Renin-angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis.
Renin-angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis.
复制标题
DOI：
10.1016/s2589-7500(20)30289-2
复制
发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Suchard MA
中科院分区：
文献类型：
--
作者：
Morales DR;Conover MM;You SC;Pratt N;Kostka K;Duarte-Salles T;Fernández-Bertolín S;Aragón M;DuVall SL;Lynch K;Falconer T;van Bochove K;Sung C;Matheny ME;Lambert CG;Nyberg F;Alshammari TM;Williams AE;Park RW;Weaver J;Sena AG;Schuemie MJ;Rijnbeek PR;Williams RD;Lane JCE;Prats-Uribe A;Zhang L;Areia C;Krumholz HM;Prieto-Alhambra D;Ryan PB;Hripcsak G;Suchard MA
血管紧张素转换酶抑制剂（ACEIs）和血管紧张素受体阻滞剂（ARBs）被认为会影响对COVID-19的易感性。迄今为止，观察性研究缺乏严格的确定、调整和国际通用性。我们的目的是确定使用acei或arb是否与高血压患者对COVID-19易感性增加有关。在这个国际开放科学的队列分析中，我们使用来自西班牙（初级保健研究信息系统[SIDIAP]）和美国（哥伦比亚大学欧文医学中心数据仓库[CUIMC]和退伍军人事务部观察性医疗结果合作伙伴关系[VA-OMOP]）的电子健康记录来识别年龄在18岁或以上且至少有一种acei和arb处方（目标队列）或钙通道阻滞剂（CCBs）和噻嗪类或噻嗪类利尿剂(THZs；比较队列)，于2019年11月1日至2020年1月31日期间进行。使用者被单独定义为接受这四种药物类别的单一治疗，或与其他抗高血压药物的单一治疗或联合治疗（联合使用）。我们评估了四个结局：COVID-19诊断；因COVID-19住院；因肺炎住院；并因肺炎、急性呼吸窘迫综合征、急性肾损伤或败血症入院。我们通过数据驱动的方法和10个两两比较的负对照实验建立了大规模倾向评分方法，并对结果进行了meta分析，产生了1280个研究效应。对于每个研究效果，我们使用通过数据丰富的算法确定的可能的123个对照进行了阴性对照结果实验。该过程使用一组预定义的基线患者特征，以提供最准确的治疗预测和患者队列之间跨特征的平衡。该研究已在欧盟授权后研究注册处注册，编号为EUPAS35296。在纳入分析的1 355 349名降压患者（363 785名ACEI或ARB单一治疗患者，248 915名CCB或太赫兹单一治疗患者，711 799名ACEI或ARB联合治疗患者，473 076名CCB或太赫兹联合治疗患者）中，与CCB或太赫兹单一治疗相比，ACEI或ARB单一治疗暴露与COVID-19诊断无相关性（校正风险比[HR] 0.98, 95% CI 0.84 -1·14）或联合使用暴露（1.01,0.90 -1·15）。与CCB或THZ单药相比，单独使用ACEIs同样没有相对风险差异（HR 0.91, 95% CI 0.68 - 1.21；异质性为0.40%）或联合使用（0.95,0.83 - 0.07）。直接比较acei与arb显示，acei的风险较低，联合使用时显著（HR 0.88, 95% CI 0.79 ~ 0.99），单药治疗时无显著差异（HR 0.85, 95% CI 0.69 ~ 1.05）。我们观察到，在所有比较中，不同药物类别对COVID-19住院风险、肺炎住院风险、肺炎住院风险、急性呼吸窘迫综合征、急性肾损伤或败血症住院风险无显著差异。未观察到与使用ACEI或ARB相关的COVID-19诊断风险或住院相关结局的临床显著增加，提示使用者不应停止或改变治疗以降低COVID-19的风险。惠康基金会、英国国立卫生研究院、美国国立卫生研究院、美国退伍军人事务部、杨森研发公司、IQVIA、韩国卫生福利部、澳大利亚国家卫生和医学研究委员会、欧洲卫生数据和证据网络。
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension. In this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296. Among 1 355 349 antihypertensive users (363 785 ACEI or ARB monotherapy users, 248 915 CCB or THZ monotherapy users, 711 799 ACEI or ARB combination users, and 473 076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84–1·14) or combination use exposure (1·01, 0·90–1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68–1·21; with heterogeneity of >40%) or combination use (0·95, 0·83–1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79–0·99) and non-significant for monotherapy (0·85, 0·69–1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons. No clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19. Wellcome Trust, UK National Institute for Health Research, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, South Korean Ministry of Health and Welfare Republic, Australian National Health and Medical Research Council, and European Health Data and Evidence Network.