Samama M M, Cohen A T, Darmon J Y, Desjardins L, Eldor A, Janbon C, Leizorovicz A, Nguyen H, Olsson C G, Turpie A G, Weisslinger N
Département d'Hématologie Biologique, Hôtel Dieu, Paris, France.
N Engl J Med. 1999 Sep 9;341(11):793-800. doi: 10.1056/NEJM199909093411103.
The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately designed trials.
In a double-blind study, we randomly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin, 20 mg of enoxaparin, or placebo subcutaneously once daily for 6 to 14 days. Most patients were not in an intensive care unit. The primary outcome was venous thromboembolism between days 1 and 14, defined as deep-vein thrombosis detected by bilateral venography (or duplex ultrasonography) between days 6 and 14 (or earlier if clinically indicated) or documented pulmonary embolism. The duration of follow-up was three months.
The primary outcome could be assessed in 866 patients. The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin (5.5 percent [16 of 291 patients]) than in the group that received placebo (14.9 percent [43 of 288 patients]) (relative risk, 0.37; 97.6 percent confidence interval, 0.22 to 0.63; P< 0.001). The benefit observed with 40 mg of enoxaparin was maintained at three months. There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin (43 of 287 patients [15.0 percent]) and the placebo group. The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group. By day 110, 50 patients had died in the placebo group (13.9 percent), 51 had died in the 20-mg group (14.7 percent), and 41 had died in the 40-mg group (11.4 percent); the differences were not significant.
Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses.
在可能存在静脉血栓栓塞风险的急性内科疾病患者中，尚未通过设计充分的试验确定血栓预防的疗效和安全性。
在一项双盲研究中，我们将1102名40岁以上的住院患者随机分为三组，分别接受每日一次皮下注射40毫克依诺肝素、20毫克依诺肝素或安慰剂，疗程为6至14天。大多数患者不在重症监护病房。主要结局是第1天至第14天之间的静脉血栓栓塞，定义为在第6天至第14天（或如有临床指征则更早）通过双侧静脉造影（或双功超声检查）检测到的深静脉血栓形成或记录的肺栓塞。随访期为三个月。
866例患者可评估主要结局。接受40毫克依诺肝素治疗的组中静脉血栓栓塞的发生率（5.5%[291例患者中的16例]）显著低于接受安慰剂治疗的组（14.9%[288例患者中的43例]）（相对风险，0.37；97.6%置信区间，0.22至0.63；P<0.001）。40毫克依诺肝素的疗效在三个月时得以维持。接受20毫克依诺肝素治疗的组（287例患者中的43例[15.0%]）与安慰剂组之间静脉血栓栓塞的发生率无显著差异。安慰剂组与依诺肝素组的不良反应发生率无显著差异。到第110天，安慰剂组有50例患者死亡（13.9%），20毫克组有51例患者死亡（14.7%），40毫克组有41例患者死亡（11.4%）；差异无统计学意义。
每天皮下注射40毫克依诺肝素进行预防性治疗可安全有效地降低急性内科疾病患者静脉血栓栓塞的风险。
