Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people
Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people
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DOI：
10.1136/heartjnl-2020-318312
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发表时间：
2020-10-01
期刊：
影响因子：
5.7
通讯作者：
Watkinson, Peter J.
中科院分区：
文献类型：
--
作者：
Hippisley-Cox, Julia;Young, Duncan;Watkinson, Peter J.
背景血管紧张酶（ACE）抑制剂和血管紧张素受体阻滞剂（ARB）药物与COVID-19疾病的相关性尚不确定。我们研究了服用这些药物的患者是否改变了感染COVID-19严重疾病和接受相关重症监护病房（ICU）住院的风险。方法：这是一项前瞻性队列研究，使用常规收集的数据来自英格兰1205个全科诊所，参与者828万，年龄在20-99岁之间。我们使用Cox比例风险模型，根据社会人口因素、同时使用的药物和地理区域，得出ACE抑制剂和ARB药物暴露的调整hr。主要结局为：(a) COVID-19 RT-PCR诊断疾病和(b) COVID-19疾病导致ICU护理。结果19 486例新冠肺炎患者中，1286例接受了ICU护理。在对多种混杂因素进行校正后，ACE抑制剂与COVID-19疾病的风险显著降低相关（调整后的HR 0.71, 95% CI 0.67至0.74），但未增加ICU护理的风险（调整后的HR 0.89, 95% CI 0.75至1.06）。COVID-19疾病arb的调整hr为0.63 (95% CI 0.59 ~ 0.67)， ICU护理的调整hr为1.02 （95% CI 0.83 ~ 1.25）。在COVID-19疾病中，种族、ACE抑制剂和arb之间存在显著的相互作用。与ACE抑制剂相关的COVID-19疾病风险在加勒比组（校正HR 1.05, 95% CI 0.87至1.28）和黑非洲组（校正HR 1.31, 95% CI 1.08至1.59）高于白人组（校正HR 0.66, 95% CI 0.63至0.70）。非洲黑人（校正后的风险比1.24,95% CI 0.99至1.58）比白人（校正后的风险比0.56,95% CI 0.52至0.62）组患COVID-19的风险更高。在对一系列变量进行调整后，ACE抑制剂和arb与COVID-19疾病风险降低相关。ACE抑制剂和arb均与接受ICU护理的风险显著增加无关。不同种族间的差异提示ACE抑制剂/ arb对COVID-19疾病易感性和严重程度的种族特异性作用的可能性，值得进一步研究。
Background There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.Methods This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20-99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.Findings Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.Interpretation ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.