Eccleston D S, Horrigan M C, Ellis S G
Department of Cardiology, Cleveland Clinic Foundation, Ohio 44195, USA.
Semin Interv Cardiol. 1996 Mar;1(1):8-16.
Although advances during the last decade have transformed the management of coronary artery disease, deficiencies in our understanding of the basic processes of arterial thrombosis and restenosis after percutaneous intervention continue to present major challenges to their prevention. While coronary stenting has in selected cases provided the first effective approach to the problem of restenosis, new devices such as atherectomy have largely proven ineffective in this field. Similarly, despite evidence that many pharmacological agents reduce neointimal hyperplasia in experimental models, in clinical trials these agents have failed to attenuate the restenotic process. This may reflect patients' inability to tolerate the high systemic drug concentrations required to achieve adequate levels for sufficient time at the target site, necessitating a shift in the focus of therapeutic agents for the prevention of thrombosis and restenosis to local or site-specific delivery. The major advantage that local drug delivery may potentially provide is the ability to achieve high and sustained local concentrations of drug without large systemic doses, thus minimizing systemic toxicity.
尽管过去十年的进展改变了冠状动脉疾病的治疗方式，但我们对经皮介入后动脉血栓形成和再狭窄基本过程的理解不足，仍然给预防这些问题带来重大挑战。虽然冠状动脉支架置入术在某些情况下为解决再狭窄问题提供了首个有效方法，但诸如旋切术等新设备在该领域大多已被证明无效。同样，尽管有证据表明许多药物制剂在实验模型中可减少内膜增生，但在临床试验中这些药物未能减轻再狭窄过程。这可能反映出患者无法耐受在目标部位达到足够水平所需的高全身药物浓度，并持续足够长的时间，因此需要将预防血栓形成和再狭窄的治疗药物重点转向局部或部位特异性给药。局部药物递送可能潜在提供的主要优势是能够在不使用大剂量全身药物的情况下实现高且持续的局部药物浓度，从而将全身毒性降至最低。
