Department of Haematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan.
Department of Haematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan
Open Heart. 2022 Dec;9(2). doi: 10.1136/openhrt-2022-002135.
Cancer treatment with vascular endothelial growth factor signalling pathway (VSP) inhibitors frequently causes hypertension. Although previous reports suggested that the antihypertensive drug renin-angiotensin system inhibitor (RASI) may have a positive synergistic effect with VSP inhibitors, the actual impact on clinical outcomes is unknown.
The study aims to clarify whether RASIs exhibit clinical benefits for patients with cancer with hypertension.
From the Longevity Improvement and Fair Evidence Study database, comprising Japanese claims data between 2016 and 2020, we reviewed 2380 patients treated with VSP inhibitors who received antihypertensive treatment during cancer therapy. The patients were classified into two groups: with-RASI (n=883) and without-RASI (n=1497). In addition, 1803 of these patients treated for hypertension with RASI-only (n=707) or calcium channel blocker-only (n=1096) were also reviewed. The time-to-treatment failure (TTF), the interval from initiation of chemotherapy to its discontinuation, was applied as the primary endpoint.
The median TTFs were 167 (60-382) days in the with-RASI group and 161 (63-377) days in the without-RASI group (p=0.587). All models, including Cox proportional hazard models and multiple propensity score models, did not reveal the superiority of with-RASI treatment. In the propensity score matching model, the HR for treatment with-RASI compared with that for without-RASI was 0.96 (95% CI 0.86 to 1.06, p=0.386). In addition, the TTFs of RASI-only were not superior to calcium channel blocker-only (p=0.584).
RASIs for hypertension do not benefit clinical outcomes during cancer therapy with VSP inhibitors. In addition, RASIs and calcium channel blockers have comparable clinical efficacy as first-line antihypertensive.
血管内皮生长因子信号通路（VSP）抑制剂治疗癌症常导致高血压。虽然之前的报告表明血管紧张素转化酶抑制剂（RASI）可能与 VSP 抑制剂具有积极的协同作用，但对临床结果的实际影响尚不清楚。
本研究旨在阐明 RASI 是否对高血压癌症患者具有临床获益。
从 2016 年至 2020 年期间的日本理赔数据组成的长寿改善和公平证据研究数据库中，我们回顾了 2380 名接受 VSP 抑制剂治疗并在癌症治疗期间接受降压治疗的患者。患者被分为两组：使用 RASI（n=883）和不使用 RASI（n=1497）。此外，还回顾了其中 1803 名使用 RASI 单药（n=707）或钙通道阻滞剂单药（n=1096）治疗高血压的患者。治疗失败时间（TTF），即从开始化疗到停止化疗的时间，被用作主要终点。
使用 RASI 组的中位 TTF 为 167（60-382）天，不使用 RASI 组为 161（63-377）天（p=0.587）。所有模型，包括 Cox 比例风险模型和多倾向评分模型，均未显示使用 RASI 治疗的优越性。在倾向评分匹配模型中，与不使用 RASI 相比，使用 RASI 的 HR 为 0.96（95%CI 0.86-1.06，p=0.386）。此外，RASI 单药的 TTF 并不优于钙通道阻滞剂单药（p=0.584）。
高血压的 RASI 并不能改善 VSP 抑制剂癌症治疗期间的临床结局。此外，RASI 和钙通道阻滞剂作为一线降压药具有相当的临床疗效。
