Avalon Juan Carlo, Fuqua Jacob, Miller Tyler, Deskins Seth, Wakefield Chelby, King Austin, Inderbitzin-Brooks Sonya, Bianco Christopher, Veltri Lauren, Fang Wei, Craig Michael, Kanate Abraham, Ross Kelly, Malla Midhun, Patel Brijesh
West Virginia University School of Medicine, Morgantown, USA.
West Virginia University Heart and Vascular Institute, Morgantown, WV, 26506, USA.
Cardiooncology. 2021 Nov 19;7(1):38. doi: 10.1186/s40959-021-00125-8.
Ibrutinib is a Bruton's tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown.
This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD.
A single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. The predictors of atrial arrhythmia (namely atrial fibrillation) were assessed using logistic regression. A Cox-Proportional Hazard model was created for mortality.
Patients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. There were no differences in risk of bleeding or discontinuation between the two cohorts.
Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.
伊布替尼是一种用于治疗血液系统恶性肿瘤的布鲁顿酪氨酸激酶抑制剂。与伊布替尼相关的最常见心脏毒性是房性心律失常（心房颤动和心房扑动）。已知心血管疾病（CVD）患者发生房性心律失常的风险增加。然而，预先存在CVD的患者接受伊布替尼治疗时房性心律失常的发生率尚不清楚。
本研究探讨与无既往CVD的患者相比，预先存在CVD的患者发生房性心律失常的风险是否更高。
对2012年至2020年接受伊布替尼治疗且无房性心律失常既往史的患者进行单机构回顾性病历审查。患者被分为两个队列：患有CVD的患者（已知有冠状动脉疾病、心力衰竭、肺动脉高压、至少中度瓣膜性心脏病或器械植入史）和无CVD的患者。主要结局是房性心律失常的发生率，次要结局是全因死亡率、出血风险和伊布替尼停药情况。使用逻辑回归评估房性心律失常（即心房颤动）的预测因素。建立Cox比例风险模型用于死亡率分析。
患者的中位随访时间为1.1年。在217例接受伊布替尼治疗的患者中，CVD队列中新发房性心律失常的发生率比无CVD队列高近三倍（17%对7%，p = 0.02）。与无CVD的患者相比，CVD患者在随访期间调整后的全因死亡率也有所增加（OR 1.9，95%CI 1.06 - 3.41，p = 0.01），生存概率降低（43%对54%，p = 0.04）。两个队列之间在出血风险或停药方面没有差异。
预先存在的心血管疾病与接受伊布替尼治疗的血液系统恶性肿瘤患者房性心律失常和死亡率显著升高相关。
