目的 探索人工瓣膜术后患者华法林的出血不良事件及其影响因素,为真实世界华法林安全使用提供指导。方法 采用回顾性分析的方法收集近5年来中国医学科学院阜外医院心脏外科因人工心脏瓣膜置换手术而服用华法林至少3个月的患者的相关临床信息。结果 共纳入412例患者,其中39例(9.5%)患者发生了62例次出血事件。仅有3例发生大出血,其余均为非大出血。倾向性评分匹配前后,两组患者的年龄、身高、体重、身体质量指数(body mass index,BMI)、性别、合并疾病和合并用药方面无显著性差异,出血组国际标准化比值(internation normailzed ratio,INR)在治疗范围内时间的百分比(time in therapy range,TTR)显著高于非出血组(匹配前P=0.023,匹配后P=0.008),但INR在治疗范围内次数的百分比(percentage of INR determinations in range,PINNR)无显著差异。出血组患者INR>3的情况为4例次,平均INR值<3。除了鼻出血事件在术后第1个月发生率较高外,其他事件在术后前3个月的分布无明显差异。结论 人工瓣膜术后华法林抗凝治疗绝大多数为非大出血事件,应为患者宣教诊疗相关基础疾病和纠正可逆转的出血风险因素的重要性。抗凝门诊可改善患者的TTR,但当INRs监测时间间隔不同时,TTRs是否能够反应真实的华法林抗凝质量应当存疑,尤其是间隔时间较短可能高估TTR值,此时选择PINNR更为合理。
Abstract
OBJECTIVE To explore the bleeding events associated with warfarin and its influence factors in patients with prosthetic heart valves and provide guidance for clinical practice in real world setting. METHODS Clinical data on patients with warfarin after prosthetic heart valves were collected retrospectively. RESULTS Of 412 eligible patients, 39 (9.5%) patents had 62 bleeding events. Only 3 patients suffered from major bleeding, while the others had non-major bleeding. Before and after matching, there were no significant differences in age, height, weight, BMI, gender, combined diseases and combined medication between the two groups, and the time in therapy range (TTR) in bleeding group was significantly longer than that in non-bleeding group (before matching P=0.023, after matching P=0.008), but there was no significant difference in percentage of INR determinations in range (PINNR). In bleeding group, INR>3 was found in 4 cases, and the average INR value was below 3. There was no significant difference in the distribution of non-major bleeding events in the first 3 months, except for the higher incidence of epistaxis in the first month after surgery. CONCLUSION The majority of bleeding events in patients on warfarin after prosthetic valve surgery is non-major bleeding events. It is important to educate patients about the underlying diseases related to diagnosis and treatment and to correct reversible bleeding risk factors. Anticoagulation clinic is able to improve TTR. However, it is doubtful whether TTR can reflect the true quality of warfarin anticoagulation when INR monitoring time interval varies greatly, especially short interval time may lead to overestimation of TTR, and PINNR makes more sense in this situation.
关键词
华法林 /
出血事件 /
抗凝质量 /
人工心脏瓣膜
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Key words
warfarin /
bleeding event /
anticoagulation quality /
heart valve prosthesis
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中图分类号：
R973
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参考文献
[1] MARCATTO L R, SACILOTTO L, BUENO C T, et al. Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range-study protocol for a randomized controlled trial[J]. BMC Cardiovasc Disord, 2016, 16(1):224. Doi:10.1186/s12872-016-0405-1.
[2] SCHULMAN S, ANGERAS U, BERGQVIST D, et al. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients[J]. J Thromb Haemost, 2010, 8(1):202-204.
[3] Expert Committee of Chinese Guidelines for the Prevention and Treatment of Thrombotic Diseases. Guidelines for prevention and treatment of thrombotic diseases in china[J]. Natl Med J China(中华医学杂志), 2018, 98(36):2861-2888.
[4] ROSENDAAL F R, CANNEGIETER S C, VAN DER MEER F J, et al. A method to determine the optimal intensity of oral anticoagulant therapy[J]. Thromb Haemost, 1993, 69(3):236-239.
[5] VERHOEF T I, REDEKOP W K, LANGENSKIOLD S, et al. Cost-effectiveness of pharmacogenetic-guided dosing of warfarin in the united kingdom and sweden[J]. Pharmacogenom J, 2016, 16(5):478-484.
[6] OKUYAMA Y, MATSUO M, MATSUO H, et al. Introduction of point-of-care testing in japanese outpatient clinics is associated with improvement in time in therapeutic range in anticoagulant-treated patients[J]. Circ J, 2014, 78(6):1342-1348.
[7] DING Z, PAN W F, SHA L, et al. A real world study on warfarin anticoagulation therapy after prosthetic valve surgery-a retrospective analysis of five years' data from the anticoagulation clinic of our hospital[J]. Chin Pharm J(中国药学杂志), 2020, 55(20):1722-1725.
[8] CONNOLLY S J, EZEKOWITZ M D, YUSUF S, et al. Dabigatran versus warfarin in patients with atrial fibrillation[J]. N Engl J Med, 2009, 361(12):1139-1151.
[9] PATEL M R, MAHAFFEY K W, GARG J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation[J]. N Engl J Med, 2011, 365(10):883-891.
[10] GRANGER C B, ALEXANDER J H, MCMURRAY J J, et al. Apixaban versus warfarin in patients with atrial fibrillation[J]. N Engl J Med, 2011, 365(11):981-992.
[11] GIUGLIANO R P, RUFF C T, BRAUNWALD E, et al. Edoxaban versus warfarin in patients with atrial fibrillation[J]. N Engl J Med, 2013, 369(22):2093-2104.
[12] REIFFEL J A. Time in the therapeutic range for patients taking warfarin in clinical trials:useful, but also misleading, misused, and overinterpreted[J]. Circulation, 2017, 135(16):1475-1477.
[13] HE F B, JIANG D N, YAO L. Blood coagulation changes of heart valve prostheses patients and monitoring of bleeding side effects of warfarin[J]. Med J West China(西部医学), 2016, 28(1):113-115.
[14] AN S H, LEE K E, CHANG B C, et al. Association of gene polymorphisms with the risk of warfarin bleeding complications at therapeutic inr in patients with mechanical cardiac valves[J]. J Clin Pharm Ther, 2014, 39(3):314-318.
[15] SIDDIQUI S, DEREMER C E, WALLER J L, et al. Variability in the calculation of time in therapeutic range for the quality control measurement of warfarin[J]. J Innov Card Rhythm Manag, 2018, 9(12):3428-3434.
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脚注
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基金
首都临床特色应用研究与成果推广项目资助(Z171100001017216);中国毒理学会临床毒理专项资助(CST2021CT103);北京医卫健康公益基金会医学科学研究基金项目资助(B17248-047);2022年度慢性病防治与健康教育科研项目资助(BJMB0012022028006)
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