Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality
Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality
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DOI：
10.1001/jama.2020.11301
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发表时间：
2020-07-14
影响因子：
120.7
通讯作者：
Kober, Lars
中科院分区：
文献类型：
--
作者：
Fosbol, Emil L.;Butt, Jawad H.;Kober, Lars
重要性已经假设血管紧张素转换酶抑制剂(ACEI)/血管紧张素受体阻滞剂(ARB)可能使患者更容易患上2019年冠状病毒病(新冠肺炎)，并通过上调病毒的功能受体血管紧张素转换酶2而使患者更容易出现更差的预后。目的研究血管紧张素转换酶/ARBS的使用是否与新冠肺炎的诊断和COVID-19患者的更差预后相关。设计、设置和参与者检查新冠肺炎患者的预后。使用ICD-10编码对2020年2月22日至5月4日期间的新冠肺炎患者进行识别，并从确诊之日起至结果或研究结束(2020年5月4日)进行随访。为了研究新冠肺炎的易感性，采用病例对照嵌套的COX回归模型，对2020年2月1日至5月4日期间的一组高血压患者使用血管紧张素转换酶抑制剂/血管紧张素转换酶抑制剂和其他抗高血压药物与新冠肺炎诊断的发生率之间的关系进行了检验。结果表明，血管紧张素转换酶抑制剂/血管紧张素转换酶抑制剂的使用被定义为在指标日期前6个月服用处方药。在回顾队列研究中，主要结果和措施是死亡，次要结果是死亡或严重新冠肺炎的综合结果。结果在回顾性队列研究中，纳入4 480例新冠肺炎患者(中位年龄54.7岁[四分位数范围40.9~72.0岁；男性占47.9%)。ACEI/ARBS使用者895人(20.0%)，非使用者3585人(80.0%)。在ACEI/ARB组中，18.1%的患者在30天内死亡，而在非使用组中为7.3%，但在调整了年龄、性别和病史(调整后的危险比[HR]，0.83[95%CI，0.67-1.03])后，这种相关性并不显著。使用ACEI/ARB的患者在30天内死亡或重度新冠肺炎的发生率为31.9%，而不使用ACEI/ARB的患者为14.2%(调整后的HR，1.04[95%CI，0.89-1.23])。在新冠肺炎易感性的嵌套病例对照分析中，571例有新冠肺炎病史的患者(中位年龄为73.9岁；54.3%的男性)与5710例年龄和性别匹配的对照组中，既往有高血压病史但没有新冠肺炎病史的患者进行了比较。在新冠肺炎患者中，86.5%的患者使用血管紧张素转换酶抑制剂/ARBS，而对照组的85.4%；与其他抗高血压药物相比，使用血管紧张素转换酶抑制剂/ARB并不显著增加新冠肺炎的发生率(调整后的HR，1.05[95%CI，0.80~1.36])。结论在高血压患者中，既往使用血管紧张素转换酶抑制剂/ARBS与新冠肺炎的诊断无关，在诊断为新冠肺炎的患者中，与死亡率或严重疾病无关。这些发现不支持在新冠肺炎大流行的背景下临床表明的血管紧张素转换酶/血管紧张素转换酶抑制剂/血管紧张素转换酶B药物的停用。
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.