抗高血压治疗与癌症风险：一项个体参与者数据荟萃分析。

Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis.

机构信息

Deep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK; National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Deep Medicine, Oxford Martin School, University of Oxford, Oxford, UK; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

出版信息

Lancet Oncol. 2021 Apr;22(4):558-570. doi: 10.1016/S1470-2045(21)00033-4.

DOI:10.1016/S1470-2045(21)00033-4

PMID:33794209

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8024901/

Abstract

BACKGROUND

Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials.

METHODS

We searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), β blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283).

FINDINGS

33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4·2 years (IQR 3·0-5·0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0·99 [95% CI 0·95-1·04] for ACEIs; 0·96 [0·92-1·01] for ARBs; 0·98 [0·89-1·07] for β blockers; 1·01 [0·95-1·07] for thiazides), with the exception of calcium channel blockers (1·06 [1·01-1·11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1·00 [95% CI 0·93-1·09] for ACEIs; 0·99 [0·92-1·06] for ARBs; 0·99 [0·89-1·11] for β blockers; 1·04 [0·96-1·13] for calcium channel blockers; 1·00 [0·90-1·10] for thiazides).

INTERPRETATION

We found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.

FUNDING

British Heart Foundation, National Institute for Health Research, Oxford Martin School.

摘要

背景

一些研究表明降压药物与癌症之间存在关联，但目前证据尚无定论。因此，我们旨在通过对随机临床试验的个体患者数据进行大规模荟萃分析来研究这种关联。

方法

我们从 1966 年 1 月 1 日至 2019 年 9 月 1 日在 PubMed、MEDLINE、The Cochrane Central Register of Controlled Trials 和 ClinicalTrials.gov 中搜索了可能符合条件的随机对照试验。符合条件的研究是将一种降压药物与安慰剂、无效对照或其他降压药物进行比较的随机对照试验。我们还要求每个治疗组的随访时间至少为 1000 人年。没有癌症事件信息的试验被排除在外。我们向符合条件的试验的作者请求了个体参与者数据。我们从符合条件的试验中汇总了个体参与者的数据，并在一个阶段的个体参与者数据和网络荟萃分析中评估了血管紧张素转换酶抑制剂（ACEIs）、血管紧张素 II 受体阻滞剂（ARBs）、β受体阻滞剂、钙通道阻滞剂和噻嗪类利尿剂对癌症风险的影响。按试验分层的特定原因固定效应 Cox 回归模型用于计算风险比（HRs）。主要结局是任何癌症事件，定义为随机分组后首次诊断出的任何癌症。本研究在 PROSPERO（CRD42018099283）中注册。

结果

33 项试验符合纳入标准，包括 260447 名参与者，其中有 15012 例癌症事件。纳入参与者的中位随访时间为 4.2 年（IQR 3.0-5.0）。在个体参与者数据荟萃分析中，将每种药物类别与所有其他对照药物进行比较时，没有发现任何降压药物类别与癌症风险之间存在关联（ACEIs 的 HR 0.99 [95%CI 0.95-1.04]；ARBs 的 HR 0.96 [0.92-1.01]；β受体阻滞剂的 HR 0.98 [0.89-1.07]；噻嗪类的 HR 1.01 [0.95-1.07]），但钙通道阻滞剂除外（HR 1.06 [1.01-1.11]）。在与安慰剂比较药物类别的网络荟萃分析中，我们发现没有任何药物类别会增加癌症风险（ACEIs 的 HR 1.00 [95%CI 0.93-1.09]；ARBs 的 HR 0.99 [0.92-1.06]；β受体阻滞剂的 HR 0.99 [0.89-1.11]；钙通道阻滞剂的 HR 1.04 [0.96-1.13]；噻嗪类的 HR 1.00 [0.90-1.10]）。