Intensified monitoring of circadian blood pressure and heart rate before and after intravitreous injection of bevacizumab: preliminary findings of a pilot study

Background A dose-dependent increase in arterial blood pressure (BP) was seen during bevacizumab treatment given intravenously for metastatic carcinoma. Because low systemic levels can also be expected after the intravitreal administration of bevacizumab, we looked for possible haemodynamic reactions of patients at higher risk of developing cardiovascular events after bevacizumab injection. Methods Ambulatory BP was monitored in 14 hypertensive patients receiving 1.25 mg intraocular bevacizumab for either choroidal neovascularization (CNV) or retinal proliferation associated with central retinal vein occlusion (CRVO). Circadian measurement was carried out twice, first at least 24 h prior to injection and second 72 h afterwards. Baseline evaluation before injection was compared with values taken in a matched control group. Taking a small random sample of two patients, serum concentration of bevacizumab and VEGF-A was measured at several time points. Results High incidence of pathologic BP values was found in the pre-injection measurement, even under anti-hypertensive treatment of the patients with CNV or CRVO. No general increase in BP was seen after the intravitreal injection (P = 0.01), although significantly reduced nocturnal dipping occurred as compared to before the injection (P = 0.006). Individual patients showed a rise in BP load subsequent to injection. A decline in serum VEGF-A was found to correspond to measureable levels of serum bevacizumab (up to 90 ng/ml). Conclusions Before the intravitreal injection, BP values were increased in the majority of the patients. The elevated BP load might be related to probable pre-injection stressors. There seems to be no general rise in mean BP, heart rate and pulse pressure after intravitreal bevacizumab, although a decrease in serum VEGF-A can occur in individual patients. The reduced nocturnal dipping could be caused by pharmacodynamic effects on the vasal tone; this preliminary but striking finding warrants further investigation.

背景 在静脉给予贝伐单抗治疗转移性癌期间，观察到动脉血压（BP）呈剂量依赖性升高。由于玻璃体内注射贝伐单抗后也可能出现较低的全身水平，我们对贝伐单抗注射后发生心血管事件风险较高的患者寻找可能的血液动力学反应。 方法 对14例因脉络膜新生血管（CNV）或视网膜中央静脉阻塞（CRVO）相关的视网膜增殖而接受1.25mg眼内贝伐单抗治疗的高血压患者进行动态血压监测。昼夜测量进行两次，第一次在注射前至少24小时，第二次在注射后72小时。将注射前的基线评估与匹配对照组的值进行比较。抽取两名患者的小随机样本，在几个时间点测量贝伐单抗和血管内皮生长因子 - A（VEGF - A）的血清浓度。 结果 在注射前测量中发现病理血压值的发生率较高，即使CNV或CRVO患者正在接受抗高血压治疗。玻璃体内注射后未观察到血压普遍升高（P = 0.01），尽管与注射前相比，夜间血压下降幅度显著减小（P = 0.006）。个别患者在注射后血压负荷升高。发现血清VEGF - A的下降与可测量的血清贝伐单抗水平（高达90ng/ml）相对应。 结论 在玻璃体内注射前，大多数患者的血压值升高。血压负荷升高可能与注射前可能的应激源有关。玻璃体内注射贝伐单抗后，平均血压、心率和脉压似乎没有普遍升高，尽管个别患者血清VEGF - A可能下降。夜间血压下降幅度减小可能是由于对血管张力的药效学作用所致；这一初步但显著的发现值得进一步研究。