Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study
Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study
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DOI：
10.1016/s0140-6736(20)31030-8
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发表时间：
2020-05-30
期刊：
影响因子：
168.9
通讯作者：
Rodriguez-Puyol, Diego
中科院分区：
文献类型：
--
作者：
de Abajo, Francisco J.;Rodriguez-Martin, Sara;Rodriguez-Puyol, Diego
背景人们对肾素-血管紧张素-醛固酮系统（RAAS）抑制剂可能使个体易患严重COVID-19的可能性表示担忧;然而，缺乏流行病学证据。我们报告了自COVID-19爆发以来在西班牙马德里进行的一项病例-人群研究的结果。方法在这项病例-人群研究中，我们连续选择了2020年3月1日至3月24日期间在马德里的7家医院住院的18岁或18岁以上的PCR确诊的COVID-19患者。作为参考组，我们从西班牙初级卫生保健数据库Base de datos帕拉la Investigacion Farmacoepidemiologica en Atencion Primaria（BIFAP）中随机抽取每个病例10名患者，年龄、性别、地区（即马德里）和入院日期（月和日;索引日期）分别匹配。我们从病例和对照组的电子临床记录中提取了索引日期（即当前使用）前一个月的合并症和处方信息。关注的结局是COVID-19患者入院。为了尽量减少适应症的混杂因素，主要分析重点评估了需要住院的COVID-19与使用RAAS抑制剂之间的相关性，与使用其他降压药物相比。我们使用条件logistic回归计算了比值比（OR）和95%CI，并对年龄、性别、心血管合并症和危险因素进行了调整。该研究方案已在欧盟授权后研究电子注册表（EUPAS 34437）中注册。结果我们收集了1139例病例和11390例人群对照的数据。在这些病例中，444例（39.0%）为女性，平均年龄为69.1岁（SD 15.4），尽管性别和年龄匹配，但与对照组相比，既存心血管疾病（OR 1.98，95%CI 1.62-2.41）和危险因素（1.46，1.23-1.73）的病例比例显著较高。与其他降压药使用者相比，RAAS抑制剂使用者因COVID-19需要住院的调整OR为0.94（95%CI 0.77-1.15）。使用血管紧张素转换酶抑制剂（校正OR 0.80，0.64-1.00）或血管紧张素受体阻滞剂（1.10，0.88-1.37）均未观察到风险增加。性别、年龄和背景心血管风险并没有改变使用RAAS抑制剂与需要住院的COVID-19之间的校正OR，而在使用RAAS抑制剂的糖尿病患者中发现需要住院的COVID-19风险降低（校正OR 0.53，95%CI 0.34-0.80）。调整后的OR在COVID-19的严重程度之间相似。解释RAAS抑制剂不会增加COVID-19需要住院的风险，包括致命病例和入住重症监护室的病例，不应为预防严重的COVID-19病例而停用。
Background Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19.Methods In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigacion Farmacoepidemiologica en Atencion Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437.Findings We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39.0%) were female and the mean age was 69.1 years (SD 15.4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1.98, 95% CI 1.62-2.41) and risk factors (1.46, 1.23-1.73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0.94 (95% CI 0.77-1.15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0.80, 0.64-1.00) or angiotensin-receptor blockers (1.10, 0.88-1.37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0.53, 95% CI 0.34-0.80). The adjusted ORs were similar across severity degrees of COVID-19.Interpretation RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19.