, and reduction of in-stent neointimal growth in humans.
        Atherosclerosis. 2010; 211: 242-248

      Linked Article

      • Regarding Immunosuppressive Therapy to Prevent Restenosis after PCI
        The American Journal of MedicineVol. 125Issue 1
        • Preview
          We read with great interest the article by Ribichini et al1 about use of oral prednisone at immunosuppressive doses reducing recurrence of cardiovascular events for nondiabetic patients with elevated C-reactive protein at 1 year as well as lowering rates of target vessel revascularization and rates of restenosis. The same group had earlier reported encouraging findings with the Inhibition of Metaloprotease by Omapatarilat in a Randomized Exercise and Symptoms Study of Heart Failure (IMPRESS) study.
        • Full-Text
        • PDF