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β肾上腺素能受体阻滞剂与肝癌患者肝癌死亡率的全国队列研究。

Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients.

机构信息

Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.

Department of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Scand J Gastroenterol. 2020 May;55(5):597-605. doi: 10.1080/00365521.2020.1762919. Epub 2020 May 15.

Abstract

β-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of β-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014. Patients were identified from the Swedish Cancer Register ( = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures. Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, β-blocker use at cancer diagnosis [ = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72-0.94); = .005]. Statistically significant associations were observed for non-selective [0.71 (0.55-0.91); = .006], β1-receptor selective [0.86 [0.75-1.00); = .049] and lipophilic [0.78 (0.67-0.90); = .001] β-blockers. No association was observed for hydrophilic β-blockers [1.01 (0.80-1.28); = .906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67-1.01); = .062]. β-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective β-blocker use.

摘要

β-肾上腺素能信号已被牵连到肝细胞癌 (HCC) 的发病机制中,但临床研究的证据有限。在这项基于全国人群的队列研究中,我们研究了瑞典在 2006 年至 2014 年间诊断为原发性 HCC 的患者中,β-肾上腺素能受体阻滞剂与癌症特异性死亡率之间的可能关联。患者从瑞典癌症登记处 ( = 2104) 中确定,并随访至 2015 年 12 月 31 日。我们使用 Cox 回归来评估癌症诊断前 90 天内开具的 β 阻滞剂与从死因登记处确定的肝癌死亡率之间的关联,同时控制社会人口统计学因素、肿瘤特征、合并症、其他药物和治疗程序。在中位随访 9.9 个月期间,有 1601 名患者死亡 (其中 1309 人死于肝癌)。与未使用相比,癌症诊断时使用β阻滞剂 [ = 714 (主要为流行使用,93%)] 与肝癌死亡率降低相关 [0.82 (0.72-0.94); =.005]。对于非选择性 [0.71 (0.55-0.91); =.006]、β1 受体选择性 [0.86 [0.75-1.00); =.049] 和脂溶性 [0.78 (0.67-0.90); =.001]β 阻滞剂,观察到有统计学意义的关联。对于亲水性β阻滞剂 [1.01 (0.80-1.28); =.906] 或其他降压药物,未观察到关联。进一步分析表明,观察到的较低肝癌死亡率仅限于诊断时局部疾病的患者 [0.82 (0.67-1.01); =.062]。在这项 HCC 患者的全国队列研究中,β 阻滞剂的使用与较低的肝癌死亡率相关。非选择性β阻滞剂的使用与更大幅度的负相关。

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