Efficacy and Safety of Ticagrelor: A Reversible P2Y12 Receptor Antagonist
Efficacy and Safety of Ticagrelor: A Reversible P2Y12 Receptor Antagonist
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DOI：
10.1345/aph.1m548
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发表时间：
2010-03-01
影响因子：
2.9
通讯作者：
Epstein, Benjamin J.
中科院分区：
文献类型：
--
作者：
Anderson, Shawn D.;Shah, Niren K.;Epstein, Benjamin J.
目的：总结选择性P2Y12受体拮抗剂替格瑞洛的药代动力学和药效学特性，评价其在治疗急性冠脉综合征（ACS）患者中的作用。 数据来源：文献检索MEDLINE（1966年-2009年11月）、International Pharmaceutical Abstracts（1970年-2009年11月）和EMBASE（1990年-11月） 2009）使用 MeSH 术语和关键词 AZD6140、替格瑞洛、P2Y12 受体拮抗剂、心血管疾病、ACS、动脉粥样硬化血栓形成和血小板。研究选择和数据提取：选定的研究评估了替格瑞洛治疗 ACS 的药理学、药代动力学、药效学、安全性和有效性。数据合成：替格瑞洛选择性和可逆性阻断P2Y12 受体，抑制血小板聚集并防止血小板活化放大。根据替格瑞洛的药代动力学和药效学特征确定的最佳剂量策略是负荷剂量为 180 mg，随后口服 90 mg，每日两次。在这些剂量下，在接受过氯吡格雷治疗的患者和未接受过氯吡格雷治疗的患者中，与氯吡格雷 75 mg 每日一次相比，替格瑞洛可观察到更强的血小板抑制作用。针对 ACS 患者的研究得出结论，与氯吡格雷相比，替格瑞洛与 ACS 标准疗法相比，可降低心血管死亡率、非致命性心肌梗塞、支架内血栓形成和总体死亡率，且不会增加大出血。与氯吡格雷相比，替格瑞洛的卒中风险没有显着差异；然而，替格瑞洛的颅内出血更为常见。替格瑞洛耐受性良好；然而，与氯吡格雷相比，轻微出血、呼吸困难、低血压、恶心和心室停搏的发生率更高。替格瑞洛的可逆抑制可能允许在停药后进行更快速的手术干预，这表明 ACS 治疗具有更大的灵活性。结论：替格瑞洛改善的药代动力学和药效学特征是建立在目前可用的 P2Y12 受体拮抗剂的局限性之上的。替格瑞洛是预防 ACS 患者心血管事件的一种有前景的方法。
OBJECTIVE: To summarize the pharmacokinetic and pharmacodynamic properties of ticagrelor, a selective P2Y12 receptor antagonist, and evaluate its role in the treatment of patients with acute coronary syndromes (ACS).DATA SOURCES: A literature search was conducted in MEDLINE (1966-November 2009), International Pharmaceutical Abstracts (1970-November 2009), and EMBASE (1990-November 2009) using the MeSH terms and key words AZD6140, ticagrelor, P2Y12 receptor antagonist, cardiovascular disease, ACS, atherothrombosis, and platelets.STUDY SELECTION AND DATA EXTRACTION: Selected studies evaluated the pharmacology, pharmacokinetics, pharmacodynamics, safety, and efficacy of ticagrelor for the treatment of ACS.DATA SYNTHESIS: Ticagrelor selectively and reversibly blocks the P2Y12 receptor, inhibiting platelet aggregation and preventing amplification of platelet activation. Optimal dosing strategy as determined by ticagrelor's pharmacokinetic and pharmacodynamic profile is a loading dose of 180 mg followed by 90 mg by mouth twice daily. At these doses, greater platelet inhibition is observed with ticagrelor as compared to clopidogrel 75 mg once daily in both clopidogrel-experienced and -naive patients. Studies in patients experiencing ACS concluded that ticagrelor reduced the rate of cardiovascular death, nonfatal myocardial infarction, stent thrombosis, and overall mortality compared to clopidogrel without increasing major bleeding when administered with standard therapy for ACS. There was no significant difference in the risk of stroke with ticagrelor compared to clopidogrel; however, intracranial bleeding was more common with ticagrelor. Ticagrelor is well tolerated; however, minor bleeding, dyspnea, hypotension, nausea, and ventricular pauses were reported more frequently than with clopidogrel. Reversible inhibition with ticagrelor may allow for more rapid surgical intervention after discontinuation, suggesting greater flexibility in treatment of ACS.CONCLUSIONS: Ticagrelor's improved pharmacokinetic and pharmacodynamic profile builds upon the limitations of currently available P2Y12 receptor antagonists. Ticagrelor represents a promising approach for the prevention of cardiovascular events in patients with ACS.