FDA的药品评价和研究中心心血管和肾产品部主任Norman Stockbridge, M.D., Ph.D.说“在临床试验中, Brilinta在防止心脏病发作和死亡方面比Plavix[氯吡格雷]更有效，但优点是与阿司匹林[aspirin]维持剂量75至100毫克每天1次时见到。”
批准日期：2011年7月20日；公司：AstraZeneca
随着抗血小板聚集药物快速发展，越来越多的抗血小板聚集药物进入临床。阿斯利康研发的新型抗凝药——替卡格雷更是有望成为格雷类口服抗血小板聚集和抗血栓类鼎足药物。
替卡格雷是一种新型的、具有选择性的小分子抗凝血药，也是第一个可逆的结合型口服P2Y12腺苷二磷酸受体拮抗剂，能可逆性地作用于血管平滑肌细胞(VSMC)上的嘌呤2受体亚型P2Y12，对ADP引起的血小板聚集有明显的抑制作用，能有效改善急性冠心病患者的症状。因为替卡格雷的可逆性抗血小板作用，尤为适用于那些需在先期进行抗凝治疗后再行手术的病人。
用小鼠的主动脉环进行的研究发现，氯吡格雷不能阻断血管平滑肌细胞收缩，可能是因为其活性代谢物在循环系统中极不稳定而不能起效；而替卡格雷可以阻断由P2Y12受体介导的ADP引起的血管平滑肌细胞收缩，即使是先使用氯吡格雷后发生收缩的血管平滑肌在加用替卡格雷后，收缩也会受到进一步抑制。空白对照组和氯吡格雷组的最大收缩率分别为59％和64％；当给予替卡格雷后，两组的收缩率分别达到33％和32％。
一项名为DISPERSE的多中心的Ⅱa期试验中，200名患有稳定型动脉粥样硬化的病人被随机给予替卡格雷(50，100或200mg，hid，或400mg，qd)或氯吡格雷(75mg，qd)加阿司匹林(75—100mg，qd)，用药时间为28天。结果表明，与氯吡格雷相比，替卡格雷(100mg或以上，bid)的起效更快、更持久、对血小板凝集的抑制作用更强(90％vs60％)。
所有使用替卡格雷患者对该药都能很好地耐受；使用替卡格雷药造成的所有出血事件大多不甚严重，只有在最大用药量(400mg，qd)时，出现1例比较大的出血事件；替卡格雷组有呼吸困难的情况出现，且发生率呈剂量依赖性：5O和100mg(bid)组的发生率为10％、200mg(bid)组为16％．400mg(qd)组则为20％，但情况并不严重，亦未发生与心力衰竭、支气管痉挛等相关的症状。由不良事件而导致的停药呈剂量相关，随着替卡格雷的剂量从5Omg，bid上升到400mg，qd，停药率从2．5％增加到8．6％，而氯吡格雷的停药率为2．7％。
抗凝剂市场去年全球销售额高达140多亿美元，近5年来以平均近10%的增长率快速扩增，成为各大制药巨头的必争之地。昨天，阿斯利康公司的抗凝新药Brilinta以7:1的投票结果获得FDA专家小组的批准推荐，有望成为抗凝剂市场的新宠，也使得抗凝剂市场竞争愈加激烈。
Manufacturer:
AstraZeneca Pharmaceuticals

Pharmacological Class:
P2Y12 platelet inhibitor (cyclopentyltriazolopyrimidine).

Active Ingredient(s):
Ticagrelor 90mg; tablets.

Indication(s):
To reduce the rate of thrombotic cardiovascular (CV) events in patients with acute coronary syndrome (ACS) (unstable angina or non-ST-elevation myocardial infarction [MI] or ST-elevation MI).

Pharmacology:
Ticagrelor is a platelet activation and aggregation inhibitor mediated by the P2Y12 class of ADP receptors. Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation. Both ticagrelor and its active metabolite are approximately equipotent.

Clinical Trials:
In a randomized, double-blind study, the use of ticagrelor was compared to a regimen of clopidogrel, both given in combination with aspirin and other standard therapy in patients with acute coronary syndromes. Patients were treated for at least 6 months and for up to 12 months.

The primary endpoint was the composite of first occurrence of cardiovascular death, non-fatal MI (excluding silent MI), or non-fatal stroke. The components were assessed as secondary endpoints.

At study completion, ticagrelor has been shown to significantly reduce the rate of a combined endpoint of cardiovascular death, MI or stroke compared to clopidogrel (9.8% vs. 11.7%, respectively, hazard ratio [HR] 0.84). The difference between treatments on the composite resulted from effects on CV death (HR 0.79) and MI (HR 0.84); each was statistically significant when considered as a secondary endpoint and there was no difference on strokes. There was also a decrease in all-cause mortality.

Among 11,298 patients with PCI receiving any stent during this study, there was a lower risk of stent thrombosis (1.3% for adjudicated “definite”) than with clopidogrel (1.9%).

Legal Classification:
Rx