Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA.
Circulation. 2013 Aug 20;128(8):823-33. doi: 10.1161/CIRCULATIONAHA.113.002303. Epub 2013 Jul 12.
Dual antiplatelet therapy in older versus younger patients with acute coronary syndromes is understudied. Low-dose prasugrel (5 mg/d) is recommended for younger, lower-body-weight patients and elderly patients with acute coronary syndromes to mitigate the bleeding risk of standard-dose prasugrel (10 mg/d).
A total of 9326 medically managed patients with acute coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial (<75 years of age, n=7243; ≥75 years of age, n=2083) were randomized to prasugrel (10 mg/d; 5 mg/d for those ≥75 or <75 years of age and <60 kg in weight) or clopidogrel (75 mg/d) plus aspirin for ≤30 months. A total of 515 participants ≥75 years of age (25% of total elderly population) had serial platelet reactivity unit measurements in a platelet-function substudy. Cumulative risks of the primary end point (cardiovascular death/myocardial infarction/stroke) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding increased progressively with age and were ≥2-fold higher in older participants. Among those ≥75 years of age, TIMI major bleeding (4.1% versus 3.4%; hazard ratio, 1.09; 95% confidence interval, 0.57-2.08) and the primary end point rates were similar with reduced-dose prasugrel and clopidogrel. Despite a correlation between lower 30-day on-treatment platelet reactivity unit values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for platelet reactivity unit values among participants ≥75 years of age in the platelet-function substudy (P=0.06). No differences in weight were seen in all participants ≥75 years of age with versus without TIMI major/minor bleeding in both treatment groups.
Older age is associated with substantially increased long-term cardiovascular risk and bleeding among patients with medically managed acute coronary syndromes, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared with clopidogrel in elderly patients. No significant interactions among weight, pharmacodynamic response, and bleeding risk were observed between reduced-dose prasugrel and clopidogrel in elderly patients.
URL: http://www.clinicaltrials.gov/ct2/home. Unique identifier: NCT0069999.
在急性冠脉综合征患者中，与年轻患者相比，老年患者的双联抗血小板治疗研究较少。为降低标准剂量普拉格雷（10mg/d）的出血风险，建议对较低体重的年轻患者和老年急性冠脉综合征患者使用低剂量普拉格雷（5mg/d）。
共有 9326 例接受药物治疗的急性冠脉综合征患者（TRILOGY ACS 试验，年龄<75 岁，n=7243；年龄≥75 岁，n=2083）被随机分配接受普拉格雷（10mg/d；对于≥75 岁或<75 岁且体重<60kg 的患者，使用 5mg/d）或氯吡格雷（75mg/d）+阿司匹林治疗，最长 30 个月。共有 515 名≥75 岁的患者（老年患者总数的 25%）参加了血小板功能亚研究，进行了一系列血小板反应单位测量。主要终点（心血管死亡/心肌梗死/卒中）和血栓形成溶栓（TIMI）大出血的累积风险随年龄的增加而逐渐增加，且老年患者的风险≥2 倍。在≥75 岁的患者中，与氯吡格雷相比，低剂量普拉格雷的 TIMI 大出血（4.1%比 3.4%；风险比，1.09；95%置信区间，0.57-2.08）和主要终点发生率相似。尽管在普拉格雷组中仅与体重较低的 30 天治疗时血小板反应单位值呈负相关，但在血小板功能亚研究中，≥75 岁的参与者中，血小板反应单位值的治疗与体重之间没有显著的相互作用（P=0.06）。在两组中，与无 TIMI 大出血/小出血的患者相比，≥75 岁的所有患者体重均无差异。
与年轻患者相比，接受药物治疗的急性冠脉综合征患者的年龄较大与长期心血管风险和出血风险显著增加相关，与氯吡格雷相比，老年患者使用低剂量普拉格雷并未改善缺血或出血结局。在老年患者中，未观察到低剂量普拉格雷和氯吡格雷之间在体重、药效学反应和出血风险之间存在显著的相互作用。
