[The Ravel trial. Zero percent restenosis: A cardiologists dream comes true!].

Since the introduction of coronary angioplasty, every advance has been shadowed by the phenomenon known as «restenosis». Attempts to avoid the vascular reaction naturally generated by «mother nature» in response to the vascular damage induced by catheterization have either failed or had only limited success. Nevertheless, the findings of the recently published RAVEL study seem to indicate that the dream of generations of cardiologists seems to have come true and restenosis has been relegated to the kingdom of nightmares and fairy tales. Such «sweet dreams» are made of «rapamycin» Rapamycin (sirolimus) is a drug that has been approved by the FDA (Food and Drug Administration) for the prophylaxis of rejection in renal transplantation (Rapamune ®) since 1999. It is a natural macrocyclic lactone that blocks the passage from G1 to S in the cell cycle, and interacts with a specific target protein (mTOR [mammalian Target Of Rapamycin]) to inhibit its activation. Inhibition by mTOR (FK506-binding protein 12) suppresses T-cell proliferation induced by cytokines (IL-2, IL-4, IL-7 and IL-15). The mTOR protein is a key kinase regulator and its inhibition produces several important effects, including: a) inhibition of the translation of a messenger RNA family that encodes proteins essential to the progression of the cell cycle; b) IL-2 induced inhibition of the transcription of proliferating cell nuclear antigen (PCNA), which is essential for DNA replication; c) blockade of CD28-mediated up-regulation of IL-2 transcription in T cells, and d) inhibition of the kinase activity of cdk4/cyclin D and cdk2/cyclin E complexes, essential for progression of the cell cycle. Its mechanism of action is different from that of other immunosuppressive agents that only act to inhibit DNA synthesis, such as mycophenolate mofetil (CellCept ®) and azathioprine (Imuran ®). Rapamycin has a synergic action with cyclosporin A and much less toxicity than other immunosuppressive drugs. The sirolimus-coated stent «BX velocity» (Cypher) is manufactured from medical stainless steel (316 LS) and measures 18 mm in length. This stent contains 140 mg/cm 2 of rapamycin, for a total rapamycin content of 153 mg in the 6-cell stent and 180 mg in the 7-cell stent. The formulation of the coating consists of 30% rapamycin by weight in a 50% polymer mixture: polyethylene vinyl acetate (PEVA) and polybutylmethacrylate acetate (PBMA). The first experimental studies demonstrated that rapamycin impeded the proliferation of T cells and the proliferation 1 and migration of smooth muscle cells. Studies of its effectiveness in …