他汀类药对氯吡格雷抗血小板作用的影响

Impact of statins on dopidogrel platelet inhibition in patients with acute coronary syndrome or stable angina

目的前瞻性评价普伐他汀、氟伐他汀、阿托伐他汀对氯吡格雷抗血小板作用的影响。方法入选连续1015例急性冠状动脉综合征或稳定性心绞痛行冠状动脉造影和（或）支架术患者，分为普伐他汀组（228例）、氟伐他汀组（179例）、阿托伐他汀组（481例）和对照组（127例）。比较各组术后支架内血栓发生率、不同浓度（2、5、10、20μmol）二磷酸腺苷（ADP）诱导的1min（ADP-1）、5min（ADP-5）和最大血小板聚集力（ADP-M）及其影响因素。结果4组患者基础临床情况（除年龄、高血压及冠状动脉造影复查率外）和冠状动脉病变和（或）支架术情况相似，术后支架内血栓发生率（普伐他汀组0．9％、氟伐他汀组1．1％、阿托伐他汀组1．0％、对照组0．8％，P〉0．05）和ADP-1、ADP-5、ADP—M与对照组相比差异均无统计学意义（P均〉0．05）。多因素回归分析显示，年龄（B=0．21，P=0．001）、氯吡格雷总量（B=7．30，P=0．002）及低分子肝素的使用（OR=6．71，P=0．01）是影响氯吡格雷抗血小板作用的独立决定因素。结论普伐他汀、氟伐他汀和阿托伐他汀对氯吡格雷的抗血小板作用无明显影响，而年龄、氯吡格雷总量及低分子肝素使用是决定氯吡格雷抗血小板作用的独立因素。

Objective This prospective registered study was conducted to investigate the impact of statins （pravastatin, fluvastatin, atorvastatin） on clopidogrel platelet inhibition in patients with acute coronary syndrome （ACS） or stable angina. Methods A total of 1015 consecutive patients with ACS or stable angina underwent coronary angiography/percutaneous coronary intervention （PCI） were allocated to pravastatin group （n = 228）, fluvastatin group （n = 179）, atorvastatin group （ n = 481 ） or placebo control group （n = 127）. Baseline characteristics, coronary angiography/ PCI features and acute steat thrombosis, platelet aggregation induced by 2, 5, 10 and 20 μmol adenosine diphosphate （ADP） at 1 minute （ ADP-1 ）, 5 minutes （ADP-5） and maximal platelet aggregation （ADP-M） were compared among groups. Results Baseline and procedural characteristics were comparable among the four groups. Acute stent thrombosis （pravastatin group 0. 9%, fluvastatin group 1.1%, atorvastatin group 1.0% and control group 0. 8%, all P 〉 0. 05）, ADP-1, ADP-5, and ADP-M （all P 〉 0. 05） were also similar among groups. Multivariate liner and ordinal logistic analysis revealed that age （ B = 0. 21, P = 0. 001 ）, dose of clopidogrel （ B = 7.30, P = 0. 002） and use of low-molecular heparin （ OR = 6. 71, P = 0. 01 ） were independent factors for platelet aggregation inhibition efficacy by clopidogrel. Conclusion Inhibition of platelet aggregation with clopidogrel was influenced by age, clopidogrel dose and low-molecular heparin but not by various statin treatments.