Oral platelet glycoprotein IIb/IIIa receptor inhibitors--part II.
Although the hypothesis of benefit from prolonged oral IIb/IIIa inhibition was appealing, the large Phase III trials have uniformly shown there was no improvement in outcome. In addition, there was an increased mortality seen in patients treated with the oral IIb/IIIa inhibitor. This latter finding is not adequately explained, but is likely a multifactorial problem of this strategy of platelet inhibition. The trials found that, even with no improvement in efficacy, there was increased bleeding, meaning that for chronic therapy with IIb/IIIa inhibition there does not appear to be a therapeutic window. Accordingly, chronic oral IIb/IIIa inhibition appears to have been well tested but has not worked. Fortunately, there are several other oral antiplatelet agents available that have shown beneficial results, including clopidogrel. In addition, other newer classes of antiplatelet agents are in earlier stages of development. Thus, agents targeted more "upstream" in platelet activation pathways may offer a more tolerable and efficacious approach to long-term antiplatelet therapy.
Cannon
Christopher P
CP
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. cpcannon@partners.org
D000208:Acute Disease; D000284:Administration, Oral; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D013577:Syndrome
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex