Waliany Sarah, Sainani Kristin L, Park Lesley S, Zhang Chiyuan Amy, Srinivas Sandy, Witteles Ronald M
Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA.
JACC CardioOncol. 2019 Sep 24;1(1):24-36. doi: 10.1016/j.jaccao.2019.08.012. eCollection 2019 Sep.
This study quantified the change in blood pressure (BP) during antivascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy, compared BPs between TKIs, and analyzed change in BP during antihypertensive therapy.
TKIs targeting VEGF are associated with hypertension. The absolute change in BP during anti-VEGF TKI treatment is not well characterized outside clinical trials.
A retrospective single-center study included patients with metastatic renal cell carcinoma who received anti-VEGF TKIs between 2007 and 2018. Mixed models analyzed 3,088 BPs measured at oncology clinics.
In 228 patients (baseline systolic blood pressure [SBP] 130.2 ± 16.3 mm Hg, diastolic blood pressure [DBP] 76.8 ± 9.3 mm Hg), anti-VEGF TKIs were associated with mean increases in SBP of 8.5 mm Hg (p < 0.0001) and DBP of 6.7 mm Hg (p <0.0001). Of the anti-VEGF TKIs evaluated, axitinib was associated with the greatest BP increase, with an increase in SBP of 12.6 mm Hg (p < 0.0001) and in DBP of 10.3 mm Hg (p < 0.0001) relative to baseline. In pairwise comparisons between agents, axitinib was associated with greater SBPs than cabozantinib by 8.4 mm Hg (p = 0.004) and pazopanib by 5.1 mm Hg (p = 0.01). Subsequent anti-VEGF TKI courses were associated with small increases in DBP, but not SBP, relative to the first course. During anti-VEGF TKI therapy, calcium-channel blockers and potassium-sparing diuretic agents were associated with the largest BP reductions, with decreases in SBP of 5.6 mm Hg (p < 0.0001) and 9.9 mm Hg (p = 0.007), respectively.
Anti-VEGF TKIs are associated with increased BP; greatest increases are observed with axitinib. Calcium-channel blockers and potassium-sparing diuretic agents were associated with the largest reductions in BP.
本研究量化了抗血管内皮生长因子（VEGF）酪氨酸激酶抑制剂（TKI）治疗期间血压（BP）的变化，比较了不同TKI之间的血压，并分析了抗高血压治疗期间血压的变化。
靶向VEGF的TKI与高血压有关。在临床试验之外，抗VEGF TKI治疗期间血压的绝对变化尚未得到充分描述。
一项回顾性单中心研究纳入了2007年至2018年间接受抗VEGF TKI治疗的转移性肾细胞癌患者。混合模型分析了在肿瘤诊所测量的3088次血压。
在228例患者中（基线收缩压[SBP]130.2±16.3mmHg，舒张压[DBP]76.8±9.3mmHg），抗VEGF TKI与SBP平均升高8.5mmHg（p<0.0001）和DBP平均升高6.7mmHg（p<0.0001）相关。在评估的抗VEGF TKI中，阿昔替尼与最大的血压升高相关，相对于基线，SBP升高12.6mmHg（p<0.0001），DBP升高10.3mmHg（p<0.0001）。在各药物的两两比较中，阿昔替尼的SBP比卡博替尼高8.4mmHg（p=0.004），比帕唑帕尼高5.1mmHg（p=0.01）。相对于第一个疗程，后续的抗VEGF TKI疗程与DBP的小幅升高有关，但与SBP无关。在抗VEGF TKI治疗期间，钙通道阻滞剂和保钾利尿剂与最大的血压降低有关，SBP分别降低5.6mmHg（p<0.0001）和9.9mmHg（p=0.007）。
抗VEGF TKI与血压升高有关；阿昔替尼观察到的升高最大。钙通道阻滞剂和保钾利尿剂与最大的血压降低有关。
