替格瑞洛降低心血管死亡率课件.ppt

* Title: Regardless of How ACS Presents, Post-discharge Mortality Remains High Key Points: For patients with atherothrombotic disease, post ACS-event mortality remains high (results from the GRACE registry) The GRACE registry data indicates up to 15% of patients with ACS may die within 12 months of their initial event Post-ACS events continue to occur and increase over time following discharge regardless of diagnosis, leaving room for improvement in the treatment of ACS Additional Information: The GRACE registry is a large-scale, multinational, observational study established in 1999 to provide reliable and precisely defined data on the treatment, practice patterns, and long-term outcomes of patients with ACS. A total of 115 hospitals, located in 14 countries (Australia, New Zealand and various countries in North and South America and Europe) have contributed data to this study Eligible patients are adults (≥18 years old) admitted to participating hospitals with a presumptive diagnosis of ACS and a clinical history of ACS accompanied by at least one of the following: electrocardiographic changes consistent with ACS, serial increases in levels of biochemical markers of cardiac necrosis and documented coronary artery disease. Between the start of July 1999 and the end of June 2006, 46,829 patients with confirmed ACS were enrolled Within the first 15 days of presentation with ACS, patients with ST-segment elevation at initial presentation are at greatest risk of death 38% of patients had ST-segment elevation, 18% had ST-segment depression, and 44% had neither Reference: Fox KA, Anderson FA Jr, Goodman SG, et al. Time course of events in acute coronary syndromes: implications for clinical practice from the GRACE registry. Nat Clin Pract Cardiovasc Med. 2008;5:580–589. ATP是ADP诱导聚集的内源性P2Y12竞争性拮抗剂，但ATP呈非选择性，非常不稳定且效力低，因此临床上迫切需要寻找稳定的、高亲和力的类似物。 以内源性P2Y12受体抑制剂ATP为母体，通过修饰腺嘌呤引入脂溶性的含硫取代基，增加药物与受体的亲和力，从而得到静脉制剂坎格雷洛药物。由于ATP分子结构中三磷酸基团半衰期短，为了进一步提高药物的半衰期，替格瑞洛分子中将三磷酸基团替换为活性类似的羟基基团，