Sahebkar Amirhossein, Catena Cristiana, Ray Kausik K, Vallejo-Vaz Antonio J, Reiner Željko, Sechi Leonardo A, Colussi GianLuca
GianLuca Colussi, MD, Clinica Medica, University of Udine, University Hospital, Building 8, 1st floor, 33100 Udine, Italy, Tel.: +39 0432 559 804, Fax: +39 0432 559 490, E-mail:
Thromb Haemost. 2016 Jul 4;116(1):162-71. doi: 10.1160/TH15-10-0770. Epub 2016 Mar 24.
Elevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I² test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and "trim and fill" tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: -15.72 ng/ml, 95 % confidence interval [CI]: -25.01, -6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: -21.32 ng/ml, 95 % CI: -32.73, -9.91, I²=99 %) and particularly atorvastatin (WMD: -20.88 ng/mL, 95 % CI: -28.79, -12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations.
促血栓形成和促炎因子纤溶酶原激活物抑制剂-1（PAI-1）的血浆水平升高可能会促使动脉粥样硬化性心血管疾病的发病。除了其降脂作用外，他汀类药物已被证明可调节血浆PAI-1水平，但来自个别随机对照试验（RCT）的证据存在争议。因此，我们旨在通过对RCT进行荟萃分析来评估他汀类药物治疗对血浆PAI-1浓度的潜在影响。我们检索了Medline和SCOPUS数据库（截至2014年10月3日），以确定研究他汀类药物治疗对血浆PAI-1浓度影响的RCT。我们进行了随机效应荟萃分析，并评估了异质性（I²检验、亚组分析和敏感性分析）以及发表偏倚（漏斗图、Egger检验和“修剪填充”检验）。纳入了16项RCT（包括19个治疗组），汇总分析显示他汀类药物在降低血浆PAI-1浓度方面有显著效果（加权平均差WMD：-15.72 ng/ml，95%置信区间[CI]：-25.01，-6.43）。在亚组分析中，这种效应在亲脂性他汀类药物（阿托伐他汀和辛伐他汀）中仍然显著（WMD：-21.32 ng/ml，95% CI：-32.73，-9.91，I²=99%），尤其是阿托伐他汀（WMD：-20.88 ng/mL，95% CI：-28.79，-12.97，I²=97%）。在荟萃回归分析中，他汀类药物对PAI-1的影响与给药剂量、治疗持续时间以及血浆低密度脂蛋白胆固醇浓度的变化无关。最后，观察到了发表偏倚的证据。总之，考虑到研究之间异质性的局限性，本荟萃分析表明他汀类药物治疗（主要是阿托伐他汀）可显著降低血浆PAI-1浓度。
