Management of Atrial Fibrillation ism Patients on Ibrutinib: A Cleveland Clinic Experience
Management of Atrial Fibrillation ism Patients on Ibrutinib: A Cleveland Clinic Experience
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DOI：
10.7759/cureus.2701
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发表时间：
2018-05-01
影响因子：
1.2
通讯作者：
Daw, Hamed
中科院分区：
文献类型：
--
作者：
Khalid, Sidra;Yasar, Samin;Daw, Hamed
伊布鲁替尼是一种Bruton氏酪氨酸激酶抑制剂，美国食品和药物管理局(FDA)批准其用于治疗慢性淋巴细胞白血病、套细胞淋巴瘤和Waldenstrom‘s巨球蛋白血症。伊布鲁替尼与房颤和出血事件有关。我们的目的是确定在开始使用伊布鲁替尼时既有房颤的处理方法，以及伊布鲁替尼诱导的房颤的处理方法。我们的重点是使用哪些心率和节律控制策略以及关于使用抗血小板和抗凝剂的决定。材料和方法我们对2014年2月至2017年2月的三年期间的病例记录进行了回顾性描述性研究。我们回顾了克利夫兰诊所数据库中的597份病历。43名患者开始使用伊布鲁替尼。在这些患者中，10人在服用伊布鲁替尼之前有心房颤动，4人在服用伊布鲁替尼时发生了心房颤动。收集的数据包括人口学细节、合并症、CHA(2)DS(2)-VASc(充血性心力衰竭、高血压、年龄、糖尿病、既往中风、短暂性脑缺血发作或血栓栓塞症、血管疾病、年龄和性别类别)、出血(高血压、肾和肝功能异常、中风、出血、不稳定的INR、老年人和药物或酒精)以及用于抗血小板作用、用于抗凝、用于心率和节律控制的药物。结果43例患者中，14例(32.5%)发生或发展为心房颤动，10例(23.26%)既往有心房颤动，4例(9.30%)在使用伊布鲁替尼后发生心房颤动。大多数是男性(71.42%)和高加索人(71.42%)。疾病构成依次为慢性淋巴细胞白血病(42.86%)、套细胞淋巴瘤(50%)、Waldenstrom巨球蛋白血症(7.14%)。有心房颤动史的患者平均起始量为569 mg，发生心房颤动的患者平均起始量为420 mg。在伊布鲁替尼之前有心房颤动的10名患者中，所有10名患者都在服用β受体阻滞剂，1名服用地尔硫卓，3名服用胺碘酮，1名服用氟卡胺，1名服用地高辛，还有1名服用Tikosyn(R)(辉瑞公司，纽约，纽约)。两名患者的伊布鲁替尼剂量减少或停用。在服用伊布鲁替尼后出现心房颤动的患者中，3人服用β受体阻滞剂，2人服用胺碘酮，1人服用替可辛。有一名患者停用了伊布鲁替尼。在既往有心房颤动的患者中，3人服用华法林，1人服用依诺肝素，2人服用阿匹沙班。在三名患者中，阿司匹林和依诺肝素停用。在开始服用伊布鲁替尼后出现心房颤动的患者，两人服用依诺肝素，一人服用阿皮沙班。所有患者均未发生中风、短暂性脑缺血发作(TIA)或出血事件。结论从我们的研究中可以得出结论，伊布鲁替尼可以安全地用于房颤，而当房颤发生时，我们进一步得出结论，β受体阻滞剂是控制心率的首选药物。伊布鲁替尼与其他心率和节律控制剂有许多药物相互作用；因此，它们的使用量较低。当心房颤动失控时，伊布鲁替尼被暂时控制，然后谨慎地重新启动。是否开始或调整抗凝取决于医生评估的出血和中风风险。
BackgroundIbrutinib is a Bruton's tyrosine kinase inhibitor, which is United States Food and Drug Administration (FDA)-approved for chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Ibrutinib is associated with atrial fibrillation and bleeding events. Our aim is to determine the management of prior atrial fibrillation when starting ibrutinib, as well as ibrutinib-induced atrial fibrillation. Our focus is on which rate and rhythm control strategies to use and decisions regarding the use of antiplatelet and anticoagulation agents.Materials and MethodsWe conducted a retrospective descriptive study of case records over a three-year period from February 2014 to February 2017. We reviewed 597 patient charts from the Cleveland Clinic database. Ibrutinib was started in 43 patients. Of those, 10 had atrial fibrillation prior to starting ibrutinib and four developed atrial fibrillation while on ibrutinib. Data was collected for demographic details, co-morbid conditions, CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke, transient ischemic attack or thromboembolism, vascular disease, age, and sex category) score, HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, and drugs or alcohol) score, and drugs used for antiplatelet effects, for anticoagulation, and for rate and rhythm control. Outcomes for embolic and bleeding events were assessed.ResultsOf the 43 patients, 14 (32.5%) had or developed atrial fibrillation; 10 (23.26%) had prior atrial fibrillation, and four (9.30%) developed atrial fibrillation after starting ibrutinib. The majority were males (71.42%) and Caucasian (71.42%). The disease breakdown was chronic lymphocytic leukemia (42.86%), mantle cell lymphoma (50%), and Waldenstrom's macroglobulinemia (7.14%). The mean starting dose of ibrutinib in patients with prior atrial fibrillation was 569 mg and for patients who developed atrial fibrillation was 420 mg. In the 10 patients who had atrial fibrillation prior to ibrutinib, all 10 were on beta blockers, one was on diltiazem, three were on amiodarone, one was on flecainide, one was on digoxin, and one was on Tikosyn (R) (Pfizer, Inc., New York, NY). The ibrutinib dose was decreased/discontinued in two patients. In patients who developed atrial fibrillation after starting ibrutinib, three were on beta blockers, two on amiodarone, and one on Tikosyn. Ibrutinib was discontinued in one patient. In patients who had prior atrial fibrillation, three were on warfarin, one on enoxaparin, and two on apixaban. In three patients, aspirin and enoxaparin were discontinued. In patients who developed atrial fibrillation after starting ibrutinib, enoxaparin was given to two and apixaban to one. None of the patients had a stroke, transient ischemic attack (TIA), or bleeding events.ConclusionsFrom our study, we concluded that ibrutinib can be safely given in the presence of atrial fibrillation, and when atrial fibrillation was induced, we further concluded that beta blockers were the preferred agents for rate control. Ibrutinib has many drug interactions with other rate and rhythm control agents; hence, their use was lower. When atrial fibrillation was uncontrolled, ibrutinib was temporarily held and then cautiously restarted. The decision to start or adjust anticoagulation depended on the bleeding and stroke risks as assessed by their physicians.