Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.
Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.
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与因子XA抑制剂相关的急性大量出血的Andexanet alfa。
DOI：
10.1056/nejmoa1607887
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发表时间：
2016-09-22
期刊：
影响因子：
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通讯作者：
ANNEXA-4 Investigators
中科院分区：
文献类型：
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作者：
Connolly SJ;Milling TJ Jr;Eikelboom JW;Gibson CM;Curnutte JT;Gold A;Bronson MD;Lu G;Conley PB;Verhamme P;Schmidt J;Middeldorp S;Cohen AT;Beyer-Westendorf J;Albaladejo P;Lopez-Sendon J;Goodman S;Leeds J;Wiens BL;Siegal DM;Zotova E;Meeks B;Nakamya J;Lim WT;Crowther M;ANNEXA-4 Investigators
Andexanet alfa（andexanet）是一种重组修饰的人Xa因子诱饵蛋白，已被证明可以逆转健康志愿者对Xa因子的抑制。在这项多中心、前瞻性、开放标签、单组研究中，我们评估了67例在给予Xa因子抑制剂后18小时内发生急性大出血的患者。所有患者均接受了andexanet推注，然后输注2小时。评价患者抗Xa因子活性指标的变化，并评估12小时内的临床止血疗效。所有患者随后随访30天。47例患者的疗效人群的抗Xa因子活性基线值至少为75 ng/ml（或对于接受依诺肝素的患者，≥0.5 IU/ml），并在裁定时证实了出血严重程度。患者的平均年龄为77岁;大多数患者患有严重的心血管疾病。出血主要为胃肠道或颅内出血。从急诊到andexanet推注给药的平均（±SD）时间为4.8±1.8小时。推注给药后，接受利伐沙班的患者中位抗Xa因子活性较基线降低89%（95%置信区间[CI]，58 - 94），接受阿哌沙班的患者中位抗Xa因子活性较基线降低93%（95% CI，87 - 94）。在2小时输注期间，这些水平保持相似。输注结束后4小时，接受利伐沙班的患者抗Xa因子活性相对于基线降低39%，接受阿哌沙班的患者抗Xa因子活性相对于基线降低30%。在andexanet输注后12小时，在疗效分析中，47例患者中有37例的临床止血被裁定为极好或良好（79%; 95% CI，64 - 89）。在30天随访期间，67例患者中有12例（18%）发生血栓事件。根据描述性初步分析，初始推注andexanet并随后输注2小时，可大幅降低与因子Xa抑制剂相关的急性大出血患者的抗因子Xa活性，79%的患者有效止血。（由Portola Pharmaceuticals资助;附件4 ClinicalTrials.gov编号，NCT 02329327。）
Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti–factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti–factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti– factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti–factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti–factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327.)