丹麦哥本哈根大学医院Emil L. Fosbøl团队分析了血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂的使用与COVID-19确诊和死亡的相关性。该研究于2020年6月19日发表于《美国医学会杂志》上。
为了确定ACEI / ARBs的使用是否与COVID-19的诊断和COVID-19患者的预后较差有关，研究组使用丹麦国家行政管理部门的数据，进行了一项回顾性队列研究，筛选出2020年2月22日至5月4日患有COVID-19的患者，采用Cox回归模型分析ACEI / ARB与其他降压药的使用和队列中COVID-19确诊率之间的关联。
研究组共纳入了4480例COVID-19患者，中位年龄为54.7岁，男性占47.9％，895例患者（20.0％）服用ACEI / ARB，3585例（80.0％）未服用。 ACEI / ARB组在30天内的死亡率为18.1％，而未服用组为7.3％，但在对年龄、性别和病史等因素进行校正后，这种关联并不显著，风险比为0.83。第30天时，ACEI / ARB组中有31.9％的患者发生死亡或重症COVID-19，而未服用组中有14.2％，校正后的风险比为1.04。
在对COVID-19易感性的巢式病例对照分析中，研究组将571例既往有高血压的COVID-19患者（中位年龄为73.9岁，男性占54.3％）与5710例年龄和性别相匹配的既往有高血压但非COVID-19的对照队列进行了比较。在COVID-19的人群中，86.5％的患者服用ACEI / ARB，而对照组为85.4％；与其他降压药相比，ACEI / ARB的使用与COVID-19的较高发生率没有显著相关性。
研究组得出结论，在高血压患者中，此前服用过ACEI / ARBs与COVID-19确诊不相关；在确诊COVID-19的患者中，ACEI / ARB的使用与死亡或重症亦无显著相关性。
Title: Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality
Author: Emil L. Fosbl, Jawad H. Butt, Lauge stergaard, Charlotte Andersson, Christian Selmer, Kristian Kragholm, Morten Schou, Matthew Phelps, Gunnar H. Gislason, Thomas A. Gerds, Christian Torp-Pedersen, Lars Kber
Abstract: 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.