Kucher Nils, Quiroz Rene, McKean Sylvia, Sasahara Arthur A, Goldhaber Samuel Z
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Vasc Med. 2005 Nov;10(4):251-6. doi: 10.1191/1358863x05vm634oa.
We investigated the efficacy and safety of extended enoxaparin monotherapy in symptomatic patients with acute pulmonary embolism (PE). We randomized 40 patients in a 1:1 allocation to enoxaparin monotherapy (1 mg/kg twice daily for 10-18 days, and then 1.5mg/kg once daily until day 90) (n = 20) or to enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin with a target international normalized ratio of 2.0-3.0 for 90 days (at least 10 doses of enoxaparin overlapping with warfarin for at least 4 days) (n = 20). All patients underwent echocardiography, cardiac troponin I (TnI), and brain natriuretic peptide testing to identify patients with an increased likelihood of adverse clinical outcomes. The end-points were newly diagnosed deep venous thrombosis (DVT) or PE and bleeding events through day 90. In 15 patients on extended enoxaparin therapy, we used repeated measure analysis of variance (ANOVA) to investigate differences in anti-Xa levels obtained at 2, 4, 8 and 12 weeks. The patients' mean age was 52 +/- 17 years; the most common comorbidities were obesity (58%), hypertension (30%), concomitant DVT (30%) and cancer (15%). Twelve (30%) patients had elevated cardiac Tnl >0.1 mg/l and 11 (28%) had moderate or severe right ventricular dysfunction on echocardiography. Ten (25%) patients received thrombolysis with a continuous infusion of 100 mg alteplase prior to randomization. During a 90-day follow-up, one patient from the enoxaparin monotherapy group suffered symptomatic distal DVT; one from the warfarin group had recurrent symptomatic PE (p = 1.0). None of the study patients had major hemorrhage; two warfarin group patients had minor bleeding compared with none in the enoxaparin monotherapy group (p = 0.49). Repeated measure ANOVA did not reveal significant differences in anti-Xa levels over time (p = 0.217). In patients with acute symptomatic PE, extended enoxaparin monotherapy is feasible and warrants further investigation in a large clinical trial.
我们研究了延长依诺肝素单药治疗对急性肺栓塞（PE）有症状患者的疗效和安全性。我们将40例患者按1:1比例随机分配，分别接受依诺肝素单药治疗（1mg/kg，每日2次，共10 - 18天，然后1.5mg/kg，每日1次，直至第90天）（n = 20）或接受依诺肝素1.0mg/kg每日2次作为华法林的过渡治疗，目标国际标准化比值为2.0 - 3.0，持续90天（至少10剂依诺肝素与华法林重叠至少4天）（n = 20）。所有患者均接受超声心动图、心肌肌钙蛋白I（TnI）和脑钠肽检测，以识别临床不良结局可能性增加的患者。终点为至第90天新诊断的深静脉血栓形成（DVT）或PE以及出血事件。对于15例接受延长依诺肝素治疗的患者，我们采用重复测量方差分析（ANOVA）来研究在第2、4、8和12周时获得的抗Xa水平的差异。患者的平均年龄为52±17岁；最常见的合并症为肥胖（58%）、高血压（30%）、合并DVT（30%）和癌症（15%）。12例（30%）患者心肌TnI升高>0.1mg/l，11例（28%）患者超声心动图显示有中度或重度右心室功能障碍。10例（25%）患者在随机分组前接受了100mg阿替普酶持续静脉输注溶栓治疗。在90天的随访期间，依诺肝素单药治疗组有1例患者出现有症状的远端DVT；华法林组有1例患者出现复发性有症状的PE（p = 1.0）。研究患者均未发生大出血；华法林组有2例患者出现轻微出血，而依诺肝素单药治疗组无出血发生（p = 0.49）。重复测量ANOVA未显示抗Xa水平随时间有显著差异（p = 0.217）。对于有急性症状的PE患者，延长依诺肝素单药治疗是可行的，值得在大型临床试验中进一步研究。
