长期使用影响肾素-血管紧张素系统的药物与癌症风险：一项基于人群的病例对照研究。
Long term use of drugs affecting the renin-angiotensin system and the risk of cancer: a population-based case-control study.
机构信息
Research Unit of Clinical Pharmacology, University of Southern Denmark, Odense C, Denmark.
出版信息
Br J Clin Pharmacol. 2012 Jul;74(1):180-8. doi: 10.1111/j.1365-2125.2012.04170.x.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• A recent meta-analysis has suggested an increased risk of cancer among users of angiotensin receptor blockers.
WHAT THIS STUDY ADDS
• Within the limitations of an observational study there is no difference in the cancer incidence between users of drugs affecting the renin-angiotensin system and users of other antihypertensives. • No consistent dose or duration dependency could be demonstrated for angiotensin reeptor blockers and angiotensin converting enzyme inhibitors.
AIMS
A recent meta-analysis of clinical trials has demonstrated a small excess of cancers in persons who had been allocated to angiotensin receptor blockers (ARBs). We undertook this observational study to look at dose-response and dose-duration effects and look for specificity with respect to outcome. Use of angiotensin converting enzyme inhibitors (ACEIs) was included in the main analysis since ACEIs share pharmacological properties with ARBs.
METHODS
We identified 149 417 incident cancer cases in Denmark during the period 2000-2005. Four controls, matched by age and gender, were selected for each case by a risk-set sampling. Data on medication were retrieved from the Danish National Prescription Registry. We defined long term exposure as at least 1000 defined daily doses redeemed within the past 5 years. Confounders were controlled by conditional logistic regression.
RESULTS
The odds ratio (OR) associating long term drug use with incident cancer was 1.12 (95% CI 1.06, 1.18), 1.17 (95% CI 1.14, 1.20), 1.23 (95% CI 1.20, 1.26), 1.18 (95% CI 1.14, 1.22), 1.25 (95% CI 1.22, 1.28), 1.37 (95% CI 1.21, 1.54), 1.29 (95% CI 1.22, 1.37) for ARBs, ACEIs, calcium channel blockers, β-adrenoceptor blockers, thiazide diuretics and α-adrenoceptor blockers. No consistent dose-duration or dose-response association could be demonstrated for ARBs or ACEIs.
CONCLUSIONS
The indication or possibly threshold for prescribing antihypertensives appears to be related to a small increase in cancer risk. The ARB-cancer association is probably too weak to be addressed in observational studies, given their limitations.
已知本课题相关信息
• 最近的一项荟萃分析表明，血管紧张素受体阻滞剂使用者的癌症风险增加。
本研究新发现
• 在观察性研究的限制内，使用影响肾素-血管紧张素系统的药物和其他降压药的患者的癌症发病率没有差异。• 未发现血管紧张素受体阻滞剂和血管紧张素转换酶抑制剂的剂量或持续时间依赖性。
目的
最近对临床试验的荟萃分析表明，接受血管紧张素受体阻滞剂（ARB）治疗的患者癌症发病率略有增加。我们进行了这项观察性研究，以研究剂量-反应和剂量-持续时间的影响，并寻找与结果相关的特异性。在主要分析中还包括血管紧张素转换酶抑制剂（ACEI），因为 ACEI 与 ARB 具有药理学特性。
方法
我们在 2000-2005 年期间确定了丹麦 149417 例新发癌症病例。通过风险集抽样，为每个病例匹配了 4 名年龄和性别相匹配的对照。从丹麦国家处方登记处检索药物数据。我们将长期暴露定义为过去 5 年内至少使用 1000 个定义日剂量。通过条件逻辑回归控制混杂因素。
结果
与长期药物使用相关的新发癌症的比值比（OR）为 1.12（95%CI 1.06，1.18），1.17（95%CI 1.14，1.20），1.23（95%CI 1.20，1.26），1.18（95%CI 1.14，1.22），1.25（95%CI 1.22，1.28），1.37（95%CI 1.21，1.54），1.29（95%CI 1.22，1.37）分别为 ARB、ACEI、钙通道阻滞剂、β-肾上腺素受体阻滞剂、噻嗪类利尿剂和α-肾上腺素受体阻滞剂。ARB 或 ACEI 未显示出一致的剂量-持续时间或剂量-反应关联。
结论
降压药物的适应证或可能的阈值似乎与癌症风险略有增加有关。考虑到观察性研究的局限性，ARB 与癌症的关联可能太弱，无法在观察性研究中解决。
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