Cheng Susan, Morrow David A, Sloan Sarah, Antman Elliott M, Sabatine Marc S
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circulation. 2009 Mar 10;119(9):1195-202. doi: 10.1161/CIRCULATIONAHA.108.814996. Epub 2009 Feb 23.
Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging.
In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low (<1.25 times); and 16.3% were markedly high (> or =2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio [RR(adj)], 1.14 per decade; P=0.001), were female (RR(adj), 1.46; P<0.001), were of lower weight (RR(adj), 1.19 per 10-kg decrease; P<0.001) or had renal dysfunction (RR(adj), 1.08 per 0.2-mg/dL increase in serum creatinine; P=0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P=0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P=0.057).
Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy.
尽管基于体重的列线图已提高了非普通肝素在ST段抬高型心肌梗死中的给药疗效和安全性，但在实际应用中实现治疗性抗凝仍具有挑战性。
在急性心肌梗死再灌注治疗中依诺肝素与溶栓治疗-心肌梗死溶栓试验（ExTRACT-TIMI）25研究中，20506例ST段抬高型心肌梗死患者被随机分为依诺肝素组或非普通肝素组，后者根据美国心脏病学会/美国心脏协会基于体重的列线图给药，并进行中心监测活化部分凝血活酶时间（aPTT）。共有6055例患者接受了研究用非普通肝素和纤维蛋白特异性溶栓剂治疗，并在开始治疗后4至8小时内首次检测aPTT。尽管严格遵循推荐剂量，但仅33.8%的首次aPTT达到治疗水平（为对照值的1.50至2.00倍）；13.2%显著低于治疗水平（<对照值的1.25倍）；16.3%显著高于治疗水平（≥对照值的2.75倍）。显著高于治疗水平的aPTT在年龄较大的患者中更常见（校正风险比[RR(adj)]，每增加十岁为1.14；P=0.001）、女性患者中更常见（RR(adj)，1.46；P<0.001）、体重较低的患者中更常见（RR(adj)，每降低10 kg为1.19；P<0.001）或有肾功能不全的患者中更常见（RR(adj)，血清肌酐每增加0.2 mg/dL为1.08；P=0.006）。显著高于治疗水平的aPTT与48小时内TIMI主要或轻微出血风险增加相关（比值比，2.11；P=0.004）；显著低于治疗水平的aPTT往往与48小时内致命或非致命再梗死风险增加相关（比值比，2.19；P=0.057）。
尽管在ST段抬高型心肌梗死中使用了标准的基于体重的非普通肝素列线图，但非治疗性抗凝仍很常见，且在某些易感患者群体中更易出现，抗凝过度与出血增加相关，抗凝不足与再梗死相关。在给予非普通肝素以支持溶栓治疗时应考虑这些发现。
