Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes
Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes
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DOI：
10.1001/jama.294.24.3108
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发表时间：
2005-12-28
影响因子：
120.7
通讯作者：
Peterson, ED
中科院分区：
文献类型：
--
作者：
Alexander, KP;Chen, AY;Peterson, ED
研究背景有效的医疗保健需要将循证医学的药物以与研究剂量相当的剂量提供给适当的患者。目的研究普通肝素（UFH）、低分子量肝素（LMWH）和糖蛋白IIb/IIIa抑制剂的剂量，以及剂量与主要结局之间的关系。和参与者对美国387家学术和非学术医院的30136名CRUSADE患者进行了前瞻性观察分析不稳定型心绞痛患者的快速风险分层能否通过早期实施美国心脏病学会/美国心脏协会指南抑制不良结局非ST段抬高型急性冠状动脉综合征患者的国家质量改进计划登记研究2004年1月1日至9月30日期间，有胸痛和阳性心电图或心脏生物标志物的非ST段抬高型急性冠脉综合征（NSTE ACS）患者。和糖蛋白IIb/ IIIa抑制剂和主要的临床结果，包括出血，住院死亡率，和longs.Results共3354例（42%）与NSTE ACS谁是管理抗血栓药物接受至少1个初始剂量超出推荐范围。2934例（32.8%）接受UFH治疗的患者、1378例（13.8%）接受LMWH治疗的患者和2784例（26.8%）接受糖蛋白IIb/IIIa抑制剂治疗的患者接受过量给药。与过量给药相关的因素包括年龄较大、女性、肾功能不全、低体重、糖尿病和充血性心力衰竭。相对于未过量使用UFH、LMWH和糖蛋白IIb/IIa抑制剂的患者，过量使用UFH、LMWH和糖蛋白IIb/IIa抑制剂的患者倾向于大出血或大出血风险较高（校正比值比[OR]，1.08; 95%置信区间[CI]，0.94-1.26; OR，1.39; 95% CI，1.11-1.74; OR，1.36; 95% CI，1.10-1.68）。出血增加与过量剂量的程度和过量给药的药物数量相关（如果肝素和糖蛋白IIb/IIIa均不过量，则为6.6% [237/3590]，如果两者均过量，则为22.2% [93/419]）。过量给药患者的死亡率和住院时间也较高。我们估计，15%（400/2766）的大出血，在这一人群中可能是由于过量dosing.Conclusions NSTE ACS患者在社区治疗往往会收到过量的抗血栓治疗。给药错误更常发生在脆弱人群中，并预测大出血的风险增加。
Context Effective medical care assumes delivery of evidence-based medicines to appropriate patients with doses comparable to those studied.Objective To investigate dosing of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and glycoprotein IIb/IIIa inhibitors, and the association between dosing and major outcomes.Design, Setting, and Participants A prospective observational analysis in 387 US academic and nonacademic hospitals of 30136 patients from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative Registry who had non-ST-segment elevation acute coronary syndromes (NSTE ACS) with chest pain and either positive electrocardiograms or cardiac biomarkers between January 1 and September 30, 2004.Main Outcome Measures Excessive dosing of UFH, LMWH, and glycoprotein IIb/ IIIa inhibitors and major clinical outcomes, including bleeding, in-hospital mortality, and length of stay.Results A total of 3354 patients (42%) with NSTE ACS who were administered antithrombotic agents received at least 1 initial dose outside the recommended range. An excess dose was administered to 2934 patients (32.8%) treated with UFH, 1378 (13.8%) treated with LMWH, and 2784 (26.8%) treated with glycoprotein IIb/IIIa inhibitors. Factors associated with excess dosing included older age, as well as female sex, renal insufficiency, low body weight, diabetes mellitus, and congestive heart failure. Relative to those patients not administered excess dosages, patients with excess dosages of UFH, LMWH, and glycoprotein IIb/IIa inhibitors either tended toward or had higher risks for major bleeding (adjusted odds ratio [OR], 1.08; 95% confidence interval [CI], 0.94-1.26; OR, 1.39; 95% Cl, 1.11-1.74; and OR, 1.36; 95% Cl, 1.10-1.68; respectively). Bleeding increased relative to the degree of excess dose and to the number of agents administered in excess (6.6% [237/3590] if neither heparin nor glycoprotein IIb/IIIa excess vs 22.2% [93/419] if both excess). Mortality and length of stay were also higher among those patients administered excess dosing. We estimated that 15% (400/2766) of major bleeding in this population may be attributable to excess dosing.Conclusions Patients with NSTE ACS treated in the community often receive excess doses of antithrombotic therapy. Dosing errors occur more often in vulnerable populations and predict an increased risk of major bleeding.