增加氯吡格雷剂量可能降低对氯吡格雷低反应者PCI术后的事件率

Increased Clopidogrel May Lower Events Post-PCI in Low Responders  

（北京安贞医院 苑飞 翻译）

关键点：

• 血管扩张刺激的磷脂酰蛋白指数可能是评估介入术后心脏事件发生风险的有效指标。

PCI前氯吡格雷剂量加倍可能能够安全有效的降低对噻氯吡啶低反应的支架术后患者发生不良事件的风险。

法国马赛Nord大学医院的Laurent Bonello医生在周一指出VASP指数能够指导临床医生将氯吡格雷负荷量增加到2400mg，在不增加出血风险的情况下减少主要不良事件发生率。

Bonello等人进行的研究共随机了162例VASP指数大于50%的患者，在服用初始的600mg氯吡格雷负荷量后，进入治疗组的患者根据需要每24小时接受另外最多3倍于600mg的负荷量，直至VASP指数小于50%，而对照组不给予附加的抗血小板治疗。

在30天时研究者发现在接受附加氯吡格雷治疗的78例患者中没有心血管死亡、支架内血栓或再血管化发生。在对照组中事件风险增加，其中包括2例心血管死亡（2%），4例支架内血栓（5%）和2例再血管化（2%），在84例患者中总事件发生率超过10%（P=0.007）。

另外，每次增加附加氯吡格雷剂量都会减少低反应患者的数量，从49%减少到35%。尽管最终服用了2400mg的氯吡格雷，仍有11例低反应患者。

每组中均有1例患者发生严重TIMI出血事件，在治疗组中有2例发生轻微TIMI出血事件（3%），对照组有3例（4%）。

VASP指导的负荷剂量

一些研究显示VASP指数小于50%对于预测支架内血栓和MACE事件有较高的阴性预测值。

血小板监测证实在低**应用附加的氯吡格雷负荷量是安全的。根据磷脂酰蛋白的水平监测来调节氯吡格雷的负荷量能够在不增加出血风险的前提下减少对氯吡格雷低反应患者30日的MACE事件发生率。

研究同时根据VASP指数将患者分为3组：在600mg氯吡格雷负荷量后VASP指数小于50%的患者为良好反应者；在第一次600mg氯吡格雷负荷量后VASP指数大于50%，但在3次附加负荷量后VASP指数小于50%的患者为低反映者；在服用2400mg氯吡格雷后VASP指数仍大于50%的患者为抵抗者。

3组人群的基线特征并无明显差异，但无**肥胖、糖尿病和/或表现为急性冠脉综合征的患者更多。

公开：

•Bonello医生没有报告任何相关的利益冲突。

（来源：www.tctmd.com）

Increased Clopidogrel May Lower Events Post-PCI in Low Responders 

Key Points:

• VASP index could be useful marker for assessing risk for cardiac events after intervention.

By TCT Daily Staff

Repeated clopidogrel doses prior to PCI may safely and effectively lower the risk of adverse events after stenting in patients who are poor responders to the thienopyridine.

Laurent Bonello, MD, of Hopital Universitaire Nord, Marseille, France, said Monday that use of the vasodilator-stimulated phosphoprotein (VASP) index helped guide clinicians in increasing the loading dose of clopidogrel up to 2,400 mg, which resulted in a decreased rate of major adverse events without increased bleeding rates.

In their study, Bonello and colleagues randomized 162 patients with a VASP index >50% following an initial 600-mg clopidogrel loading dose to a treatment group that received up to three additional 600-mg doses, based on need, every 24 hours until the VASP index was lowered below the 50% threshold, or to a control group that received no additional antiplatelet therapy.

At 30 days, the researchers reported no CV deaths, stent thromboses or revascularizations among the 78 patients receiving additional clopidogrel doses. In the control group, there was an increased risk for any event, which included two cardiovascular deaths (2%), four stent thromboses (5%), and two revascularizations (2%) — a total incident rate of 10% among the 84 patients in that group (P=.007).

In addition, each additional dose of clopidogrel lowered the number of patients with low response from 49% to 35%, Bonello reported. Eleven patients remained low responders despite a 2,400 mg dose of clopidogrel.

There was one major thrombolysis in myocardial infarction (TIMI) event in both groups. Two minor TIMI events (3%) were reported in the increased-loading dose group and three (4%) in the control group.

VASP-guided loading dose

Several studies have associated a VASP index lower than 50% with a high negative predictive value for stent thrombosis and MACE, said Bonello.

"Using an additional clopidogrel loading dose in patients with low response and according to platelet monitoring was safe," Bonello said. "Adjusting the loading dose of clopidogrel according to phosphoprotein monitoring decreases the rate of MACE after 30 days in patients with clopidogrel low response without increasing bleedings," he said.

The study also identified three groups of patients according to VASP index: good responders who achieve a VASP index ,50% after a 600-mg clopidogrel loading dose, low responders who have a VASP index .50% after the first loading dose but who can be sensitized with up to three additional loading doses, and patients who are resistant and do not achieve a VASP index ,50% even with 2,400 mg of clopidogrel.

There was no difference in baseline characteristics, but nonresponders were "often obese, diabetic, and/or presenting with acute coronary syndrome," Bonello said.

Disclosures:

• Dr. Bonello reports no relevant conflicts of interest.