Comprehensive safety analysis of concomitant drotrecogin alfa (activated) and prophylactic heparin use in patients with severe sepsis

被引:11
作者
Levy, Mitchell [1 ,2 ]
Levi, Marcel [3 ,4 ]
Williams, Mark D. [5 ]
Antonelli, Massimo [6 ]
Wang, Dazhe [5 ]
Mignini, Mariano Alejandro [7 ]
机构
[1] Rhode Isl Hosp, Providence, RI 02903 USA
[2] Brown Univ, Sch Med, Providence, RI 02903 USA
[3] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1105 AZ Amsterdam, Netherlands
[5] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA
[6] Univ Cattolica Sacro Cuore, Policlin Univ A Gemelli, Rome, Italy
[7] Eli Lilly SpA, Dept Med, Sesto Fiorentino, Italy
关键词
Severe sepsis; Drotrecogin alfa (activated); Heparin; XPRESS; Clinical trial; Recombinant human activated protein C; ACUTE CORONARY SYNDROMES; THROMBIN GENERATION; UNSTABLE ANGINA; PROTEIN-C; DISCONTINUATION; CESSATION; RISK; THROMBOCYTOPENIA; EFFICACY; THERAPY;
D O I
10.1007/s00134-009-1483-7
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
The safety of using heparin concomitantly with drotrecogin alfa (activated) {DrotAA} was explored in the XPRESS study. No heparin effect on mortality was observed. Safety results from that study are explored in more detail. A randomized, double-blind trial of prophylactic heparin versus placebo in severe sepsis patients treated with DrotAA (24 mu g/(kg h) for 96 h) was conducted at 224 sites in 20 countries. Patients were randomized 1:1:2 to receive unfractionated heparin (UFH) (5,000 Units twice daily) (n = 511), low-molecular-weight heparin (LMWH) (enoxaparin, 40 mg per day) (n = 493), or placebo (n = 990) every 12 h during the DrotAA infusion. Bleeding events during the DrotAA infusion period (Days 0-6) were higher in the heparin than placebo groups (10.8 vs. 8.1%; p = 0.049), but serious bleeding events were similar (heparin 2.3% vs. placebo 2.5%; p = 0.72) and central nervous system (CNS) bleeds were rare in both groups (0.3 vs. 0.3%). Fewer heparin patients experienced an ischemic stroke during infusion (0.3 vs. 1.3%; p = 0.018) and 28-day period (0.5 vs. 1.8%; p = 0.009). Coadministration of DrotAA with low-dose heparin in severe sepsis patients did not increase incidence of serious bleeding. Fewer ischemic strokes in the heparin group suggest heparin cessation should be avoided during DrotAA infusion.
引用
收藏
页码:1196 / 1203
页数:8
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