Abiodun Aderonke T, Ju Chengsheng, Welch Catherine A, Lai Jennifer, Tyrer Freya, Chambers Pinkie, Paley Lizz, Vernon Sally, Deanfield John, de Belder Mark, Rutherford Mark J, Lambert Paul C, Slater Sarah, Shiu Kai-Keen, Wei Li, Peake Michael D, Adlam David, Manisty Charlotte
Institute of Cardiovascular Science, University College London, United Kingdom; Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom; National Disease Registration Service, NHS England, Wellington Place, Leeds, United Kingdom.
Institute of Cardiovascular Science, University College London, United Kingdom; National Disease Registration Service, NHS England, Wellington Place, Leeds, United Kingdom; Research Department of Practice and Policy, School of Pharmacy, University College London, United Kingdom.
JACC CardioOncol. 2025 Jun;7(4):345-356. doi: 10.1016/j.jaccao.2025.01.019. Epub 2025 Apr 8.
Fluoropyrimidine chemotherapy is administered first-line for many gastrointestinal cancers. However, patients with cardiovascular disease commonly receive alternative treatment due to cardiotoxicity concerns.
This study sought to assess the risks of all-cause mortality and acute cardiovascular events with fluoropyrimidine treatment.
We conducted an observational cohort study applying a target trial emulation framework to linked national cancer, cardiac, and hospitalization registry data from the Virtual Cardio-Oncology Research Initiative. Adults diagnosed with tumors eligible for fluoropyrimidine-based chemotherapy as first-line therapy were included. All-cause mortality and a composite of hospitalization for acute cardiovascular events (acute coronary syndrome, heart failure, cardiac arrhythmia, cardiac intervention, cardiac arrest, and cardiac death) were compared in patients treated with fluoropyrimidine-based chemotherapy vs alternative management. Adjusted, weighted pooled logistic regression models were used to estimate the 1-year risk difference (RD).
Among 103,110 patients (mean age 69.7 years, 59% male), the absolute risk of death at 1 year was significantly lower in fluoropyrimidine-treated patients (RD: -7.7%; 95% CI: -8.7% to -6.7%) with a small increased risk of acute cardiovascular events (RD: 0.9%; 95% CI: 0.0% to 1.9%). This was primarily due to arrhythmias (RD: 0.8%; 95% CI: 0.1% to 1.6%) and cardiac arrest (RD: 0.3%; 95% CI: 0.1% to 0.5%), with no increased risk of acute coronary syndromes including in the subgroup of patients with pre-existing coronary artery disease.
The markedly improved overall survival with fluoropyrimidines in patients with gastrointestinal cancer significantly outweighs the small risk of cardiac arrhythmia and arrest. Oncologists should take this into consideration for decision making to avoid undue clinical conservatism, particularly in patients with cardiovascular disease.
氟嘧啶化疗是多种胃肠道癌症的一线治疗方法。然而，由于担心心脏毒性，心血管疾病患者通常接受其他治疗。
本研究旨在评估氟嘧啶治疗导致的全因死亡率和急性心血管事件风险。
我们进行了一项观察性队列研究，应用目标试验模拟框架，对来自虚拟心脏肿瘤研究倡议的国家癌症、心脏和住院登记数据进行关联分析。纳入被诊断患有适合氟嘧啶类化疗作为一线治疗的肿瘤的成年人。比较接受氟嘧啶类化疗与接受其他治疗的患者的全因死亡率和急性心血管事件（急性冠状动脉综合征、心力衰竭、心律失常、心脏介入、心脏骤停和心源性死亡）的综合情况。使用调整后的加权合并逻辑回归模型估计1年风险差异（RD）。
在103110例患者（平均年龄69.7岁，59%为男性）中，氟嘧啶治疗组患者1年时的绝对死亡风险显著较低（RD：-7.7%；95%CI：-8.7%至-6.7%），急性心血管事件风险略有增加（RD：0.9%；95%CI：0.0%至1.9%）。这主要是由于心律失常（RD：0.8%；95%CI：0.1%至1.6%）和心脏骤停（RD：0.3%；95%CI：0.1%至0.5%），包括在已有冠状动脉疾病的患者亚组中，急性冠状动脉综合征风险没有增加。
胃肠道癌症患者使用氟嘧啶类药物显著改善的总体生存率明显超过心律失常和心脏骤停的小风险。肿瘤学家在决策时应考虑到这一点，以避免过度的临床保守主义，特别是在心血管疾病患者中。
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