National Center of Cardiovascular Investigations Carlos III (CNIC), Madrid, Spain.
Department of Cardiology, Hamilton Health Sciences, Hamilton, Ontario, Canada.
J Am Coll Cardiol. 2023 Aug 22;82(8):687-700. doi: 10.1016/j.jacc.2023.05.062.
In TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention), among high-risk patients undergoing percutaneous coronary intervention (PCI), ticagrelor monotherapy vs continuation of dual antiplatelet therapy (DAPT) with aspirin and ticagrelor after completing a 3-month course of DAPT was associated with reduced bleeding, without an increase in ischemic events.
This investigation sought to study the clinical benefit of ticagrelor monotherapy vs DAPT by simultaneously modeling its associated potential bleeding benefits and ischemic harms on an individual patient basis.
Multivariable Cox regression models for: 1) Bleeding Academic Research Consortium type 2, 3, or 5 (BARC-2/3/5); and 2) cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke (major adverse cardiac and cerebrovascular event [MACCE]) were developed using stepwise forward variable selection. The coefficients in the BARC-2/3/5 and MACCE models were used to calculate bleeding and ischemic risk scores, respectively, for each patient (excluding the coefficient for randomized treatment).
In the total study group (N = 7,119), BARC-2/3/5 occurred in 391 (5.5%) patients, and MACCE occurred in 258 (3.6%). There was a consistent reduction in bleeding events associated with ticagrelor monotherapy compared with DAPT across both bleeding and ischemic risk strata (P interaction = 0.54 and 0.11, respectively). Importantly, this benefit associated with ticagrelor monotherapy was not offset by an increase in MACCE at any level of bleeding or ischemic risk.
Three months after PCI, discontinuing aspirin and maintaining ticagrelor monotherapy reduces bleeding in both higher-bleeding risk and lower-bleeding risk patients compared with continued DAPT. This benefit does not appear to be offset by greater ischemic risk. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).
在 TWILIGHT（替格瑞洛联合阿司匹林或单独用于冠状动脉介入治疗高危患者）研究中，与完成 3 个月 DAPT 疗程后继续接受阿司匹林和替格瑞洛双联抗血小板治疗（DAPT）的患者相比，接受经皮冠状动脉介入治疗（PCI）的高危患者中，替格瑞洛单药治疗与减少出血相关，而不会增加缺血事件。
本研究旨在通过同时基于个体患者的潜在出血获益和缺血危害对替格瑞洛单药治疗与 DAPT 进行建模，以研究替格瑞洛单药治疗的临床获益。
采用逐步向前变量选择方法，建立多变量 Cox 回归模型，用于：1）BARC-2/3/5 型出血（BARC-2/3/5）；和 2）心血管死亡、非致死性心肌梗死和非致死性缺血性卒中（主要不良心脑血管事件 [MACCE]）。在排除随机治疗的系数后，BARC-2/3/5 和 MACCE 模型中的系数分别用于计算每位患者的出血和缺血风险评分。
在总研究人群（N=7119）中，391 例（5.5%）患者发生 BARC-2/3/5 型出血，258 例（3.6%）患者发生 MACCE。与 DAPT 相比，替格瑞洛单药治疗与各出血和缺血风险分层中出血事件的减少相关（P 交互=0.54 和 0.11）。重要的是，在任何出血或缺血风险水平，替格瑞洛单药治疗与 MACCE 增加无关，且这种获益不受影响。
在 PCI 后 3 个月，与继续 DAPT 相比，停用阿司匹林并维持替格瑞洛单药治疗可降低较高出血风险和较低出血风险患者的出血风险。这种获益似乎并未因缺血风险增加而抵消。（替格瑞洛联合阿司匹林或单独用于冠状动脉介入治疗高危患者 [TWILIGHT]；NCT02270242）。
