LaPointe Nancy M Allen, Chen Anita Y, Alexander Karen P, Roe Matthew T, Pollack Charles V, Lytle Barbara L, Ohman Magnus E, Gibler Brian W, Peterson Eric D
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA.
Arch Intern Med. 2007 Jul 23;167(14):1539-44. doi: 10.1001/archinte.167.14.1539.
The efficacy of enoxaparin sodium in non-ST-segment elevation acute coronary syndromes is well established; however, concerns remain regarding bleeding risk. The extent to which bleeding risk is attributable to excess dosing of enoxaparin is unclear.
Using data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) National Quality Improvement Initiative, we determined the frequency of administration of excess (>10 mg above the recommended dose), lower-than-recommended (>10 mg below the recommended dose), and recommended doses of enoxaparin. We also determined unadjusted and adjusted risks of in-hospital major bleeding and death associated with excess and lower-than-recommended doses of enoxaparin.
Of 10 687 patients, 2002 (18.7%) received an excess dose and 3116 (29.2%) received a lower-than-recommended dose of enoxaparin. Patients receiving excess doses were older (median age, 78 vs 66 years), smaller (median body mass index [calculated as weight in kilograms divided by height in meters squared], 26.2 vs 27.8), and more likely to be female (59.5% vs 38.2%) than patients receiving recommended doses (P < .001 for all). After adjustment for baseline characteristics, an excess dose was significantly associated with major bleeding (odds ratio, 1.43; 95% confidence interval [CI], 1.18-1.75) and death (odds ratio, 1.35; 95% CI, 1.03-1.77) compared with a recommended dose. A lower-than-recommended dose was not associated with major bleeding (odds ratio, 1.01; 95% CI, 0.84-1.21), but there was a trend toward higher mortality (odds ratio, 1.25; 95% CI, 0.93-1.68).
Almost half the patients treated with enoxaparin did not receive a recommended dose and had worse outcomes, especially those receiving an excess dose. Improved adherence to the recommended dose could substantially improve the safety profile of enoxaparin.
依诺肝素钠在非ST段抬高型急性冠状动脉综合征中的疗效已得到充分证实；然而，对于出血风险仍存在担忧。依诺肝素过量给药导致出血风险的程度尚不清楚。
利用CRUSADE（不稳定型心绞痛患者能否通过早期实施ACC/AHA指南抑制不良结局的快速风险分层）国家质量改进计划的数据，我们确定了依诺肝素过量给药（超过推荐剂量10 mg以上）、低于推荐剂量（低于推荐剂量10 mg以下）和推荐剂量的给药频率。我们还确定了与依诺肝素过量和低于推荐剂量相关的住院期间大出血和死亡的未调整和调整风险。
在10687例患者中，2002例（18.7%）接受了过量剂量的依诺肝素，3116例（29.2%）接受了低于推荐剂量的依诺肝素。与接受推荐剂量的患者相比，接受过量剂量的患者年龄更大（中位年龄，78岁对66岁）、体型更小（中位体重指数[计算方法为体重千克数除以身高米数的平方]，26.2对27.8），且女性比例更高（59.5%对38.2%）（所有P<0.001）。在对基线特征进行调整后，与推荐剂量相比，过量剂量与大出血（比值比，1.43；95%置信区间[CI]，1.18-1.75）和死亡（比值比，1.35；95%CI，1.03-1.77）显著相关。低于推荐剂量与大出血无关（比值比，1.01；95%CI，0.84-1.21），但有死亡率升高的趋势（比值比，1.25；95%CI，0.93-1.68）。
接受依诺肝素治疗的患者中近一半未接受推荐剂量，且结局较差，尤其是接受过量剂量的患者。提高对推荐剂量的依从性可显著改善依诺肝素的安全性。
