Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events - The Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) platelet substudy
Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events - The Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) platelet substudy
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DOI：
10.1161/01.cir.0000085163.21752.0a
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发表时间：
2003-08-26
期刊：
影响因子：
37.8
通讯作者：
O'Connor, CM
中科院分区：
文献类型：
--
作者：
Serebruany, VL;Glassman, AH;O'Connor, CM
背景-急性冠脉综合征（ACS）后抑郁已被确定为随后心源性死亡的独立危险因素。血小板活化增强被假设为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）抑制血小板活性。目前尚不清楚用SSRIs治疗ACS后抑郁患者是否会改变血小板功能。因此，我们在舍曲林抗抑郁剂心脏病发作随机试验（SADHART）中连续评估了舍曲林与安慰剂治疗患者中已建立的血小板/内皮生物标志物的释放。方法和结果-从随机分配至舍曲林（n = 28）或安慰剂（n = 36）的患者中收集血浆样本（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ELISA测定血小板因子4、β-血小板球蛋白（β TG）、血小板/内皮细胞粘附分子-1、P-选择素、血栓烷B-2、6-酮前列腺素F-1 a、血管细胞粘附分子-1和E-选择素。与安慰剂相比，舍曲林治疗与血小板/内皮生物标志物的释放显著减少相关。这些差异在第6周和第16周的β TG（P = 0.03）和第16周的P-选择素（P = 0.04）达到统计学显著性。重复测量方差分析显示，舍曲林与安慰剂减少E-选择素和betaTG浓度在整个treatment period.Conclusions的显着优势-治疗与舍曲林抑郁后ACS患者与血小板/内皮细胞活化减少，尽管共同管理广泛的抗血小板治疗方案，包括阿司匹林和氯吡格雷。SSRIs的抗血小板和内皮保护特性可能是抑郁症和共病冠状动脉和/或脑血管疾病患者的一个有吸引力的额外优势。
Background - 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).Methods and Results - 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 B-2, 6-ketoprostaglandin F-1a, 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.Conclusions - 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.