Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors - Results from the CRUSADE (can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) initiative
Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors - Results from the CRUSADE (can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) initiative
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DOI：
10.1161/circulationaha.106.620815
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发表时间：
2006-09-26
期刊：
影响因子：
37.8
通讯作者：
Peterson, Eric D.
中科院分区：
文献类型：
--
作者：
Alexander, Karen P.;Chen, Anita Y.;Peterson, Eric D.
背景--糖蛋白（GP）IIb/IIIa抑制剂对非ST段抬高型急性冠状动脉综合征（NSTE ACS）患者有益;然而，其在女性中的安全使用仍是一个问题。剂量对观察到的性别相关的出血差异的贡献是未知的。方法和结果-我们探讨了患者性别，GP IIb/IIIa抑制剂的使用，剂量和出血之间的关系，在32 601例NSTE ACS患者中，400 CRUSADE不稳定型心绞痛患者的快速危险分层能否通过早期实施ACC/AHA指南抑制不良结局其中18436人接受了治疗。当依替巴肽的肌酐清除率< 50 mL/min或替罗非班的肌酐清除率< 30 mL/min时，GP IIb/IIIa抑制剂剂量被定义为过量（如果没有降低）。大出血定义为红细胞压积下降>= 0.12，需要输血或颅内出血。根据临床因素和抗血栓剂量调整大出血。使用患病率和校正的比值比（OR），按性别确定GP IIb/IIIa剂量过量导致的出血风险。在接受GP IIb/IIIa抑制剂治疗的患者（15.7% vs 7.3%，P < 0.0001）和未接受治疗的患者（8.5% vs 5.4%，P < 0.0001）中，女性的大出血发生率高于男性。尽管血清肌酐水平相似，但接受治疗的女性肌酐清除率平均比男性低20个点。接受治疗的女性也比男性更有可能接受过量的GP IIb/IIIa剂量（46.4% vs 17.2%，P < 0.0001;校正OR 3.81，95%置信区间[CI] 3.39至4.27）。过量给药与女性出血风险增加相关（OR 1.72，95% CI 1.30 - 2.28）和男性（OR 1.27，95% CI 0.97 ~ 1.66）;但是，在此情况下，女性中归因于给药的出血风险要高得多（25.0%对4.4%）。结论--无论是否使用GP IIb/IIIa抑制剂治疗，女性比男性经历更多的出血;然而，由于妇女经常过量用药，多达四分之一的这种与性别有关的出血风险差异是可以避免的。适当的剂量将改善所有NSTE ACS患者的护理，对女性尤其有益。
Background - Glycoprotein (GP) IIb/IIIa inhibitors are beneficial in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); their safe use in women, however, remains a concern. The contribution of dosing to the observed sex-related differences in bleeding is unknown.Methods and Results - We explored the relationship between patient sex, GP IIb/IIIa inhibitor use, dose, and bleeding in 32 601 patients with NSTE ACS across 400 CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) hospitals, of whom 18 436 were treated. GP IIb/IIIa inhibitor dose was defined as excessive if not reduced when creatinine clearance was < 50 mL/min for eptifibatide or < 30 mL/min for tirofiban. Major bleeding was defined as a hematocrit drop >= 0.12, need for transfusion, or intracranial bleeding. Major bleeding was adjusted for clinical factors and antithrombotic dose. The risk for bleeding attributable to excess GP IIb/IIIa dose was determined by sex using prevalence and adjusted odds ratios (ORs). Women had higher rates of major bleeding than men among those treated with GP IIb/IIIa inhibitors (15.7% versus 7.3%, P < 0.0001) and among those not treated (8.5% versus 5.4%, P < 0.0001). Despite similar serum creatinine levels, creatinine clearance averaged 20 points lower among treated women than men. Treated women were also more likely to receive excess GP IIb/IIIa doses than men (46.4% versus 17.2%, P < 0.0001; adjusted OR 3.81, 95% confidence interval [CI] 3.39 to 4.27). Excess dosing was associated with increased risk of bleeding in women (OR 1.72, 95% CI 1.30 to 2.28) and men (OR 1.27, 95% CI 0.97 to 1.66); however, bleeding risk attributable to dosing was much higher in women (25.0% versus 4.4%).Conclusions - Women experience more bleeding than men whether or not they are treated with GP IIb/IIIa inhibitors; however, because of frequent excessive dosing in women, up to one fourth of this sex-related risk difference in bleeding is avoidable. Appropriate dosing will improve care of all patients with NSTE ACS, with a particular benefit for women.