Department of Population Health Sciences, Division of Health System Innovation and Research, University of Utah School of Medicine, Salt Lake City, UT, United States of America.
Department of Medicine, Renal-Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America.
PLoS One. 2021 Apr 23;16(4):e0248080. doi: 10.1371/journal.pone.0248080. eCollection 2021.
Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses.
In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days).
This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.
血管紧张素 II 受体阻滞剂（ARB）和血管紧张素转换酶抑制剂（ACEI）可能对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染的结局产生积极或消极的影响。我们使用活性对照设计、适当的协变量调整和阴性对照分析，研究了美国退伍军人高血压治疗中 ARB 或 ACEI 使用与冠状病毒病 2019（COVID-19）相关结局之间的关联。
在退伍军人事务部（Veterans Health Administration，VHA）接受高血压治疗的退伍军人中（2020 年 1 月 19 日至 2020 年 8 月 28 日），我们比较了（A）ARB/ACEI 使用者与非 ARB/ACEI 使用者（不包括有明确减少指示性偏倚的退伍军人）和（B）ARB 使用者与 ACEI 使用者在（1）SARS-CoV-2+门诊患者和（2）COVID-19 住院患者中的使用情况。主要结局是所有原因住院或死亡（门诊患者）和所有原因死亡（住院患者）。我们使用倾向评分加权 Cox 回归估计了危险比（HR）。加权后，暴露组之间的基线特征得到了很好的平衡。在门诊患者中，ARB/ACEI 使用者（n=2482）和非 ARB/ACEI 使用者（n=2487）每 100 人月发生 5.0 和 6.0 例主要结局（HR 0.85，95%置信区间 [CI] 0.73-0.99，中位随访 87 天）。在门诊患者中，ARB 使用者（n=4877）和 ACEI 使用者（n=8704）每 100 人月发生 13.2 和 14.8 例主要结局（HR 0.91，95%CI 0.86-0.97，中位随访 85 天）。在住院患者中，ARB/ACEI 使用者（n=210）和非 ARB/ACEI 使用者（n=275）每 100 人月发生 3.4 和 2.0 例全因死亡（HR 1.25，95%CI 0.30-5.13，中位随访 30 天）。在住院患者中，ARB 使用者（n=1164）和 ACEI 使用者（n=2014）每 100 人月发生 21.0 和 17.7 例全因死亡（HR 1.13，95%CI 0.93-1.38，中位随访 30 天）。
这项观察性分析支持在 SARS-CoV-2 感染前已使用这些药物的患者继续使用 ARB 或 ACEI。在门诊患者中，ARB 使用者与 ACEI 使用者之间观察到的有益关联应该通过随机试验得到证实。
