Serebruany Victor L, Glassman Alexander H, Malinin Alex I, Nemeroff Charles B, Musselman Dominique L, van Zyl Louis T, Finkel Mitchell S, Krishnan K Ranga R, Gaffney Michael, Harrison Wilma, Califf Robert M, O'Connor Christopher M
Sinai Center for Thrombosis Research, Johns Hopkins University, Baltimore, MD 21215, USA.
Circulation. 2003 Aug 26;108(8):939-44. doi: 10.1161/01.CIR.0000085163.21752.0A. Epub 2003 Aug 11.
Depression after acute coronary syndromes (ACSs) has been identified as an independent risk factor for subsequent cardiac death. Enhanced platelet activation has been hypothesized to represent 1 of the mechanisms underlying this association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelet activity. Whether treatment of depressed post-ACS patients with SSRIs alters platelet function was not known. Accordingly, we serially assessed the release of established platelet/endothelial biomarkers in patients treated with sertraline vs placebo in the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART).
Plasma samples (baseline, week 6, and week 16) were collected from patients randomized to sertraline (n=28) or placebo (n=36). Anticoagulants, aspirin, and ADP-receptor inhibitors were permitted in this study. Platelet factor 4, beta-thromboglobulin (betaTG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B2, 6-ketoprostaglandin F1a, vascular cell adhesion molecule-1, and E-selectin were measured by ELISA. Treatment with sertraline was associated with substantially less release of platelet/endothelial biomarkers than was treatment with placebo. These differences attained statistical significance for betaTG (P=0.03) at weeks 6 and 16 and for P-selectin (P=0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and betaTG concentrations across the entire treatment period.
Treatment with sertraline in depressed post-ACS patients is associated with reductions in platelet/endothelial activation despite coadministration of widespread antiplatelet regimens including aspirin and clopidogrel. The antiplatelet and endothelium-protective properties of SSRIs might represent an attractive additional advantage in patients with depression and comorbid coronary artery and/or cerebrovascular disease.
急性冠脉综合征（ACS）后的抑郁已被确定为随后心脏死亡的独立危险因素。血小板活化增强被认为是这种关联的潜在机制之一。已知选择性5-羟色胺再摄取抑制剂（SSRI）可抑制血小板活性。ACS后抑郁患者使用SSRI治疗是否会改变血小板功能尚不清楚。因此，在舍曲林抗抑郁心肌梗死随机试验（SADHART）中，我们对接受舍曲林治疗与接受安慰剂治疗的患者，连续评估了既定的血小板/内皮生物标志物的释放情况。
从随机分配至舍曲林组（n = 28）或安慰剂组（n = 36）的患者中采集血浆样本（基线、第6周和第16周）。本研究允许使用抗凝剂、阿司匹林和ADP受体抑制剂。通过酶联免疫吸附测定法检测血小板因子4、β-血小板球蛋白（βTG）、血小板/内皮细胞黏附分子-1、P-选择素、血栓素B2、6-酮前列腺素F1α、血管细胞黏附分子-1和E-选择素。与安慰剂治疗相比，舍曲林治疗导致血小板/内皮生物标志物的释放显著减少。这些差异在第6周和第16周时βTG（P = 0.03）以及在第16周时P-选择素（P = 0.04）达到统计学显著水平。重复测量方差分析显示，在整个治疗期间，舍曲林在降低E-选择素和βTG浓度方面比安慰剂具有显著优势。
ACS后抑郁患者使用舍曲林治疗，尽管同时使用了包括阿司匹林和氯吡格雷在内的广泛抗血小板治疗方案，但仍与血小板/内皮活化的降低相关。SSRI的抗血小板和内皮保护特性可能是合并抑郁症及冠状动脉和/或脑血管疾病患者的一个有吸引力的额外优势。
