Smitherman T C
Division of Cardiology, 3498 Presbyterian University Hospital, University of Pittsburgh Medical Center, PA 15213.
Mol Biol Med. 1991 Apr;8(2):207-18.
The data reviewed above show that the ideal thrombolytic or thrombolytic plus anticoagulant regimen does not exist. Nor is it clear to me that one regimen is unequivocally better than another in regards to clinical outcome. Publication of the full results of the ISIS-3 study and completion of the TAPS study, the GUSTO study, the TIMI-4 study plus others only now in the planning phases, should help. This review will not stay current very long. These data do, however, give some guides to certain circumstances in which one regimen might be preferred over others. If economics is a compelling issue, as it may be in public hospitals on a fixed budget or in the developing world, streptokinase may be the best choice. For early application of thrombolytic therapy, such as at the site of infarct occurrence and in automotive and aerial ambulances, anistreplase may be preferred because of its ease of administration. Previous administration of streptokinase or anistreplase (within the period of 48 h to 6 months after prior use) militate against their use as does a recent streptococcal infection. Heightened concerns about bleeding risk, except intracranially, in the absence of absolute contraindication of fibrinolytic therapy, e.g. remote gastrointestinal hemorrhage or the expected imminent need for an invasive procedure, may lead to preference for alteplase over streptokinase or anistreplase. On the other hand, heightened concerns about intracranial hemorrhage may lead to preference for streptokinase over alteplase or anistreplase. Alteplase may be preferred over non-fibrin-selective agents in the treatment of patients when administration is begun more than three hours after the presumed onset of infarction. These considerations notwithstanding, it is crucial that debates over the best choice of a regimen must not be allowed to prolong the time before administration of an effective thrombolytic agent to a patient with evolving Q-wave infarction who is a good candidate for this therapy. This review may also become dated in the not-too-distant future because of expected further advances in thrombolytic regimen. Application of new antithrombotic regimens was noted above. Future thrombolytic and antithrombotic regimens may be "cocktails" of one or more thrombolytic agents plus more powerful antithrombotic and antiplatelet agents. New generations of thrombolytic agents may replace the current first and second generation agents now used. Combination thrombolytic and anti-fibrin antibody agents and mutant tissue-type plasminogen activators with lower affinity for plasminogen activator inhibitor and longer half-lives are being developed.(ABSTRACT TRUNCATED AT 400 WORDS)
上述回顾的数据表明,理想的溶栓或溶栓加抗凝方案并不存在。而且在我看来,就临床结果而言,一种方案是否绝对优于另一种方案也并不明确。ISIS - 3研究完整结果的发表以及TAPS研究、GUSTO研究、TIMI - 4研究(还有其他目前尚处于规划阶段的研究)的完成或许会有所帮助。但这篇综述不会长时间保持时效性。然而,这些数据确实为某些情况下哪种方案可能优于其他方案提供了一些指导。如果经济因素是一个紧迫问题,比如在预算固定的公立医院或发展中国家,链激酶可能是最佳选择。对于溶栓治疗的早期应用,例如在梗死发生地以及在汽车和空中救护车上,由于其易于给药,茴香酰化纤溶酶原链激酶复合物(阿尼普酶)可能更受青睐。先前使用过链激酶或阿尼普酶(在先前使用后的48小时至6个月内)会妨碍再次使用,近期的链球菌感染也是如此。在没有纤维蛋白溶解疗法绝对禁忌证的情况下,例如既往胃肠道出血或预计即将需要进行侵入性操作时,除颅内出血外,对出血风险的担忧加剧,可能会导致更倾向于选择阿替普酶而非链激酶或阿尼普酶。另一方面,对颅内出血的担忧加剧可能会导致更倾向于选择链激酶而非阿替普酶或阿尼普酶。在推测梗死发作超过三小时后开始给药时,阿替普酶在治疗患者方面可能比非纤维蛋白选择性药物更受青睐。尽管有这些考虑因素,但至关重要的是,对于方案最佳选择的争论绝不能延长向适合这种治疗的进展期Q波梗死患者施用有效溶栓剂之前的时间。由于溶栓方案预计会有进一步进展,这篇综述在不久的将来可能也会过时。上文提到了新抗血栓方案的应用。未来的溶栓和抗血栓方案可能是一种或多种溶栓剂加上更强效的抗血栓和抗血小板药物的“鸡尾酒”组合。新一代溶栓剂可能会取代目前正在使用的第一代和第二代药物。正在研发溶栓和抗纤维蛋白抗体联合制剂以及对纤溶酶原激活物抑制剂亲和力更低、半衰期更长的突变型组织型纤溶酶原激活剂。(摘要截选至400词)