| Sumario: | Restenosis is one of the most important problems limiting the long-term success of coronary angioplasty. Use of stents has successfully reduced the problem of restenosis, on average from 22 % to 32 %, although with higher values for patients in high risk groups. The use of stents however, has led to the challenge of handling in-stent restenosis. In-stent restenosis is the result of a process called intima hyperplasia whereby local cell activation and inflammation stimulates growth of smooth muscle cells and deposition of extracellular matrix within the vessel lumen. Approaches to combat the problem of restenosis such as systemic or local drug administration or intracoronary brachytherapy have had modest success. A recent approach is the use of drug eluting stents (DES) that may interfere with the proliferative response leading to in-stent restenosis. Drug eluting stents provide a local drug reservoir that is released within a time period of 10-30 days, with no detectable systemic drug levels. Several antiproliferative agents added to different stents are under clinical investigation. Rapamycins, which includes the drugs Sirolimus, Everolimus and Tacrolimus, are immunosuppressive agents that inhibit proliferation of smooth muscle cells. Taxol-based drugs, such as 7-hexaonyltaxol or paclitaxel are cytotoxic drugs that interfere with cell proliferation, and are currently used in cancer chemotherapy. Following the recent approval of two types of drug-eluting stents in Europe and North America, drug eluting stents are rapidly disseminating throughout the health care systems in several countries. The uptake is advocated by great enthusiasm following positive results from randomised controlled trials. COMMENTS: Two main findings emerged from the systematic review and metaanalysis of these trials. Drug eluting stents and intracoronary brachytherapy reduced rates of revascularisation. However, possible effect on clinical outcomes such as mortality is at present insufficiently addressed. When new technologies are introduced into clinical practice, the question of clinical effectiveness and the safety of the technology need to be adressed, to ensure that patients are given efficient and safe treatment. This is especially challenging when considering fast evolving technologies such as drug eluting stents. The past history of abandoned studies calls for caution regarding the potential offset between benefit and harm. The life-span of a systematic review in a fast evolving field such as drug eluting stents is short. Several ongoing trials accounting for over 8000 patients will make important contributions regarding clinical effectiveness of this technology. The results from this systematic review may also have implications for the future reporting of outcomes from ongoing and planned clinical trials, especially the use of composite endpoints. Use of MACE as the hierarchical combination of death, myocardial infarction and revascularisation is misleading, both due the possibility of divergent effects of individual outcomes, and due to the fact that revascularisation counts equally with mortality.
|
|---|
