Leviev Heart Center, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel.
JAMA Cardiol. 2017 Dec 1;2(12):1380-1384. doi: 10.1001/jamacardio.2017.3868.
Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation.
To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI.
DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat.
Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose.
P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD.
Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99).
Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes.
clinicaltrials.gov Identifier: NCT02725099.
替格瑞洛是一种直接作用的 P2Y12 抑制剂,与氯吡格雷和普拉格雷不同,它不需要代谢激活,双抗血小板治疗是治疗 ST 段抬高型心肌梗死(STEMI)患者的标准治疗方法。
评估在 STEMI 患者中,咀嚼负荷剂量(LD)替格瑞洛 180mg 与传统口服等剂量相比,是否能在 LD 给药后 30 分钟和 1 小时增强血小板抑制作用。
设计、地点和参与者:这是一项在 2016 年 5 月至 10 月期间在一家大型三级保健中心进行的随机临床试验,纳入了 30 至 87 岁的成年人。分析采用意向治疗。
50 例 STEMI 患者被随机分为咀嚼替格瑞洛 LD 180mg 组或标准口服等剂量组。
在 LD 前、30 分钟、1 小时和 4 小时使用 VerifyNow(Accumentrics)评估 P2Y12 反应单位。
两组患者的基线特征相似。在替格瑞洛 LD 后,咀嚼组的 P2Y12 反应单位平均值(标准差)与标准组相比,分别为基线时 224(33)对 219(44)(95%置信区间,-16.77 至 27.73;P=0.26)、30 分钟时 168(78)对 230(69)(95%置信区间,-103.77 至-19.75;P=0.003)、1 小时时 106(90)对 181(89)(95%置信区间,-125.15 至-26.29;P=0.005)和 4 小时时 43(41)对 51(61)(95%置信区间,-36.34 至 21.14;P=0.30)。LD 后 30 分钟,咀嚼组的血小板反应性显著降低 24%(95%置信区间,19.75 至 103.77;P=0.001)。在 1 小时时,咀嚼组与标准组的血小板聚集抑制相对比为 51%对 10%(95%置信区间,13.69 至 67.67;P=0.005),在 4 小时时为 81%对 76%(95%置信区间,-12.32 至 16.79;P=0.24)。30 天内主要不良心脏和心血管事件发生率较低(4%),两组各有 1 例(95%置信区间,0.06 至 16.93;P>0.99)。
在 STEMI 患者中咀嚼 LD 替格瑞洛 180mg 是可行的,与标准口服 LD 相比,能更好地早期抑制血小板。需要更大的研究来观察我们的初步发现是否转化为临床结果。
clinicaltrials.gov 标识符:NCT02725099。