Department of Cardiovascular Medicine, Saga University, Japan (M.N.).
Division of Cardiology, Hirakata Kohsai Hospital, Hirakata, Japan (H.W., H.T., T.Y., T.K.).
Circulation. 2024 Feb 20;149(8):585-600. doi: 10.1161/CIRCULATIONAHA.123.066720. Epub 2023 Nov 23.
Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials.
We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin.
The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; =0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; =0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group.
The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.
在经皮冠状动脉介入治疗(PCI)后 1 个月内,双重抗血小板治疗(DAPT)的出血率仍然很高,尤其是在急性冠状动脉综合征或高出血风险患者中。无阿司匹林策略可能会降低 PCI 后早期出血风险,而不会增加心血管事件,但在随机试验中尚未证明其疗效和安全性。
我们随机分配 6002 例急性冠状动脉综合征或高出血风险患者,在 PCI 前分别接受普拉格雷(3.75mg/天)单药治疗或 DAPT 治疗,阿司匹林(81-100mg/天)和普拉格雷(20mg 负荷量后 3.75mg/天)。主要终点是主要出血(Bleeding Academic Research Consortium 3 或 5)的优越性和心血管事件(心血管死亡、心肌梗死、明确支架血栓形成或缺血性卒中的复合终点)的非劣效性,相对风险差异为 50%。
全分析集人群包括 5966 例患者(无阿司匹林组 2984 例,DAPT 组 2982 例;年龄 71.6±11.7 岁;男性 76.6%;急性冠状动脉综合征 75.0%)。在随机分组前 7 天内,分别有 21.3%、6.4%、8.9%和 24.5%的患者接受了单独使用阿司匹林、阿司匹林联合 P2Y12 抑制剂、口服抗凝剂和静脉肝素输注。两组 1 个月时抗血小板治疗的依从率均为 88%。1 个月时,无阿司匹林组与 DAPT 组主要出血终点无显著差异(4.47%和 4.71%;风险比,0.95[95%CI,0.75-1.20];=0.66)。无阿司匹林组非劣效于 DAPT 组的主要心血管终点(4.12%和 3.69%;风险比,1.12[95%CI,0.87-1.45];=0.01)。两组间净临床不良结局和主要心血管终点的各组成部分无差异。无阿司匹林组任何计划性冠状动脉血运重建(1.05%和 0.57%;风险比,1.83[95%CI,1.01-3.30])和亚急性明确或可能的支架血栓形成(0.58%和 0.17%;风险比,3.40[95%CI,1.26-9.23])的发生率均高于 DAPT 组。
与 DAPT 策略相比,使用低剂量普拉格雷的无阿司匹林策略未能在 PCI 后 1 个月内证明主要出血的优越性,但在 PCI 后 1 个月内的心血管事件非劣效。然而,无阿司匹林策略与冠状动脉事件增加的信号相关。