Batra Akshee, Patel Brijesh, Addison Daniel, Baldassarre Lauren A, Desai Nihar, Weintraub Neal, Deswal Anita, Hussain Zeeshan, Brown Sherry-Ann, Ganatra Sarju, Agarwala Vivek, Parikh Purvish M, Fradley Michael, Ghosh Arjun, Guha Avirup
Department of Medicine, University of Vermont Medical Center, Burlington, Vermont, USA.
Department of Cardiology, West Virginia University, Morgantown, West Virginia, USA.
Open Heart. 2021 Dec;8(2). doi: 10.1136/openhrt-2021-001849.
Antimicrotubular agents are among the most commonly used classes of chemotherapeutic agents, but the risk of cardiovascular adverse events (CVAEs) remains unclear. Our objective was to study the CVAEs associated with antimicrotubular agents.
The Food and Drug Administration's Adverse Event Reporting System was used to study CVAEs in adults from 1990 to 2020. Reported single-agent (only taxane or vinca alkaloid) CVAEs were compared with combination therapy (with at least one of the four major cardiotoxic drugs: anthracycline, HER2Neu inhibitors, tyrosine kinase inhibitors and checkpoint inhibitors) using adjusted polytomous logistic regression.
Over 30 years, 134 398 adverse events were reported, of which 18 426 (13.4%) were CVAEs, with 74.1% due to taxanes and 25.9% due to vinca alkaloids. In 30 years, there has been a reduction in the proportion of reported CVAEs for taxanes from 15% to 11.8% (Cochran-Armitage P-trends <0.001) with no significant change in the proportion of reported CVAEs for vinca alkaloids (9.2%-11.7%; P-trends=0.06). The proportion of reported CVAEs was lower in both taxane and vinca alkaloid monotherapy versus combination therapy (reporting OR=0.50 and 0.55, respectively). Anthracyclines and HER2Neu inhibitor combinations with taxanes or vinca alkaloids primarily drove the higher burden of combination CVAEs. Hypertension requiring hospitalisation and heart failure was significantly lower in monotherapy versus combination antimicrotubular agent therapy.
Antimicrotubular agents are associated with CVAEs, especially in combination chemotherapy regimens. Based on this study, we suggest routine cardiovascular assessment of patients with cancer before initiating antimicrotubular agents in combination therapy.
抗微管药物是最常用的化疗药物类别之一，但心血管不良事件（CVAEs）的风险仍不明确。我们的目的是研究与抗微管药物相关的CVAEs。
利用美国食品药品监督管理局的不良事件报告系统研究1990年至2020年成人中的CVAEs。使用调整后的多分类逻辑回归，将报告的单药（仅紫杉烷或长春花生物碱）CVAEs与联合治疗（使用四种主要心脏毒性药物中的至少一种：蒽环类药物、HER2Neu抑制剂、酪氨酸激酶抑制剂和检查点抑制剂）进行比较。
在30年期间，共报告了134398例不良事件，其中18426例（13.4%）为CVAEs，74.1%归因于紫杉烷，25.9%归因于长春花生物碱。30年来，紫杉烷报告的CVAEs比例从15%降至11.8%（ Cochr an-Armitage趋势检验P<0.001），而长春花生物碱报告的CVAEs比例无显著变化（9.2%-11.7%；趋势检验P=0.06）。紫杉烷和长春花生物碱单药治疗中报告的CVAEs比例均低于联合治疗（报告的比值比分别为0.50和0.55）。蒽环类药物和HER2Neu抑制剂与紫杉烷或长春花生物碱的联合使用主要导致联合CVAEs负担加重。与抗微管药物联合治疗相比，单药治疗中需要住院治疗的高血压和心力衰竭显著更低。
抗微管药物与CVAEs相关，尤其是在联合化疗方案中。基于本研究，我们建议在开始抗微管药物联合治疗前，对癌症患者进行常规心血管评估。
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