Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York; Cardiovascular Research Foundation, New York, New York.
Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York.
JACC Cardiovasc Interv. 2015 Dec 28;8(15):1978-1987. doi: 10.1016/j.jcin.2015.08.032.
This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation.
Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes.
In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU).
The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality.
In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794).
本研究旨在确定在接受成功药物洗脱支架植入的 8582 例患者的大型多中心 ADAPT-DES（药物洗脱支架双重抗血小板治疗评估）研究中，血小板反应性（PR）的理想水平是否能优化安全性和疗效。
氯吡格雷治疗后 PR 较高的患者支架植入后发生不良缺血事件的发生率更高，而 PR 较低可能会增加出血风险。由于样本量有限，以前的研究无法调整可能影响 PR 与结果关系的基线特征差异。
在 ADAPT-DES 研究中，在氯吡格雷负荷后进行常规血小板功能检测（VerifyNow）。为了描述 PR 与临床事件之间的独立关联，将患者按 P2Y12 反应单位（PRU）五分位进行分层。
5 个五分位的 PRU 中位数分别为 57、130、187、244 和 317（抑制程度从高到低）。PRU 五分位值逐渐升高与支架血栓形成呈单调相关，而对于临床相关出血，最低 PRU 五分位的风险最大，而 4 个较高的五分位的风险相似。这些关系在完全调整的多变量分析中仍然显著（与 Q1 相比，Q5 的支架血栓形成调整后危险比 [HR]：2.32；95%置信区间 [CI]：1.17 至 4.59；p = 0.02；与 Q1 相比，Q5 的临床相关出血调整后 HR：0.61；95%CI：0.47 至 0.77；p<0.001）。然而，PRU 水平与死亡率之间没有显著的独立关联。
在这项大型观察性研究中，PRU 的增加与支架血栓形成呈单调增加相关，而出血风险仅限于最低 PRU 五分位，这表明在中等抑制的 PRU 下，血小板抑制的治疗窗最佳。然而，在调整后的分析中，PRU 和死亡率没有显示出明显的阈值效应，这可能是由于整个血小板抑制范围内出血和缺血的抵消影响。（药物洗脱支架双重抗血小板治疗评估 [ADAPT-DES]；NCT00638794）。
