Importance It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2. Objective To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. Design, Setting, and Participants To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020. Exposures ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. Main Outcomes and Measures In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. Results In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). Conclusions and Relevance Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.

中文翻译：

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血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂使用与 COVID-19 诊断和死亡率的关联

重要性 据推测，血管紧张素转换酶抑制剂 (ACEI)/血管紧张素受体阻滞剂 (ARB) 可能使患者更容易感染 2019 年冠状病毒病 (COVID-19)，并通过上调病毒的功能性受体血管紧张素使患者预后更差- 转化酶 2. 目的 研究 ACEI/ARBs 的使用是否与 COVID-19 诊断和 COVID-19 患者的不良预后相关。设计、设置和参与者为了检查 COVID-19 患者的结果，使用来自丹麦国家行政登记处的数据进行了一项回顾性队列研究。使用 ICD-10 代码识别 2020 年 2 月 22 日至 5 月 4 日期间的 COVID-19 患者，并从诊断之日到结果或研究期结束（2020 年 5 月 4 日）进行随访。检查对 COVID-19 的易感性，具有嵌套病例对照框架的 Cox 回归模型用于检查 2 月 1 日至 5 月 4 日一组高血压患者中 ACEI/ARB 与其他抗高血压药物的使用与 COVID-19 诊断发生率之间的关联, 2020. 暴露 ACEI/ARB 使用被定义为索引日期前 6 个月的处方填充。主要结果和措施 在回顾性队列研究中，主要结果是死亡，次要结果是死亡或严重 COVID-19 的复合结果。在嵌套病例对照易感性分析中，结果是 COVID-19 诊断。结果 在回顾性队列研究中，共纳入了 4480 名 COVID-19 患者（中位年龄，54.7 岁 [四分位距，40.9-72.0]；47.9% 为男性）。有 895 名 ACEI/ARB 用户 (20.0%) 和 3585 名非用户 (80.0%)。在 ACEI/ARB 组中，18.1% 的患者在 30 天内死亡，而未使用组为 7.3%，但在调整年龄、性别和病史后，这种关联并不显着（调整后的风险比 [HR]，0.83 [95% CI , 0.67-1.03])。到 30 天时，31.9% 的 ACEI/ARB 用户和 14.2% 的非用户发生死亡或严重 COVID-19（调整后的 HR，1.04 [95% CI，0.89-1.23]）。在对 COVID-19 易感性的嵌套病例对照分析中，将 571 名 COVID-19 和既往高血压患者（中位年龄，73.9 岁；54.3% 男性）与 5710 名年龄和性别匹配的既往高血压但未感染 COVID 的对照组进行了比较-19。在 COVID-19 患者中，86.5% 使用 ACEI/ARB，而对照组为 85.4%；与其他抗高血压药物相比，使用 ACEI/ARB 与较高的 COVID-19 发病率没有显着相关性（调整后的 HR，1.05 [95% CI，0.80-1.36]）。结论和相关性 先前使用 ACEI/ARB 与高血压患者的 COVID-19 诊断或被诊断为 COVID-19 的患者的死亡率或严重疾病无显着相关性。这些发现不支持在 COVID-19 大流行的背景下停用 ACEI/ARB 药物。