ARB类可能增加肿瘤的风险

大**烟

Lancet Oncol. 2010 Jun 11. [Epub ahead of print]

Angiotensin-receptor blockade and risk of cancer: meta-**ysis of randomised controlled trials.

Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC.

Harrington-McLaughlin Heart & Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Abstract

BACKGROUND:
Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-**ysis of randomised controlled trials of these drugs.

METHODS:
We searched Medline, Scopus (including Embase), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the US Food and Drug Administration website for studies published before November, 2009, that included any of the seven currently available ARBs. Randomised controlled trials with an ARB given in at least one group, with a follow-up of at least 1 year, and that enrolled at least 100 patients were included. New-cancer data were available for 61 590 patients from five trials. Data on common types of solid organ cancers were available for 68 402 patients from five trials, and data on cancer deaths were available for 93 515 patients from eight trials.

FINDINGS:
Telmisartan was the study drug in 30 014 (85.7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016). When **ysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04-1.18, p=0.001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0.9%vs 0.7%, RR 1.25, 1.05-1.49; p=0.01). No statistically significant difference in cancer deaths was observed (1.8%vs 1.6%, RR 1.07, 0.97-1.18; p=0.183). INTERPRETATION: This meta-**ysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation.

FUNDING: None.

大**烟

血管紧张素受体阻滞剂和癌症风险：随机、对照试验的Meta分析

摘要

背景
ARB类是被广泛用来治疗高血压、心衰、糖尿病肾病、而且近来用于减少心血管风险的一类药物。 实验研究显示RAS系统，尤其是AngII 1型和2型受体，可以调控细胞增殖、血管新生和肿瘤的进展。我们做了一项关于这类药物的随机、对照试验的Meta分析，来评价ARB类是否影响肿瘤的发生。

方法
我们检索了Medline、Scopus（包括Embase）、Cochrane对照试验注册中心、Cochrane系统回顾数据库和美国FDA网站，在2009年11月以前公开发表的研究，包括现有的7项使用ARB类药物的研究。 这些被纳入的随机、对照研究，至少有一组给予ARB、随访1年、包括100名患者。新发生肿瘤的数据来自于5项试验的61590名患者 。常见类型的实体瘤的数据来自于5项试验的68402名患者，肿瘤死亡的数据来自于8项试验的93515名患者。

发现
使用ARB类药物中，有30014名患者（占85.7%）使用替米沙坦作为研究用药，他们作为新发生肿瘤数据的一部分。随机安排使用ARB类药物的患者与对照组比较，有明显的新发生肿瘤的风险。（分别是7.2%对6.0%，RR=1.08,95%置信区间[1.01，1.15]，P=0.016） 。当分析限定为肿瘤是预先指定的终点事件时，RR=1.11（95%置信区间=1.04-1.18， p=0·001）。在特定实体器官肿瘤检测中，在随机给予ARB类药物的患者与对照组比较，只有新发生的肺癌明显高于对照组（0.9%比0.7%，RR=1.25,95%置信区间=1·05—1·49; p=0·01）。肿瘤的死亡没有明显差异。（1.8%比1.6%，RR=1.07,95%置信区间=0.97-1.18， p=0·183）。

解释
这个随机、对照试验的Meta分析表明，ARB类与新发生癌症的诊断的轻度增高有关。 鉴于限定的数据，这个研究不可能得出肿瘤的确切风险与特定药物有关的结论。这个发现告诫我们要进一步的研究。

资金
无。