Ibrutinib is associated with dramatic efficacy against B-cell malignancies. Yet, ibrutinib is linked with potentially-limiting cardiotoxicity, including emerging reports of profound hypertension. However, the long-term incidence, severity, and impacts of hypertension development during ibrutinib-use are unknown. Therefore, from 562 consecutive patients treated with ibrutinib for B-cell malignancies between 2009-2016 we assessed the incidence of new/incident or worsened hypertension [systolic blood pressure (BP) cutoff of 130mmHg]. Observed incident-hypertension rates were compared to Framingham-heart predicted incident-hypertension rates. We also evaluated the relationship of hypertension on ibrutinib to the development of other major-adverse-cardiovascular-events (MACE), including arrhythmias, myocardial infarction, stroke, heart failure, and cardiovascular death. Further, we assessed the preventative and modulatory effects of antihypertensives, by medication-class, on ibrutinib-related hypertension. Overall, 78.3% of ibrutinib-users developed new or worsened hypertension [mean systolic BP increase 5.2mmHg ({plus minus}20.7)] over a median of 30months. New hypertension developed in 71.6% of ibrutinib-users (467 observed vs. 39 Framingham-predicted cases per 1,000 person-years), with a time-to-50% cumulative incidence of 4.2months. Among those without preceding hypertension, 17.7% developed high-grade (BP >160/100mmHg) hypertension. In multivariable regression containing known predictors of MACE, new or worsened hypertension was associated with increased MACE [hazard ratio (HR) 2.17, 95%CI 1.08-4.38]. No single-antihypertensive class was associated with prevention or control of ibrutinib-related hypertension. However, antihypertensive initiation was associated with a lower risk of MACE (HR 0.40, CI 0.24-0.66). Collectively, these data suggest ibrutinib is associated with substantial increase in the incidence and severity of hypertension, and that hypertension development may suggest a higher risk of subsequent cardiotoxic events.

中文翻译：

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依鲁替尼开始治疗后的高血压和心血管事件

依鲁替尼对 B 细胞恶性肿瘤具有显着疗效。然而，依鲁替尼与潜在限制性心脏毒性有关，包括新出现的严重高血压报告。然而，伊布替尼使用期间高血压发展的长期发病率、严重程度和影响尚不清楚。因此，从 2009 年至 2016 年间接受依鲁替尼治疗 B 细胞恶性肿瘤的 562 名连续患者中，我们评估了新发/发生或恶化的高血压的发生率 [收缩压 (BP) 截止值为 130 mmHg]。观察到的高血压事件发生率与弗雷明汉心脏预测的高血压事件发生率进行了比较。我们还评估了依鲁替尼治疗后的高血压与其他主要不良心血管事件 (MACE) 发生的关系，包括心律失常、心肌梗塞、中风、心力衰竭、和心血管死亡。此外，我们根据药物类别评估了抗高血压药物对依鲁替尼相关高血压的预防和调节作用。总体而言，78.3% 的依鲁替尼使用者在中位 30 个月内出现了新的或恶化的高血压 [平均收缩压增加 5.2 mmHg ({加减}20.7)]。71.6% 的依鲁替尼使用者发生了新的高血压（每 1,000 人年观察到 467 例 vs. Framingham 预测的病例为 39 例），达到 50% 的累积发病率时间为 4.2 个月。在没有既往高血压的患者中，17.7% 的人发展为高度（血压 >160/100mmHg）高血压。在包含已知 MACE 预测因子的多变量回归中，新发或恶化的高血压与增加的 MACE 相关 [风险比 (HR) 2.17, 95%CI 1.08-4.38]。没有单一抗高血压类别与预防或控制依鲁替尼相关的高血压相关。然而，开始降压治疗与较低的 MACE 风险相关（HR 0.40，CI 0.24-0.66）。总的来说，这些数据表明依鲁替尼与高血压的发病率和严重程度的显着增加有关，并且高血压的发展可能表明随后发生心脏毒性事件的风险更高。